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Background The family caregivers of patients with heart failure (HF) report burden and poor quality of life, but little is known about changes in their perceptions over time. Objectives The aims of this study were (1) to evaluate changes in caregiver burden (perceived time spent and difficulty with caregiving tasks), perceived control, depressive symptoms, anxiety, perceived life changes, and physical and emotional health-related quality of life; (2) to determine differences in perceptions between caregivers of patients with low HF symptoms (New York Heart Association class I and II) and caregivers of patients with high HF symptoms (New York Heart Association class III and IV); and (3) to the estimate time spent performing caregiving tasks. Methods Sixty-three HF patients and 63 family caregivers were enrolled; 53 caregivers completed the longitudinal study. Data were collected from medical records and interviews conducted by advanced practice nurses at baseline and 4 and 8 months later. Results Caregivers who completed the study had significant improvements in perceived time spent on and difficulty of caregiving tasks from baseline to 4 and 8 months, and depressive symptoms decreased from baseline to 8 months. Perceived life changes resulting from caregiving became more positive from baseline to 4 and 8 months. Perceived control, anxiety, and health-related quality of life did not change. Compared with caregivers of patients with low symptoms, caregivers of patients with high symptoms perceived that they spent more time on tasks and that tasks were more difficult, had higher anxiety, and had poorer physical health-related quality of life. Estimated time in hours spent providing care was high. Conclusions In this sample, perceptions of the caregiving experience improved over 8 months. Health-related quality of life was moderately poor over the 8 months. Caregivers of patients with more severe HF symptoms may be particularly in need of interventions to reduce time and difficulty of caregiving tasks and improve physical health-related quality of life.

Background Patients with chronic heart failure (HF) have cognitive deficits in memory, psychomotor speed, and executive function and poor health-related quality of life (HRQL), but the association between cognitive deficits and HRQL is unknown. Objectives The objectives of this study were to (1) evaluate the relationship between HF severity, age, comorbidities, and cognitive deficits and HRQL among patients with chronic HF and (2) examine whether cognitive deficits mediated the relationship between HF severity and HRQL. Design and sample This study was part of a larger explanatory study; 249 patients with HF completed face-to-face interviews. Methods Measures of HF severity, comorbidity (multiple comorbid conditions, hypertension, and depressive symptoms), cognitive function (domains of language, working memory, memory, psychomotor speed, and executive function), and HRQL were obtained. Clinical variables were abstracted from patients' records. Statistical analyses were conducted using descriptive statistics, Pearson correlation coefficients, and multiple linear regression analyses. Results Overall, the HRQL of patients was moderately poor. Heart failure severity, age, depressive symptoms, and total recall memory explained 55% of the variance in HRQL, but the contribution of memory was minimal (1%). Patients with more severe HF, younger age, and more depressive symptoms had poorer HRQL. Other cognitive function variables, multiple comorbidity, and hypertension were not significant explanatory variables for HRQL. Cognitive deficits did not mediate the relationship between HF severity and HRQL. Conclusions Novel interventions targeted at improving HRQL continue to be urgently needed, particularly among younger patients and patients with depressive symptoms. Measures of HRQL are not sufficient as outcomes when investigating cognitive deficits in HF. Investigators need to include outcome measures of patients' actual abilities to perform daily activities and HF self-care.

► Background: Patients with heart failure (HF) have been found to have cognitive deficits, but it remains unclear whether these deficits are associated with HF or with aging or comorbid conditions common in HF. ► Objectives: The purpose of this study was (a) to determine the types, the frequency, and the severity of cognitive deficits among patients with chronic HF compared with age-and education-matched healthy participants and participants with major medical conditions other than HF, and (b) to evaluate the relationships between HF severity, age, and comorbidities and cognitive deficits. ► Methods: A sample of 414 participants completed the study (249 HF patients, 63 healthy and 102 medical participants). The HF patients completed measures of HF severity, comorbidity (multiple comorbidity, depressive symptoms), and neuropsychological functioning. Blood pressure and oxygen saturation were assessed at interview; clinical variables were abstracted from records. Participants in the comparison groups completed the same measures as the HF patients except those specific to HF. ► Results: Compared with the healthy and medical participants, HF patients had poorer memory, psychomotor speed, and executive function. Significantly more HF patients (24%) had deficits in three or more domains. Higher (worse) HF severity was associated with more cognitive deficits; HF severity interacted with age to explain deficits in executive function. Surprisingly, men with HF had poorer memory, psychomotor speed, and visuospatial recall ability than women. Multiple comorbidity, hypertension, depressive symptoms, and medications were not associated with cognitive deficits in this sample. ► Discussion: HF results in losses in memory, psychomotor speed, and executive function in almost one fourth of patients. Patients with more severe HF are at risk for cognitive deficits. Older patients with more severe HF may have more problems in executive function, and men with HF may be at increased risk for cognitive deficits. Studies are urgently needed to identify the mechanisms for the cognitive deficits in HF and to test innovative interventions to prevent cognitive loss and decline.

BACKGROUND Patients with implantable cardioverter-defibrillators (ICDs) face problems in physical function, but little is known about how mastery predicts physical function over time. PURPOSE The primary purpose of this study was to examine the influence of mastery (assessed at baseline) on physical function (observed distance walked and perceived function) over 12 months among ICD patients. Secondary purposes were to (1) examine the influence of aging, in interaction with mastery, on physical function and (2) determine predictors of 12-month physical function. METHODS The ICD patients (N = 122; 75% men; 88% white; mean age, 65 years) completed the baseline interviews; 100 patients completed the 12-month interviews. Repeated-measures 1-way analyses of variance were used to examine the influence of mastery and the interaction of mastery and aging on physical function over 12 months. Multiple regression analyses were conducted to determine predictors of 12-month physical function. RESULTS The ICD patients with higher mastery had better walk distances than those with lower mastery; and walk distances were improved over 12 months, but only in those with lower mastery (F = 5.40, P = .02). The ICD patients with higher mastery had better perceived physical function than those with lower mastery (F = 25.57, P < .0001), but those with both lower and higher mastery did not show significant improvement. Neither significant interaction of aging and mastery on physical function nor predictors of walk distances were found. Baseline depression significantly predicted 12-month perceived physical function (F = 8.94, P = .0042). CONCLUSIONS The ICD patients with lower mastery had considerable impairments in physical function compared with those with higher mastery over time. Depression is more likely to predict perceived physical function. Further prospective studies are needed to validate these findings in a larger sample and develop interventions to improve physical impairment in ICD patients.

PURPOSE To elucidate the experience of fathers living with a colicky infant. STUDY DESIGN AND METHODS Interpretive phenomenology using in-depth interviews with 10 fathers of colicky infants. Reiterative interview reading, repeated meaning unit sorting, going back to the literature, and discussions gave way to emerging themes. FINDINGS The overall experience is one of "falling into and arising from the crying abyss together as a family." Four themes emerged: (a) falling in, (b) hitting bottom, (c) weaving strands to make a rope, and (d) climbing out. CLINICAL IMPLICATIONS From their stories, fathers provide insight useful to nurses assisting families of colicky infants through a very difficult time. Nurses should talk to fathers directly about the possibility of colic, and teach both parents what it is, how long it usually lasts, and what can be done about it. Anticipatory guidance as well as discussion about colic during newborn health visits can help parents to vocalize their feelings, and learn what actions to take when the stress of colic becomes overwhelming.

The prevalence of diabetes and related complications are disproportionally higher in Native Americans. Diabetes self-management (DSM) is instrumental in preventing complications. The results presented here are a part of a larger hermeneutic phenomenology study to explore living with diabetes for one Pacific Northwest tribe. This study identified barriers to DSM within the worldview of the tribal people. Using purposive sampling, 10 Coeur d’Alene tribal members, ages 26 to 86 years, participated in in-depth interviews. Data interpretation used a three-step method leading to integrated themes across the transcripts. Perceived unsatisfactory care emerged as the major barrier to self-management, including communication barriers (distrust, misunderstanding, and educational methods) and organizational barriers (quality of care and access issues). Findings highlight the need to improve cross-cultural communication and calls for different approaches to diabetes education. Our profession is challenged to create new DSM and diabetes educational approaches for acceptable and compassionate cross-cultural nursing care.

To test the hypothesis that renal failure has no effect on the pharmacokinetics of glyburide, five subjects with non-insulin-dependent diabetes mellitus (NIDDM) and end-stage renal disease requiring hemodialysis, and four NIDDM subjects with normal renal function were studied. On days 0, 1, and 15, subjects consumed 33 carbohydrate grams, and glucose, insulin, and C-peptide were measured for 4 hours. On day 1, subjects received 3 mg glyburide and measured plasma concentrations for 48 hours. On day 3, multiple dosing on 3 mg glyburide daily began. On day 15, plasma concentrations were measured for 48 hours. The pharmacokinetics and pharmacodynamics of glyburide, glucose, insulin, and C-peptide were determined as well as daily fasting blood glucose. Glucose area under the curve (AUC) and daily fasting glucose levels did not change in either controls or hemodialysis subjects. The mean serum glyburide blood levels and pharmacokinetics did not differ after initial or chronic glyburide administration in NIDDM subjects with end-stage renal disease treated with hemodialysis compared with controls. Glyburide half-life averaged 3.3 hours in control subjects and 5.0 hours in hemodialysis subjects. Hemodialysis subjects had increased C-peptide and insulin AUC with chronic dosing. Renal failure does not affect the pharmacokinetics of 3.0 mg oral glyburide.

Background Patients with chronic heart failure (HF) have impairment in memory, psychomotor speed, and executive function. Objective The aim of this study was to describe how individuals with HF and cognitive deficits manage self-care in their daily lives. Methods Using an interpretive phenomenology method, HF patients completed unstructured face-to-face interviews about their ability to manage complex health regimens and maintain their health-related quality of life. Analysis of data was aided by use of Atlas.ti computer software. Results The sample consisted of 12 patients (10 men; aged 43-81 years) who had previously undergone neuropsychological testing and were found to have deficits in 3 or more cognitive domains. Patients confirmed that they followed the advice of healthcare providers by adherence to medication regimens, dietary sodium restrictions, and HF self-care. One overarching theme was identified: "Re-cognition of Vulnerability: A Strange New World." This theme was further differentiated into 3 components: (1) not recognizing cognitive deficits; (2) recognizing cognitive deficits, described as (a) never could remember anything, (b) just old age, (c) HF-related change, and (d) making normal accommodations; and (3) recognizing vulnerability, explained by perception of (a) cognitive, (b) physical, and (c) social vulnerabilities, as well as perception of (d) the nearness of death. Discussion Although the study was designed to focus on the cognitive changes in HF patients, it was difficult to separate cognitive, physical, and social challenges. These changes are most useful when taken as a constellation. Healthcare professionals can use the knowledge to identify problems and interventions for HF patients.

Heart failure continues to be a major public health problem in the United States, with more than 5 million diagnoses of heart failure and nearly 500,000 new cases reported annually.1 The 12-month mortality rate is 10% to 20% for all patients with heart failure and 50% for patients with advanced, or New York Heart Association class IV, heart failure.1 Heart failure is a leading cause of hospitalization for elderly patients and costs millions of dollars in health care annually.1 Importantly, the health-related quality of life (HRQL) of these patients is poor because of the many troublesome signs and symptoms they experience.2–6 To improve survival, enhance HRQL, and reduce costly hospitalizations, patients with heart failure must adhere to complex medication, dietary, and self-care regimens; this adherence often requires the assistance of the patients’ family caregivers.7,8 Most of the care provided to patients with major chronic illnesses such as heart failure is performed by family caregivers. Farran9 estimates that 90% of care of patients with chronic illness care in the United States is delivered by family caregivers. Indeed, supporting family caregivers in order to provide ongoing quality care for chronically ill individuals is a national health priority.10 In the landmark Caregiver Health Effects Study,11 after 4 years, with controls for demographic and common clinical diseases, 392 elderly caregivers (66–96 years old) of patients with disability had a significantly higher mortality rate than did the 427 noncaregivers. Furthermore, caregivers who reported having emotional strain as a result of caregiving were 63% more likely to die compared with the noncaregivers.11 In other studies, 11–14 caregivers of chronically ill patients have reported stress, burden, depression, anxiety, and poor physical and emotional health. Caregivers of patients with heart failure have reported problems similar to those of caregivers of patients with other chronic illnesses, although some differences within the context of heart failure may present unique challenges.15 For example, the frequent periods of exacerbation leading to hospitalizations may contribute to caregivers’ stressors among those who care for patients with heart failure. The need to monitor signs and symptoms to prevent decompensation may be a challenge to caregivers of heart failure patients that does not occur with other disorders. The cognitive impairments that occur in 25% to 50% of patients with heart failure may also increase caregivers’ stress.16 Recent advances in medical therapies, such as the implantation of defibrillators and ventricular assist devices, may further contribute to caregivers’ stressors and burden because of increased needs for care of these devices and increased health care visits. Overall, caregivers of patients with heart failure report high stress, burden (defined as the overall demands of caregiving), depressive symptoms, and poor emotional and physical health.15, 17–21 Guided by the theoretical and empirical literature on family caregiving stress, burden, and other outcomes11,15,17–25 we conducted this study to investigate predictors of family caregiving outcomes in heart failure. Our primary purpose was to determine predictors of family caregiving outcomes among caregivers of patients with heart failure. We hypothesized that caregivers’ medical health condition, age, family functioning, perceived control, depressive symptoms, anxiety, and perceived caregiving stress at baseline would be predictive of self-reported caregiving outcomes and physical and emotional HRQL at 4 and 8 months after collection of baseline data. Our secondary purposes were to identify the tasks caregivers report as most difficult and most negative self-reported caregiving outcomes.

We studied the in vivo interaction of ceftazidime and tobramycin in normal volunteers and anuric patients given each drug separately or both drugs in combination. Kinetic analysis of plasma concentration data showed minor changes in the disposition of these agents when they were given concurrently. However, the resulting clearance of both tobramycin and ceftazidime was unchanged when these drugs were given concurrently. The volume of distribution of tobramycin at steady state was increased by 20% in normal volunteers when given with ceftazidime. The increase in distribution was accompanied by a slight decrease in ceftazidime elimination rate. No additional alteration in dosing over those necessary to adjust for a decrease in renal function is necessary when giving this combination.

To test the hypothesis that renal failure alters the disposition of cibenzoline in humans, an absolute bioavailability and elimination kinetic study was performed. We used the simultaneous administration of a stable isotope variant (SASIV). Eight healthy volunteers and eight matched hemodialysis patients each received simultaneously an 80-mg intravenous infusion of 15N-2-cibenzoline and a single 80-mg cibenzoline capsule. Cibenzoline plasma concentrations were assayed by a gas chromatographic-mass spectrometric assay. A compartment-independent kinetic analysis showed a plasma clearance of 707 mL/min and an elimination half-life of 7.3 hours after the intravenous dose in healthy volunteers. In renal-failure patients, cibenzoline clearance decreased to 224 mL/min and half-life increased to 22.4 hours. Decreased plasma clearance was due to decreases in both renal and nonrenal clearance. Absolute bioavailability was 83% and 90% in healthy volunteers and renal-failure patients, respectively. Hemodialysis accounted for only 13% of drug clearance.

The effect of drug dose on piperacillin elimination kinetics was examined in 27 adult subjects with varying renal function. Piperacillin, 15 mg/kg or 60 mg/kg, was given by bolus intravenous injection. The elimination half-life (t1/2) increased five-fold and plasma clearance (Clp) decreased by 80% in patients with renal failure. Both parameters were dose dependent in patients with normal renal function, but not in patients with renal insufficiency. Piperacillin dose dependent elimination is due primarily to capacity limited renal excretion.

Mezlocillin kinetics was examined in 28 adult subjects with varying renal function. Mezlocillin, 3 gm, was infused over 30 min. Mean peak plasma concentrations ranged from 204 to 253 mg/l. When the area under the curve (AUC) was plotted against creatinine clearance (CCr), the relationship found was expressed by the equation . From this relationship a dosage nomogram was derived describing a power function with the following equation: Dose fraction . Therapeutic guidelines are suggested. Clinical Pharmacology and Therapeutics (1980) 28, 523–528; doi:10.1038/clpt.1980.197

To test the hypothesis that renal insufficiency alters nizatidine disposition, we determined the pharmacokinetics of nizatidine and its major metabolite after a single oral dose in normal volunteers and patients with various degrees of renal dysfunction, after a single intravenous dose in normal volunteers and patients with severe renal failure and during hemodialysis. After intravenous administration the elimination half-life increased from 1.5 +/- 0.2 hours in normal volunteers to 6.9 +/- 3.3 hours in patients with renal failure. The plasma clearance decreased from 0.59 +/- 0.07 L/kg/hr in normal volunteers to 0.14 +/- 0.02 L/kg/hr in patients with renal failure. Nizatidine bioavailability was nearly 100% in normal volunteers but decreased to 75% in patients with renal failure. The volume of distribution was 1.3 +/- 0.1 L/kg in normal volunteers and was not different in patients with renal failure. Nizatidine protein binding was about 30% in normal and uremic plasma. The drug was not substantially removed by hemodialysis. Patients with creatinine clearances less than 50 ml/min/1.73 m2 should receive 150 mg nizatidine once each evening. Patients with creatinine clearances less than 20 ml/min/1.73 m2 should receive 150 mg nizatidine every other night.

To establish elimination kinetics of mezlocillin in patients with hepatic insufficiency, we gave eight normal subjects and four patients with hepatic insufficiency and normal renal function a single 3-gm dose of mezlocillin by intravenous infusion. Subjects with hepatic insufficiency all had serum bilirubins levels of above 3 mg/dl, Prothrombin times more than 2 sec longer than control, and Creatinine clearances above 60 ml/min. Mezlocillin concentrations were determined by microbiologie assay. Kinetic analysis was by model-independent methods. Elimination half-life was 0.96 hr for subjects with normal liver function and 2.62 hr for patients with hepatic insufficiency. Mean total body clearance for normal subjects was 247 ml/min, while in patients with hepatic insufficiency it was 125.4 ml/min. We conclude that hepatic insufficiency prolongs mezlocillin elimination and suggest that therapeutic guidelines be set up. Clinical Pharmacology and Therapeutics (1983) 33, 73–76; doi:10.1038/clpt.1983.10

We evaluated the utility of chloride titrator sticks for facilitating the assessment of dietary salt intake, in a systematic series of clinical trials. These inexpensive devices were applied daily to 24-h or nocturnal urine specimens, thereby avoiding the inter- and intra-subject variability in salt excretion which confounds the use of occasional 24-h urine collections. Chloride and sodium concentrations in urine were highly correlated (r greater than 0.92) in either nocturnal, diurnal, or 24-h collections. The quantitative chloride titrator estimates and measured chloride concentrations were highly correlated as well (r greater than 0.99). The qualitative chloride titrator was graded on a simple scale, and was successfully employed by outpatients attempting to limit their salt intake. Commonly used antihypertensive medications did not interfere with the determinations. Additional chloride intake, such as supplemental potassium chloride, interfered with estimates of salt ingestion, but if the daily amount of potassium chloride supplement was constant, adjustments in interpretation could be made. Renal insufficiency introduced a systematic over-estimation of salt intake by the qualitative chloride tirator, but only at high salt intakes. Relative estimates of salt intake in subjects with renal failure were still possible. We conclude that chloride titrators can facilitate the management of patients who require a prescribed salt intake.

To determine multiple-dose kinetics of the quinoline carboxylic acid derivative ciprofloxacin, we gave 12 normal subjects ciprofloxacin, 250 mg by mouth every 12 hr for 13 doses. Plasma concentrations were measured by HPLC after the first, seventh, and thirteenth doses. Peak and trough plasma concentrations were measured daily. Ciprofloxacin was rapidly absorbed from the gastrointestinal tract and reached maximum serum concentrations about 1 hr after dosing. Ciprofloxacin elimination t1/2 increased from 3.71 hr after the first dose to 6.51 hr after the thirteenth dose (P less than 0.05). Apparent plasma clearance decreased from 0.823 to 0.629 l/kg/hr because of decreased nonrenal clearance. Drug cumulation did not occur throughout the experiment. We conclude that concentrations of ciprofloxacin in excess of the minimum inhibitory concentrations for many important pathogens can be achieved in plasma and that controlled clinical trials of ciprofloxacin efficacy in selected systemic infections are warranted.

To establish therapeutic guidelines for tobramycin use in patients receiving continuous ambulatory peritoneal dialysis (CAPD), we studied tobramycin single-dose kinetics in CAPD patients. Tobramycin was studied after a 1.5-mg/kg dose given either intravenously (TOB-IV) or intraperitoneally (TOB-IP). TOB-IV provided a plasma concentration above 3 mg/l at 12 hr with a t 1/2 of 39.5 hr. When tobramycin was given intraperitoneally, 52% of the dose was absorbed; peak plasma concentrations were only 1.8 mg/l, and the t 1/2 was 35 hr. CAPD accounted for only 15% to 20% of total body clearance in both groups. The kinetic principle of superposition was used to predict plasma concentrations after repeated TOB-IP. A model using once-a-day dosing predicted that a loading dose of 4 mg/kg followed by 1.5 mg/kg would achieve steady-state plasma concentrations of 2.8 to 4.2 mg/l. Another model using tobramycin in each exchange predicted that a loading dose of 3 mg/kg followed by 0.3 mg/kg would provide steady-state plasma concentrations of 2.8 to 3.1 mg/l. These data should be useful in treating CAPD patients with tobramycin who have nonperitoneal gram-negative aerobic bacterial infections, as well as those who require the drug for peritonitis.

To elucidate patterns of dietary sodium ingestion in free-living subjects, we collected 26 consecutive 24-hour urine specimens in 18 subjects who had not received instructions to limit the sodium content of their diets, and who were not aware that sodium intake would be estimated from the collections. Nine subjects with plasma creatinine values less than 2 mg/dL had a mean 24-hour UNaV of 156 mEq/d, with an interindividual variability of SD +/- 38 mEq. Their intraindividual variability was 61 mEq. Nine subjects with creatinine values greater than 2 mg/dL had a mean 24-hour UNaV of 108 mEq/d (P less than 0.05). The intraindividual variability of these subjects was 39 mEq/d. Subjects with normal renal function ingested more sodium than subjects with renal insufficiency, although the variability in both groups was extensive. These data confirm and extend earlier observations and illustrate the difficulty in identifying biologic correlations in the presence of considerable intraindividual variability. They underscore the futility of estimating mean dietary sodium intake with a single or occasional 24-hour urine collection in both normal subjects and patients with renal insufficiency.

To test the hypothesis that the supplementation of dietary calcium intake influences sodium homeostasis, the renin-angiotensin system, and sympathetic nervous system in a manner that might evoke a decrease in arterial blood pressure, we gave 16 participants (eight normal and eight with hypertension) placebo for 8 days, followed by 500 mg elemental calcium as the carbonate salt twice a day for 8 days. The same diet was prepared for each meal for the entire study. Sodium intake was fixed for each participant and averaged 150 mEq/day. All urine was collected every day. Blood was drawn at the end of the placebo and calcium periods for determinations of plasma renin, aldosterone, and norepinephrine values. Calcium supplementation increased urinary calcium excretion significantly in both groups. However, calcium supplementation failed to influence sodium or potassium excretion, serum electrolytes, total serum calcium, renin, aldosterone, or norepinephrine levels, or heart rate. Systolic and diastolic blood pressures were not influenced in normal subjects, but in patients with hypertension the supine systolic blood pressure decreased significantly. We conclude that blood pressure lowering effects of calcium, should they occur, are not likely the result of augmented urinary sodium excretion or of straight-forward influences on the renin-angiotensin system or sympathetic nervous system. Clinical Pharmacology and Therapeutics (1986) 39, 414–419; doi:10.1038/clpt.1986.64

To test the hypothesis that renal failure alters the absorption and metabolism of nitrendipine and the renal elimination of its metabolites, we gave six normal men and 16 men with various degrees of renal dysfunction a single 20 mg oral dose of nitrendipine. Plasma nitrendipine and nitrendipine pyridine analog metabolite concentrations were measured by HPLC 14 times during 48 hours after dosing. The urinary excretion of four additional metabolites was measured. Standing and supine arterial blood pressure was measured 14 times during the 48 hours after dosing. The mean nitrendipine t1/2 was 2.8 +/- 2.1 hours and that of the metabolite was 3.4 +/- 3.9 hours. No significant effect of decreased renal function on any kinetic parameter was demonstrated. Plasma nitrendipine concentrations correlated with decreased blood pressure, but metabolite concentrations did not. We conclude that renal insufficiency does not alter nitrendipine kinetics in man.

The pharmacokinetics of netilmicin were examined in 25 adult subjects, 7 normal subjects, and 18 patients with renal impairment. Five were dialysis patients who were studied on and off dialysis. Netilmicin, 2 mg/kg, was infused intravenously over 1 h. The peak serum concentration ranged from 9 to 11 μg/ml. The mean biological half-life of netilmicin for subjects with a creatinine clearance (Ccr) > 70 ml/min was 2.7 h, for those with Ccr > 25 < 70 ml/min it was 10 h, for those with Ccr > 4 < 25 ml/min it was 32 h, and for those who were anephric it was 42 h. Ccr was correlated positively with the elimination constant and the drug's serum clearance. It was negatively correlated with the drug's volume of distribution. The dialyzer clearance of netilmicin was positively correlated with plasma flow rate and was similar to values previously reported for gentamicin. Netilmicin behaves in a fashion similar to other aminoglycosides. Therapeutic guidelines are suggested.

Moxalactam is the first representative of a new class of potent beta-lactam antibiotics. To establish dosage recommendations, the kinetics of moxalactam elimination were studied in 20 patients with various degrees of renal dysfunction. After a 1-g intravenous bolus injection, the elimination half-life increased from 2.2 +/- 0.1 hr in normal subjects to 22.3 +/- 1.7 hr in anuric patients. Similar correlations were shown between the rate of creatinine clearance and the rate of plasma clearance, the rate of renal clearance, and the overall elimination rate constant of moxalactam. No changes in the distribution volumes or metabolic clearance rates of moxalactam were detected. A nomogram for adjustment of moxalactam dosage in patients with any level of renal function was generated, and specific recommendations for moxalactam dosage are discussed.

To establish therapeutic guidelines for vancomycin usage in patients receiving continuous ambulatory peritoneal dialysis (CAPD), we studied single-dose kinetics of vancomycin in CAPD patients. Vancomycin was studied after a 10-mg/kg dose was given intravenously (VAN-IV) or intraperitoneally (VAN-IP). VAN-IV provided a plasma concentration above 10 mg/l at 12 hr, with a t 1/2 of 81 hr. When VAN-IP was given, 65% was absorbed; peak plasma concentrations were only 6.3 mg/l, and t 1/2 was 66 hr. CAPD accounted for only 15% to 17% of total body clearance in both groups. The kinetic principle of superposition was used to predict plasma concentrations after repeated VAN-IP doses. A model with once-a-day dosing predicted that a loading dose of 30 mg/kg followed by 7 mg/kg would achieve steady-state plasma concentrations of 11 to 14.8 mg/l. Another model with vancomycin in each exchange predicted that a loading dose of 30 mg/kg followed by 1.5 mg/kg would provide plasma concentrations in excess of 10 mg/l at 180 hr. These data should be useful in vancomycin treatment of CAPD patients who have nonperitoneal gram-positive bacterial infections, as well as those who have peritonitis.