Search

Purpose The use of nebulized opioids for the palliation of dyspnea in terminally ill patients is reviewed. Summary More than 50% of patients with advanced diseases experience dyspnea during their final stages of life. Systemically administered opioids are recommended for the management of dyspnea in these patients, but adverse effects may limit their use. Nebulization offers an alternative route for administering opioids, providing relief of dyspnea while minimizing adverse events. An extensive literature search was conducted to identify publications evaluating nebulized opioids for the palliation of dyspnea in patients at end-of-life. Ten studies that evaluated nebulized morphine, fentanyl, hydromorphone, and morphine-6-glucuronide were reviewed; 1 of these studies evaluated 4 different opioids. Of these 10 studies, 2 had double-blind, placebo-controlled, randomized crossover designs; 1 was retrospective, and the remaining 7 were prospective studies. A total of 181 patients, all adults, were evaluated. Subjective improvement in dyspnea from baseline was observed in 9 of the 10 studies. Nebulized morphine 20 mg every 4 hours was the most common opioid studied. Other doses of nebulized opioids included fentanyl 25 and 100 μg and hydromorphone 5 mg. Nine studies reported subjective improvement of dyspnea from baseline after administering nebulized opioids. Six studies evaluated objective outcomes and showed decreased respiratory rate (morphine, fentanyl, and hydromorphone) and heart rate (hydromorphone) and increased oxygen saturation (fentanyl). Mild-to-moderate adverse effects such as claustrophobia due to nebulizer mask, drowsiness, cough, and bitter taste were described. Conclusion Nebulized opioids may provide subjective relief of dyspnea in terminally ill patients with mild-to-moderate adverse effects.

Objectives To evaluate dosing alert appropriateness, categorize orders with alerts, and compare the appropriateness of alerts due to customized and non-customized dose ranges at a pediatric hospital. Methods This was a retrospective analysis of medication orders causing dosing alerts. Orders for outpatient prescriptions, patients ≥18 years of age, and research protocols were excluded. Patient medical records were reviewed and ordered doses compared with a widely used pediatric reference (Lexi-Comp) and institutional recommendations. The alerted orders were categorized and the occurrence of appropriate alerts was compared. Results There were 47 181 inpatient orders during the studied period; 1935 orders caused 3774 dosing alerts for 369 medications in 573 patients (median age 6.1 years). All alerted orders had an alert overridden by the prescriber. The majority (86.2%) of alerted orders inappropriately caused alerts; 58.0% were justifiable doses and 28.2% were within Lexi-Comp. However, 13.8% of alerted orders appropriately caused alerts; 8.0% were incorrect doses and 5.8% had no dosing recommendations available. Appropriately alerted orders occurred in 19.7% of alerted orders due to customized ranges compared to 12.8% due to non-customized ranges (p=0.002). Preterm and term neonates, infants, and children (2–5 years) had higher proportions of inappropriate alerts compared to appropriate alerts (all p

Purpose The use of intermittent i.v. sildenafil dosing in three patients with pulmonary hypertension (PH) and limited venous access is reported. Summary One preterm infant with PH in addition to bronchopulmonary dysplasia and two full-term neonates with PH after congenital diaphragmatic hernia repairs were successfully treated for PH with adjunctive intermittent i.v. sildenafil. sildenafil dosages ranged from 0.4 to 2 mg/kg every six hours. Infusion periods ranged from one to three hours. The longer infusion periods were used to minimize the risk of hypotension during infusion, with continued efficacy assessment between dosing intervals by monitoring ongoing oxygenation saturation trends and oxygen requirements when the drug was not infusing. Treatment duration ranged from 5 to 50 days. Decreases or fluctuations in systemic blood pressure were noted at the beginning of treatment, but minimal interventions were required to maintain blood pressure, which generally increased during extended treatment. Fraction of inspired oxygen requirements were decreased or remained stable during each patient’s first dose, and the need for respiratory support decreased over time, with improvements in oxygenation and prevention of continual life-threatening desaturation episodes. PH eventually resolved in each patient, based on improvements in serial echocardiographic studies with decreased requirements for inhaled nitric oxide, oxygen, and mechanical ventilation. All three patients required weaning from sildenafil treatment, suggesting a potential for rebound respiratory insufficiency with abrupt discontinuation of sildenafil. Conclusion Intermittent i.v. sildenafil dosing provided a well-tolerated, practical, and potentially effective treatment for PH in three patients when enteral intake was undesirable and when there was a need to conserve available venous access.

Background and objective Accurate and informed prescribing is essential to ensure the safe and effective use of medications in pediatric patients. Computerized clinical decision support (CCDS) functionalities have been embedded into computerized physician order entry systems with the aim of ensuring accurate and informed medication prescribing. Owing to a lack of comprehensive analysis of the existing literature, this review was undertaken to analyze the effect of CCDS implementation on medication prescribing and use in pediatrics. Materials and methods A literature search was performed using keywords in PubMed to identify research studies with outcomes related to the implementation of medication-related CCDS functionalities. Results and discussion Various CCDS functionalities have been implemented in pediatric patients leading to different results. Medication dosing calculators have decreased calculation errors. Alert-based CCDS functionalities, such as duplicate therapy and medication allergy checking, may generate excessive alerts. Medication interaction CCDS has been minimally studied in pediatrics. Medication dosing support has decreased adverse drug events, but has also been associated with high override rates. Use of medication order sets have improved guideline adherence. Guideline-based treatment recommendations generated by CCDS functionalities have had variable influence on appropriate medication use, with few studies available demonstrating improved patient outcomes due to CCDS use. Conclusion Although certain medication-related CCDS functionalities have shown benefit in medication prescribing for pediatric patients, others have resulted in high override rates and inconsistent or unknown impact on patient care. Further studies analyzing the effect of individual CCDS functionalities on safe and effective prescribing and medication use are required.

OBJECTIVES This study examined trends in physician-prescribing of medications for children with sleep difficulties in outpatient settings in the US. Additionally, we explored the incidence of physician prescribing patterns of medications with high abuse potential for children with sleep difficulties. METHODS A cross-sectional study was conducted on patients aged < or =17 years with sleep difficulties from 1993-2004 using data from the National Ambulatory Medical Care Survey (NAMCS). Office visits were considered related to sleep difficulties if relevant ICD-9 codes were recorded and if sleep difficulties were reported as the reason for the visits. Medications were retrieved using the NAMCS drug codes, and all analyses were weighted to determine national estimates. RESULTS During 1993 to 2004, approximately 18.6 million visits occurred for sleep related difficulty in children. The highest percentage of visits were by school-aged children (6 to 12 years). Pediatricians saw 35% of patients, psychiatrists saw 24%, and general/family practice physicians saw 13% of the patients. Eighty-one percent of visits among children with sleep difficulties resulted in a prescription for a medication. Many of these medications prescribed lack FDA approved labeling to assure their effectiveness and safety in this population. CONCLUSION The findings of this study suggest that physicians frequently prescribed medications for sleep difficulties in children in US outpatient settings. Of particular concern is prescribing of many unapproved medications for this population.

Purpose. The stability of sildenafil citrate 2.5 mg/mL in two extemporaneously prepared oral suspensions stored at 4 and 25 °C was studied. Methods. Thirty 25-mg tablets of sildenafil citrate were ground to powder, and the powder was combined with a 1:1 mixture of Ora-Sweet and Ora-Plus or a 1:1 mixture of methylcellulose 1% and Simple Syrup, NF, to produce two 2.5-mg/mL suspensions. Five plastic bottles of each suspension were stored in amber plastic prescription bottles at 4 or 25 °C. Samples were collected on days 0, 7, 14, 28, 42, 56, 70, and 91 for analysis of sildenafil content by high-performance liquid chromatography; pH was also measured. Samples were visually observed against black and white backgrounds. Results. The mean concentration of sildenafil citrate exceeded 98% of the initial concentration in all samples at both temperatures throughout the 91-day study period. No changes in pH, odor, or physical appearance were observed. Conclusion. Sildenafil citrate 2.5 mg/mL in two extemporaneously compounded oral suspensions was stable for 91 days in plastic prescription bottles at 4 and 25 °C.

Purpose. The development, implementation, and outcomes assessment of an innovative pharmacist-managed ambulatory care and community pharmacy practice clinic are described. Summary. The Clinical Partners Program at The Ohio State University (OSU) provides an active learning environment for students and residents, offers a patient-focused practice model based on pharmaceutical care principles, and serves as an arena for applied research in pharmacy practice. The program offers multiple services, including anticoagulation management, diabetes self-management, cholesterol management, hepatitis C education, herbal product and dietary supplement consultations, medication management, smoking cessation, and wellness. The practice is currently staffed by two faculty members from the college of pharmacy, with a 0.8 full-time-equivalent (FTE) pharmacist and a 0.65 FTE community pharmacy resident. It has served as a training site for 17 pharmacy residents, 28 bachelor of science (B.S.) in pharmacy students, 30 post-B.S. doctor of pharmacy (Pharm.D.) students, and 132 entry-level Pharm.D. students at various levels of training. The most successful methods of reimbursement for programs have been contracted services with OSU Managed Health Care Systems, Inc., which serves OSU faculty and staff and fee-for-service billing, charged directly to non-OSU patients. Numerous studies have shown that Clinical Partners has consistently demonstrated improved therapeutic outcomes over those achieved in traditional practice. Faculty are exploring outreach services, including the development of advanced practice community sites for the college, establishing patient care services within physician offices, and providing disease management services for self-insured employers. Conclusion. The Clinical Partners Program has improved patient care and provided education and training opportunities for pharmacy students and residents.

Background Patient weight and family history are significant risk factors for the development of hypertension in children. Multiple genetic factors have been identified in primary (essential) hypertension in adults; however, the delineation of genetic factors in the separate populations of children with primary or secondary hypertension are not well understood. Heritability is the proportion of observed variation in a particular trait that can be attributed to an inherited genetic factor in contrast to environmental factors. In the consideration of hypertension, heritability can be assessed in terms of an underlying continuous gradient of the liability for developing hypertension. With this assumption it is possible to compute heritability using hypertension incidence among relatives and described by Falconer. Heritability values range from 0 (no genetic contribution) to 1 (complete genetic contribution). The aim of this study was to determine the genetic contribution to primary and secondary hypertension in a pediatric population through heritability analysis. Methods This was a retrospective case-control analysis of medical records of children ( n = 276) followed in the Pediatric Nephrology Clinic over a 4-year period from 1999 to 2002. There were 192 children and adolescents with primary hypertension (124 male, 68 female, age 0 to 21 years) and 84 children and adolescents with secondary hypertension (46 male, 38 female, age 0 to 21 years). Each hypertensive group served as the control for the other. Estimates of heritability were made using Falconer’s method 2. 11 The model assumes independence between the environment and genetic factors and that the joint distribution of liabilities between parent and child are normally distributed. Problems can arise from computing heritability due to dominance within loci, correlations between nongenetic familial effects, or the presence of a major gene. Results Of the children and adolescents with primary hypertension, 49% had parents with primary hypertension; and of the children and adolescents with secondary hypertension, 24% had parents with primary hypertension. Of the children and adolescents with primary hypertension, 10% had parents with secondary hypertension; and of the children and adolescents with secondary hypertension, 46% had parents with secondary hypertension. The estimated heritability for primary hypertension was 0.84 (SE = 0.21). The estimated heritability for secondary hypertension was 1.14 (SE = 0.21). As the value was >1, this indicates that the fit of the liability model is poor and that a few genes, or even one major gene, were significantly involved in the causes of secondary hypertension in the children and adolescents studied. Conclusions The results suggest that primary and secondary hypertension do not share the same type of genetic profile. Primary hypertension in children and adolescents is likely due to a large number of additive contributions of genes, although a highly correlated environmental component can not be excluded. The continuous liability model is inappropriate for secondary hypertension because the estimate was substantially greater than one. This study supports the model that secondary hypertension in children and adolescents may be related to just a few genes.

The efficacy, safety, administration, and advantages and disadvantages of respiratory syncytial virus (RSV) immune globulin and palivizumab for preventing RSV infection are discussed. Prevention of RSV infection has attracted considerable attention because of its dinical and economic impact. Studies have shown respiratory syncytial virus immune globulin intravenous (RSV-IGIV) and palivizumab to be effective in decreasing the number of hospitalizations and hospital days attributable to RSV. The number of intensive-care-unit admissions and the severity of RSV infection in high-risk children decreased with the use of these agents. Both agents have been well tolerated, with few adverse effects; however, their high cost necessitates strict guidelines on use. The patient populations at greatest risk are those with bronchopulmonary dysplasia, those with congenital heart disease, those with a history of apnea or respiratory arrest, immunocompromised patients, those with pulmonary consolidation on chest radiography, and those born prematurely. American Academy of Pediatrics guidelines do not preferentially recommend use of either agent; each has advantages and disadvantages. Prophylactic therapy with RSV-IGIV or palivizumab may reduce the likelihood of RSV infection in high-risk patients.

Purpose. The stability of iobenguane sulfate stored at 4–7 °C over 91 days was studied. Methods. An iobenguane sulfate solution at a concentration of 2.2 mg/mL was prepared in a top-fill i.v. bag using 143 mg of iobenguane sulfate and 65 mL of Sterile Water for Injection, USP. The solution was poured through a 0.22- μm filter assembly for sterilization into 60 1-mL polycarbonate plastic syringes. Each syringe was filled with 0.9 mL of the iobenguane sulfate solution and stored in amber plastic bags at 4–7 °C. The stability of iobenguane sulfate was analyzed using high-performance liquid chromatography immediately after solution preparation and on days 7, 14, 28, 42, 56, 70, and 91. Samples were inspected for chemical purity by observing for particulate formation and color change. Results. The mean concentration of ioben-guane exceeded 93% of the initial concentration in all samples throughout the 91-day study period. No changes in color or turbidity were observed. Conclusion. Iobenguane sulfate 2.2 mg/mL was stable for 91 days when stored in polycarbonate syringes at 4–7 °C.

The stability of fumagillin 70 microg/mL (as the bicyclohexylammonium crystal) in an extemporaneously prepared ophthalmic solution was studied. An ophthalmic solution of fumagillin 70 microg/mL was prepared by combining 120 mg of fumagillin bicyclohexylammonium crystals with 20 mL of 0.9% Sodium Chloride Injection, USP, and 20 mL of an ophthalmic irrigating solution. The solution was stored in 12 sterile semi-opaque dropper bottles; 4 bottles were stored at 25 degrees C exposed to light, 4 were stored at 25 degrees C in the dark, and 4 were stored at 4 degrees C in the dark. Samples were taken on days 0, 7, 14, 21, and 28 and analyzed by high-performance liquid chromatography. Sterility was tested as well. In the solutions stored at 25 degrees C, 17-30% of the initial drug concentration was lost during the first week. The solution protected from light and stored at 4 degrees C lost about 12% of active drug by week 4. There was no change in color or odor in any of the solutions and only a minor change in pH over the study period. There was no evidence of microbial growth in any of the solutions tested. Fumagillin 70 microg/mL (as the bicyclohexylammonium crystal) in 0.9% sodium chloride injection and an ophthalmic irrigating solution containing benzalkonium chloride was stable in the dark for 14 days at 4 degrees C.

The pathogenesis, epidemiology, clinical features, sequelae, and treatment of bronchiolitis are reviewed. Acute bronchiolitis is the most common severe lower-respiratory-tract infection of infancy. During epidemics, more than 80% of cases may be caused by respiratory syncytial virus (RSV). Although signs and symptoms may become severe, most infections are self-limited and improvement occurs within several days. Approximately 1-2% of infants less than one year of age require hospitalization. Generally, patients who develop severe, life-threatening RSV bronchiolitis are those with underlying cardiopulmonary disease, immunosuppression, bronchopulmonary dysplasia, or a history of premature birth. In severe bronchiolitis, necrosis of the respiratory epithelium, excessive mucus production, and lymphocytic infiltration result in edema, dense plugs of debris, and subsequent bronchiolar obstruction. IgE-mediated reactions and release of inflammatory mediators may result in exacerbation of acute obstruction and may contribute to chronic obstructive pulmonary dysfunction, a common sequela of bronchiolitis. Patients hospitalized with bronchiolitis usually require supportive therapy and may require mechanical ventilation. Based on recent data, a trial of aerosolized beta 2 agonists is warranted in all patients. Systemic corticosteroids have not proved efficacious and have a limited role in the treatment of acute bronchiolitis. Inhaled corticosteroids may be useful in reducing the severity of chronic wheezing that may follow acute bronchiolitis. Ribavirin may be considered in patients with severe illness or in those at high risk for severe RSV disease. Intravenous immune globulin may have a role in the treatment of lower-respiratory-tract infections involving RSV; however, since few studies have been performed in humans, it is not possible to determine its place in the treatment of bronchiolitis. A trial of aerosolized beta 2 agonists is warranted in patients with bronchiolitis. Ribavirin may be considered in patients with severe disease or those at high risk for severe disease.

The stability of propylthiouracil in two extemporaneously prepared suspensions at 4 and 25 degrees C was studied. Commercially available 50-mg propylthiouracil tablets were used to prepare suspensions in 1:1 Ora-Sweet:Ora-Plus and in 1:1 1% methylcellulose:Simple Syrup, NF, to yield a propylthiouracil concentration of 5 mg/mL. Each suspension was stored in 10 amber plastic prescription bottles, 5 of them at 4 degrees C and the other 5 at 25 degrees C. Three samples were taken from each bottle at 0, 7, 14, 28, 42, 56, 70, and 91 days for assay by stability-indicating high-performance liquid chromatography. More than 90% of the initial propylthiouracil concentration was retained in both suspensions for 70 days at 25 degrees C and for 91 days at 4 degrees C. There were no changes in physical appearance, color, or odor, and the pH remained essentially unchanged. Propylthiouracil 5 mg/mL in two extemporaneously prepared oral suspensions was stable for at least 70 days at 25 degrees C and for at least 91 days at 4 degrees C.

The pharmacokinetics, pharmacodynamics, and clinical uses of fentanyl, sufentanil, and alfentanil are reviewed. The fentanyl derivatives have reduced or eliminated many of the disadvantages of opioid anesthetics, such as incomplete amnesia and undesirable hemodynamic responses to surgery. Fentanyl is 50-100 times as potent as morphine and was the first of the three to be marketed. Sufentanil is even more potent than fentanyl. Alfentanil has the fastest onset of action, followed by sufentanil and then fentanyl. Alfentanil also has the shortest duration of action of the group. Most studies of these agents have been done to assess their role as anesthetics in cardiac surgery. All three provide cardiovascular stability when administered before noxious surgical stimuli, except when given as a single bolus during the induction of anesthesia. All seem to produce adequate anesthesia, particularly when used in combination with nitrous oxide. Because of its short duration of action, alfentanil is preferred for brief procedures or when rapid changes in the level of consciousness are desired. All three agents have also been used for analgesia; epidural administration provides adequate relief of pain. Fentanyl has been formulated as a transdermal patch that seems to provide the same degree of analgesia as a continuous i.v. infusion. Fentanyl has also been formulated as an investigational lozenge that has shown advantages as a preoperative sedative in children. As more is learned about these agents, their perioperative uses for anesthesia, analgesia, and sedation will continue to be refined.

The stability of cefotaxime sodium at room and body temperatures in peritoneal dialysis solutions containing 1.5% or 4.25% dextrose was determined. Cefotaxime sodium 2 g was added to three 2-L bags of dialysis solution containing 1.5% dextrose, and cefotaxime sodium 500 mg was added to three 500-mL bags of dialysis solution containing 4.25% dextrose. The bags were stored at 25 or 37 degrees C Samples from bags stored at 25 degrees C were drawn aseptically at 0, 12, 24, 48, and 72 hours, and samples from bags stored at 37 degrees C were drawn at 0, 6, 12, and 24 hours. The pH of each sample was determined, and the cefotaxime concentration was measured by a stability-indicating high-performance liquid chromatographic method. At 37 degrees C the initial mean cefotaxime concentration declined to 97.9% at six hours, 89.1% at 12 hours, and 68.8% at 24 hours in the 1.5% dextrose solution; the mean percentages remaining in the solution containing 4.25% dextrose were 96.4%, 86.1%, and 71.0% at 6, 12, and 24 hours, respectively. At 25 degrees C the initial cefotaxime concentration declined to 92.4%, 84.4%, and 74.2% at 24, 48, and 72 hours, respectively, in 1.5% dextrose solution and to 92.0%, 84.3%, and 80.3% at 24, 48, and 72 hours, respectively, in 4.25% dextrose solution. In both solutions, cefotaxime concentration decreased by more than 10% at and after 12 hours at 37 degrees C and between 24 and 48 hours at 25 degrees C.(ABSTRACT TRUNCATED AT 250 WORDS)

The stability of terbinafine 25 mg/mL (as the hydrochloride salt) in an extemporaneously prepared oral suspension at 25 and 4 degrees C was studied. Twenty 250-mg terbinafine tablets were crushed to a fine powder and diluted to a concentration of 25 mg/mL with sweetened vehicle. The suspension was stored in amber polyethylene prescription bottles at 25 or 4 degrees C. Samples were taken on days 0, 7, 14, 28, 42, 56, 70, and 91 for duplicate analysis of terbinafine content by high-performance liquid chromatography and to observe any changes in color and odor; pH was measured as well. Through the initial 42 days, the mean concentration of terbinafine in the samples stored at both temperatures was >93% of the initial concentration; by day 56, the mean concentration was

The stability of pyrimethamine in a liquid dosage formulation stored for up to three months was studies. Commercially available 25-mg pyrimethamine tablets were crushed with a mortar and pestle and mixed with a 1:1 mixture of Simple Syrup, NF, and 1% methylcellulose to yield a suspension with a pyrimethamine concentration of 2 mg/mL. The suspension was poured into 10 amber plastic and 10 amber glass prescription bottles; 5 plastic and 5 glass bottles were stored at 4 degrees C, and the remaining bottles were kept at 25 degrees C. Samples were collected at intervals up to 91 days and tested for pyrimethamine concentration by stability-indicating high-performance liquid chromatography. Pyrimethamine remained stable throughout the three-month study period under all conditions. At 4 degrees C, pyrimethamine concentrations remained above 96% of the initial concentration; at 25 degrees C, pyrimethamine concentrations remained above 91%. No substantial changes in pH were observed. Pyrimethamine was stable for at least 91 days in an oral suspension stored in plastic or glass prescription bottles at 4 or 25 degrees C.

The stability of pentoxifylline in an extemporaneously prepared suspension was studied. Twelve 400-mg pentoxifylline tablets were crushed and mixed with water to prepare a 20-mg/mL suspension. The suspension was transferred to 10 amber glass and 10 amber plastic prescription bottles. Five glass and five plastic bottles were stored at 25 degrees C, and the rest were stored at 4 degrees C. Samples were collected before storage and on days 7, 14, 21, 28, 42, 56, 70, and 91 and analyzed in duplicate by stability-indicating reverse-phase high-performance liquid chromatography. Pentoxifylline was stable in the suspension under all storage conditions for the duration of the study. The color, odor, and pH of the suspension did not change appreciably. Some settling of the suspension was noted in all bottles beginning on day 21, but shaking resuspended the settled material. Pentoxifylline 20 mg/mL was stable in an extemporaneously prepared suspension for at least 91 days at 25 or 4 degrees C.

The stability of flucytosine in an oral liquid prepared from capsules was studied. Flucytosine 10-mg/ml oral liquid was prepared from 500-mg capsules (with distilled water as the diluent) and transferred to 10 glass and 10 plastic amber bottles. Five of each type of bottle were stored at 4 degrees C and five of each at 25 degrees C. Samples were taken at 0, 7, 14, 28, 42, 56, 70, and 91 days, and flucytosine concentration was measured by stability-indicating high-performance liquid chromatography. Flucytosine was stable in the liquid formulation for at least 70 days under all the study conditions. The physical appearance of the liquid stored at 4 degrees C did not change during the study period. Flocculation was observed both in glass and in plastic bottles stored at 25 degrees C on day 14 and thereafter. Flucytosine 10 mg/mL in an extemporaneously prepared oral liquid was stable for 70 days in glass or plastic prescription bottles kept at 4 or 25 degrees C.

The stability of ceftazidime (with arginine) stored in plastic syringes at three temperatures was studied. Ceftazidime (with arginine) was reconstituted with sterile water for injection to a concentration of 100 mg/mL and transferred to plastic syringes. Syringes were stored at 22 degrees C for 24 hours; at 4 degrees C for 7 or 10 days, then at 22 degrees C for 24 hours; or at -20 degrees C for 91 days, then at 22 degrees C for 24 hours or at 4 degrees C for seven days followed by 22 degrees C for 24 hours. Ceftazidime concentration was measured at various times by using a stability-indicating high-performance liquid chromatographic method. At each sampling time, each syringe was visually inspected and the pH of each solution was measured. Mean ceftazidime concentration remained > 90% of initial concentration at all storage conditions. Although during storage the color of the solutions changed from light straw to dark yellow and the pH decreased, no precipitate was visually detected and no peaks for degradation products appeared on the chromatograms. Ceftazidime 100 mg/mL (with arginine) in sterile water for injection was stable when stored in plastic syringes for up to 24 hours at 22 degrees C, for 10 days at 4 degrees C followed by up to 24 hours at 22 degrees C, and for 91 days at -20 degrees C followed by up to 24 hours at 22 degrees C or by 7 days at 4 degrees C and up to 24 hours at 22 degrees C.

The stability of cefazolin sodium was studied in two commonly used peritoneal dialysis solutions. Cefazolin (as the sodium salt) 250 mg was added to 500-mL bags of dialysis solution containing 1.5% or 4.25% dextrose injection to yield a target concentration of 0.5 mg/mL. Of 18 bags containing 1.5% dextrose injection, six were stored at 4 degrees C, six at 25 degrees C, and six at 37 degrees C. Similarly, of 18 bags containing 4.25% dextrose injection, groups of six were stored at each temperature. Samples were measured for cefazolin concentration by high-performance liquid chromatography at 0, 3, 7, 10, and 14 days for solutions stored at 4 degrees C; 0, 1, 2, 3, 8, and 11 days for solutions stored at 25 degrees C; and 0, 6, 12, and 24 hours for solutions stored at 37 degrees C. The cefazolin concentration in both solutions was greater than or equal to 90% of the initial concentration for 14 days at 4 degrees C, 8 days at 25 degrees C, and 1 day at 37 degrees C. On day 11 at 25 degrees C, however, the loss of cefazolin was 11% for the solution containing 1.5% dextrose injection and 15% for the 4.25% dextrose injection. The sterility of the solutions was not determined. Cefazolin sodium was stable in peritoneal dialysis solutions containing 1.5% and 4.24% dextrose injection for 14 days at 4 degrees C, 8 days at 25 degrees C, and 24 hours at 37 degrees C.

The incidence, pathophysiology, and clinical findings of symptomatic patent ductus arteriosus (PDA) are reviewed, and the pharmacologic management of symptomatic PDA is discussed. Spontaneous closure of the ductus arteriosus (DA) usually occurs within four days after birth in most premature and full-term infants. The incidence of PDA is related to birth weight in premature infants and has been shown to decrease with an increase in birth weight. Clinical findings are reviewed. Prophylactic treatment in the first few hours after birth may not be needed in most premature infants. Treatment should be considered only if the ductus becomes symptomatic. Medical management consists of respiratory support, fluid restriction, diuretics, digoxin, and indomethacin. Respiratory support, fluid restriction, and diuretics are used as first-line treatment of symptomatic PDA. Digoxin cannot be recommended as part of first-line therapy, since its risks seem to outweigh the benefits in preterm infants. Indomethacin should be used only if other standard measures including fluid restriction and diuretic treatment fail. The mechanism of action, pharmacokinetics, adverse effects, and drug interactions of indomethacin are discussed. Symptomatic PDA can increase morbidity and mortality, especially in very low birth weight infants. Treatment of symptomatic PDA may decrease the morbidity associated with this condition.

The effects of gestational age and birth weight on tobramycin kinetics were studied in 26 newborn infants with presumed or proven bacterial sepsis during the first week of postnatal age. The infants received tobramycin, 2.5 mg/kg intravenously every 12 h. Group A consisted of nine patients 28 to 30 weeks of gestational age; group B had 11 patients greater than 30 to less than or equal to 34 weeks of gestational age; and group C had six patients greater than 34 to less than or equal to 40 weeks of gestational age. Steady-state peak serum concentrations of tobramycin averaged 6.5, 7.2 and 7.1 mg/l in groups A, B and C; the corresponding trough concentration averaged 2.0, 2.3 and 1.3 mg/l. The frequency of tobramycin trough serum concentration above 2 mg/l was 44% in group A, 45% in group B and 0% in group C. Total body clearance of tobramycin averaged 1.04, 1.13 and 1.28 ml/min/kg; apparent volume of distribution averaged 0.84, 0.81 and 0.61 l/kg; and elimination half-life averaged 9.3, 8.9 and 5.6 h in groups A, B and C. Group M consisted of seven infants with 1.0-1.25 kg birth weight; group N had six infants 1.26-1.50 kg birth weight; group O had seven infants 1.51-2.0 kg birth weight; and group P had six infants 2.1-3.5 kg birth weight. Steady-state peak serum concentration of tobramycin averaged 5.7, 7.3, 7.8 and 7.1 mg/l; and the trough serum concentration averaged 2.2, 2.4, 1.9 and 1.3 mg/l in groups M, N, O and P.(ABSTRACT TRUNCATED AT 250 WORDS)

The influence of primary fluids and dilutional volumes on the accuracy of in vitro delivery of cefazolin sodium by gravity flow through a new controlled-release membrane infusion device was studied. For primary fluid studies, cefazolin 1 g (as the sodium salt) in 10 mL of sterile water for injection was injected into the drug chamber, which is separated by a membrane from the fluid chamber; the entire dose passes into the fluid chamber over a set time. The inlet port of the fluid chamber was connected to the 1-L primary fluid bag, and the outlet port was connected to an administration set. The primary fluids included 0.9% sodium chloride injection; 5% dextrose injection; 10% dextrose injection; 5% dextrose and 0.45% sodium chloride injection; 5% dextrose, 0.45% sodium chloride, and potassium chloride 20 meq/L injection; and 2.2% amino acids with electrolytes in 25% dextrose injection. For dilutional volume studies, cefazolin sodium 1 g diluted in 5, 10, and 15 mL of sterile water for injection was infused with 0.9% sodium chloride injection. The flow rate was set at 1 mL/min. Serial samples were collected in triplicate every five minutes over a 90-minute period and analyzed by high-performance liquid chromatography. The time needed to deliver more than 95% of the cefazolin doses ranged from 35 to 50 minutes using various primary fluids and from 35 to 55 minutes using various dilutional volumes. The manufacturer recommends that a cefazolin dose be delivered completely within 30-60 minutes. The solutes in the primary fluids and the volume injected did not appear to affect the delivery of cefazolin by a controlled-release membrane device.

The stability of vancomycin hydrochloride in plastic syringes containing high concentrations of dextrose injection after storage for 24 hours in a refrigerator followed by storage for two hours at room temperature was studied. Vancomycin hydrochloride was reconstituted with sterile water for injection to a concentration of 50 mg/mL. One-milliliter samples were added to 9 mL of various concentrations of dextrose injection (5, 10, 15, 20, 25, and 30%) in 10-mL plastic syringes. Ten syringes of each concentration were stored at 4 degrees C for 24 hours. At various storage times, samples were assayed in triplicate for vancomycin using high-performance liquid chromatography. After 24 hours, the syringes were removed from the refrigerator, and the vancomycin concentration was determined after storage for two hours at room temperature. Percent change in vancomycin concentration during storage for 24 hours was less than 6% in all cases except for 5% dextrose injection at 4 and 24 hours. Vancomycin concentration did not change (percent change 0.7-5%) during storage for two hours at room temperature. Vancomycin hydrochloride is stable in various concentrations of dextrose injection when stored in plastic syringes for 24 hours in the refrigerator followed by two hours at room temperature.

The effects of flow rate and drug concentration on the accuracy of in vitro delivery of cefazolin, chloramphenicol, and vancomycin by a new controlled-release membrane infusion device, MICROS, were studied. Cefazolin, chloramphenicol, and vancomycin 1 g in sterile water for injection 10 mL were injected into the drug chamber of the device and delivered through an administration set with 0.9% sodium chloride injection from a primary line. Drug delivery was studied at four flow rates (0.5, 1.0, 1.5, and 2.0 mL/min). In addition, three concentrations of each drug (25, 50, and 100 mg/mL for cefazolin and vancomycin, and 50, 100, and 200 mg/mL for chloramphenicol) were studied at a fixed flow rate of 1 mL/min. Samples were collected in triplicate every 2.5-5.0 minutes using a fraction collector over a 90-minute period for cefazolin and a 120-minute period for chloramphenicol and vancomycin. The concentration of each drug was measured by high-performance liquid chromatography. At various flow rates, the time for delivery of greater than or equal to 95% of each dose ranged from 30 to 55 minutes for cefazolin, 45 to 70 minutes for chloramphenicol, and 50 to 65 minutes for vancomycin. At various concentrations, greater than or equal to 95% of each dose was delivered in 40 to 55 minutes for cefazolin, 40 to 70 minutes for chloramphenicol, and 50 to 60 minutes for vancomycin. The desired delivery times were 30-60 minutes for cefazolin and chloramphenicol and 50-70 minutes for vancomycin. Delivery of cefazolin and vancomycin by the MICROS membrane infusion system was accurate. Some delay was encountered in the delivery of chloramphenicol.(ABSTRACT TRUNCATED AT 250 WORDS)

The stability of phenobarbital sodium diluted to 10 mg/mL in 0.9% sodium chloride injection was studied at an unadjusted pH (8.5) and an adjusted pH (10.0) at 4 degrees C over a four-week period. The phenobarbital concentrations were measured before dilution and at 1, 2, 3, 7, 14, and 28 days using high-performance liquid chromatography. The observed phenobarbital concentrations ranged from 98.0 to 106.0% of initial concentration at the unadjusted pH and from 96.7 to 108.5% of initial concentration at the adjusted pH. The diluted phenobarbital sodium was stable over a four-week period at 4 degrees C without the need for pH adjustment.