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The intent of this study was to evaluate the appropriateness of commonly used intravenous (iv) vancomycin dosing schemes in patients on automated peritoneal dialysis (APD) using population pharmacokinetic (PK) modelling and Monte Carlo simulation.Data from a single-dose PK study of 10 non-infected APD patients ≥18 years old were analysed. Patients received iv vancomycin (15 mg/kg) followed by three cycler-assisted APD dwells over 8 h, followed by two 8 h dwells. Serum and dialysate samples were collected over the entire 24 h. A three-compartment model was fitted to the data with BigNPAG. Monte Carlo simulation was used to determine the probability of achieving an AUC/MIC ratio of400 in both the serum and the peritoneal cavity for a variety of iv vancomycin dosing schemes (1-2 g every 24-48 h).In the probability of target attainment (PTA) analyses, only 2 g of iv vancomycin every 24 h conferred90% probability of achieving an AUC/MIC ratio of400 for MIC values2 mg/L in the serum. However, this dosing regimen resulted in average trough concentrations20 mg/L. In the peritoneal cavity, no regimen yielded PTA ≥90% for MIC values ≥0.5 mg/L.Although expert guidelines suggest iv vancomycin may be an acceptable empirical therapy for patients on APD with infection, these analyses indicate that iv vancomycin may not be effective for peritonitis but may be a viable option for non-peritoneal infections with MIC values ≤1 mg/L.

While intraperitoneal (i.p.) ceftazidime is commonly used to treat continuous ambulatory peritoneal dialysis (CAPD)-related infections, the ability of i.p. regimens to achieve critical pharmacodynamic targets in both blood and dialysate has not been reported. To understand the pharmacodynamic profile of ceftazidime during CAPD, data were obtained from a single-dose pharmacokinetic (PK) i.p. ceftazidime study that included 10 CAPD patients who received i.p. ceftazidime at 15 mg/kg of body weight. The probability of target attainment (concentrations maintained above the MIC for >60% of the dosing interval [60% T > MIC]) was determined for six simulated regimens. A 3-compartment model with each dialysis dwell modeled as a separate differential equation was fit to ceftazidime concentrations using BigNPAG. Embedded with the final PK model, serum and dialysate concentration-time profiles of ceftazidime at 1, 1.5, and 2 g i.p. every 24 h (q24h) to q48h were simulated using ADAPT 5. The mean population pharmacokinetic parameters were as follows: apparent volume of the central compartment ( V c ), 7.57 liter; apparent volume of the peritoneal cavity ( V pd), 2.44 liter; clearance from the central compartment (CL), 0.379 liter/h; intercompartmental transfer rate constants (first order) between the central and peripheral compartments ( k 12 and k 21 ), 4.66 and 4.88 h −1 , respectively; and intercompartmental transfer rate constants (first order) between the central and peritoneal compartments ( k 13 and k 31 ), 0.111 and 0.227 h −1 , respectively. In serum, the probability of target attainment for MICs of ≤8 mg/liter exceeded 90% for 1.5 to 2 g i.p. q24h to q48h. However, no tested regimen provided adequate dialysate exposure at MICs of ≥8 mg/liter on day 1 without the use of a 3-g loading dose ( post hoc analysis). On day 2, 1.5 to 2 g i.p. q24h or 2 g i.p. q48h provided adequate exposure in the peritoneal cavity. These results should be validated in the presence of infection. Ceftazidime i.p. at 1.5 or 2 g q24h to q48h is recommended for nonperitoneal infections. For peritonitis, a 3-g load with maintenance dosing of 1 to 2 g i.p. q24h or 2 g i.p. q48h is recommended.

While the pharmacokinetic (PK) properties of daptomycin in hemodialysis (HD) patients have been evaluated previously by three groups, resultant dosing recommendations have varied. To address this clinical conundrum, this study combined concentration-time data from these PK evaluations and derived uniform dosing recommendations among patients on HD receiving daptomycin. A two-compartment model with separate HD and non-HD clearance terms was fit to the PK data from these studies by using BigNPAG. Embedded with PK parameters from the population PK analysis, 5,000-subject Monte Carlo simulations (MCS) were performed to identify HD dosing schemes that provided efficacy (cumulative and daily area under the concentration-time curve [AUC] values) and toxicity (trough concentrations of ≥24.3 mg/liter) profiles comparable to those from simulations employing the daptomycin PK model derived from the Staphylococcus aureus bacteremia–infective endocarditis (SAB-IE) study. Separate HD dosing schemes were sought for the two weekly interdialytic periods (48 and 72 h). For the 48-h interdialytic period, intra- and post-HD dosing provided the most isometric cumulative and daily AUCs. For the 72-h interdialytic period, all HD dosing schemes provided noncumulative AUC values from 48 to 72 h (AUC 48–72 ) that were 48–72 values. Increasing the parent dose by 50% intra- or post-HD provided comparable AUC 48–72 values, while maintaining acceptable trough concentration ( C min ) values. When efficacy and toxicity profiles were evaluated for each individual study, higher probabilities for C min reaching ≥24.3 mg/liter were observed in one of the three studies. Given the high probability of C min being ≥24.3 mg/liter in one of the three studies, more intensive creatine phosphokinase (CPK) monitoring may be warranted in HD patients receiving daptomycin.

Scant data exist for the pharmacokinetics (PK) of ertapenem in patients on continuous ambulatory peritoneal dialysis (CAPD). The goals of this study were to characterize the PK profile of ertapenem during CAPD, determine the extent of ertapenem penetration into the peritoneal cavity, and quantify the probability of the target attainment (PTA) profile in the serum and peritoneal cavity. A single-dose PK study was conducted in seven patients on CAPD. Population PK modeling and Monte Carlo simulation determined the probability that ertapenem at 500 mg intravenously (i.v.) every 24 h (q24h) would achieve concentrations in excess of the MIC for 40% of the dosing interval (40% T >MIC, where T is time) in the serum and peritoneal cavity. Monte Carlo simulation was also used to calculate the peritoneal cavity/serum mean and median penetration ratios by estimating the area under the concentration-time curve in the peritoneal cavity and serum (AUC Peritoneal and AUC Serum , respectively) from zero to infinity after a single simulated dose. The population mean (± standard deviation [SD]) values for the apparent volume in the central compartment, clearance, and apparent volume in the peritoneal cavity were 2.78 (0.62) liters, 0.24 (0.07) liters/hr, and 5.81 (2.05) liters, respectively. The mean (SD) AUC Peritoneal /AUC Serum ratio was 1.039 (0.861), and the median penetration ratio was 0.801 (interquartile range, 0.486 to 1.317). In both the serum and peritoneal cavity, ertapenem at 500 mg i.v. q24h was very likely (>90%) to achieve the pharmacodynamic target for MICs of ≤2 mg/liter. The simulations suggest that 500 mg of ertapenem i.v. q24h is very likely to achieve the exposure target associated with clinical efficacy in both the serum and peritoneal cavity against the range of MIC values deemed susceptible by the Clinical and Laboratory Standards Institute.

Introduction Nonsteroidal anti-inflammatory drugs (NSAIDs) are frequently associated with community-acquired acute kidney injury (AKI), a strong risk factor for development and progression of chronic kidney disease. Using access to prescription medication profiles, pharmacists can identify patients at high risk for NSAID-induced AKI. The primary objective of this analysis was to evaluate the effectiveness of a community pharmacy–based patient education program on patient knowledge of NSAID-associated renal safety concerns. Methods Patients receiving prescription medications for hypertension or diabetes mellitus were invited to participate in an educational program on the risks of NSAID use. A patient knowledge questionnaire (PKQ) consisting of 5 questions scored from 1 to 5 was completed before and after the intervention. Information was collected on age, race, sex, and frequency of NSAID use. Results A total of 152 participants (60% women) completed both the pre- and post-intervention questionnaire; average age was 54.6 (standard deviation [SD], 17.5). Mean pre-intervention PKQ score was 3.3 (SD, 1.4), and post-intervention score was 4.6 (SD, 0.9) (P = .002). Participants rated program usefulness (1 = not useful to 5 = extremely useful) as 4.2 (SD, 1.0). In addition, 48% reported current NSAID use and 67% reported that the program encouraged them to limit their use. Conclusion NSAID use was common among patients at high risk for AKI. A brief educational intervention in a community pharmacy improved patient knowledge on NSAID-associated risks. Pharmacists practicing in the community can partner with primary care providers in the medical home model to educate patients at risk for AKI.

Cefazolin dialytic clearance has not been determined in patients undergoing hemodialysis with high-efficiency or high-flux dialyzers. The objective of this study is to determine the pharmacokinetics and dialytic clearance of cefazolin and develop dosing strategies in these patients. Twenty-five uninfected subjects undergoing chronic thrice-weekly hemodialysis were administered a single dose of intravenous cefazolin (15 mg/kg) after their standard hemodialysis session. Fifteen subjects underwent hemodialysis with high-efficiency hemodialyzers, and 10 subjects underwent hemodialysis with high-flux hemodialyzers. Blood and urine samples were collected serially over the interdialytic period, during the next intradialytic period, and immediately after the next hemodialysis session. Serum and urine concentrations of cefazolin were determined by high-performance liquid chromatography. Differential equations describing a two-compartment model were fit to the cefazolin serum concentration-time data over the study period, and pharmacokinetic parameters were determined. Mean dialytic clearance values for cefazolin were significantly greater in the high-flux group compared with the high-efficiency group (30.9 +/- 6.52 versus 18.0 +/- 6.26 mL/min, respectively; P: < 0.05). Cefazolin reduction ratios were significantly greater (0.62 +/- 0.08 versus 0.50 +/- 0.07; P: < 0.005) in the high-flux group compared with the high-efficiency group and correlated well with equilibrated urea reduction. The pharmacokinetic model developed from patient data was used to simulate cefazolin serum concentration data for high-efficiency and high-flux dialyzers. Cefazolin doses of 15 or 20 mg/kg after each hemodialysis session maintained adequate serum concentrations throughout a 2- or 3-day interdialytic period regardless of hemodialyzer type.

Ceftazidime is currently recommended as an alternative first-line agent in the treatment of peritonitis and for Pseudomonas peritonitis. The pharmacokinetics of intermittent intraperitoneal (i.p.) ceftazidime have been poorly characterized. This study was designed to characterize the pharmacokinetic disposition of a single dose of ceftazidime in anuric and non-anuric CAPD patients, over 48 hours. This was a prospective, open label, pharmacokinetic study. The study was conducted in an independent, outpatient dialysis center. Ten volunteer continuous ambulatory peritoneal dialysis (CAPD) patients with and without residual renal function, no peritonitis or antibiotics in the previous 4 weeks, and on CAPD for at least 2 months were recruited. Patients received a single dose of i.p. ceftazidime (15 mg/kg) in the first daytime exchange over a 6-hour dwell, after an overnight dwell. Serum, urine, and dialysate were collected over a 48-hour period. A high-pressure liquid chromatography (HPLC) assay was used to analyze ceftazidime in these samples. Pharmacokinetic parameters were calculated. Six of the 10 patients were non-anuric with a mean residual renal creatinine clearance of 2.9 +/- 1.6 mL/min. The mean +/- SD bioavailability was 72% +/- 14%, and the volume of distribution was 0.34 +/- 0.08 L/kg. The mean serum elimination half-life of 22 +/- 5 hours. The peritoneal clearance was 5.74 +/- 1.6 mL/min. No difference was detected between anuric and nonanuric patients. Mean plasma and dialysate concentrations at 24 hours were 24 +/- 6 microg/mL and 18 +/- 7 microg/mL, respectively, and were 12.0 +/- 3.6 microg/mL and 7.4 +/- 3.1 microg/mL at 48 hours, respectively. Once-daily i.p. dosing of ceftazidime achieves serum and dialysate levels greater than the MIC of sensitive organisms over 48 hours.

Medication regimen simplification may improve adherence in end-stage kidney disease. The effect of nocturnal home hemodialysis (NHHD) on medication burden is unknown. A retrospective pilot study of NHHD patients was conducted. Medication information was collected at baseline, NHHD start, and at 3, 6, 12, 18, and 24 months. SF-36 scores were collected at baseline, 6, 12, and 24 months. The number of medications, pill burden, and number of administrations per day were determined. Medication Regimen Complexity Index was used at each time point as a comparator. Medications for anemia, mineral and bone disorders (MBD), cardiovascular (CV) disease, infection, and vitamins were analyzed for number of medications and pill burden. Thirty-five patients were included. Patients used 10.5 ± 4.4 medications at baseline and 11.8 ± 4.7 at the end of the study (P=NS). Regarding the number of medications, anemia medications, anti-infectives, and vitamins increased; MBD and CV medications decreased by the end of the study. Total pill burden did not change over 24 months, nor did anemia pill burden. Mineral bone disorder and CV pill burden decreased, and vitamins and anti-infective pill burden increased. Daily medication administration times decreased significantly from 5.0 ± 1.5 to 3.6 ± 1.5 by 24 months. Switching to NHHD was associated with a significant increase in Medication Regimen Complexity Index at 24 months (P0.05). SF-36 scores increased significantly once patients began on NHHD. No measure of medication regimen complexity was correlated with the SF-36 score. Medication burden changes over time after starting NHHD. It is unknown what effect NHHD has on adherence or medication costs, and warrants further study in a prospective comparative investigation.

Background: Quantitative ultrasound (QUS) devices provide portable, easy-to-operate, low-cost options for point-of-care screening of bone mineral density (BMD). Community pharmacists should be aware of the precision, sensitivity, and specificity of these devices prior to their purchase. Objective: To determine the precision, sensitivity, and specificity of the Achilles Express ultrasonometer compared with central dual-energy X-ray absorptiometry (cDXA) as well as its utility as a bone density screening device in the community pharmacy setting. Methods: A prospective study in a community pharmacy and outpatient ambulatory clinic was conducted with 2 groups of white women. Group 1 participants were 25–35 years of age (young, healthy), and those in Group 2 were 45 years of age or older (postmenopausal). BMD assessments of the spine and the nondominant wrist and hip were performed using cDXA. Assessments of the heel were performed using the Achilles Express, a QUS device. The main outcome measures were correlation of t-scores between cDXA and QUS measurements using the Pearson correlation test. Results: Twenty-two (30 ± 4 years of age) and 31 (55 ± 17 years of age) women were enrolled into Groups 1 and 2, respectively. Significant correlations between QUS and hip and spine cDXA t-scores were found in both groups. Correlation coefficients for QUS versus hip cDXA were 0.51 (95% CI 0.11 to 0.77) and 0.70 (95% CI 0.46 to 0.85) in Groups 1 and 2, respectively. Correlation coefficients for the QUS versus spine cDXA were 0.64 (95% CI 0.31 to 0.84) and 0.60 (95% CI 0.31 to 0.79) in Groups 1 and 2, respectively. The QUS device has a sensitivity level of 88% and specificity of 71% to detect a hip cDXA t-score of less than –1. Conclusions: The Achilles Express ultrasonometer is a reasonable screening tool to detect low BMD in postmenopausal women.

Background: Patients with chronic kidney disease (CKD) might be at high risk for bone disease. Decreased functional kidney mass contributes to renal osteodystrophy, which might be exacerbated by certain drug therapies. Long-term (≥6 months) corticosteroid treatment is commonly prescribed in patients with glomerular disease, possibly causing bone loss both indirectly and directly, putting the patient at increased risk for fracture. The dual-energy x-ray absorptiometry (DXA) is the current "gold standard" for measuring osteoporosis-related fractures and works by passing ultrasound waves through bone to determine the structural anisotropy in the heel. Objective: This pilot study was designed to determine whether there is a correlation between DXA and quantitative ultrasound (QUS) in detecting corticosteroid-induced osteoporosis. Methods: This open-label pilot study was conducted at the Medical Center Nephrology Clinic, Albany Medical College, Albany, New York. Female patients aged≥18 years with a diagnosis of CKD and/or a history of kidney transplantation and who were receiving long-term corticosteroid treatment were enrolled. Each patient served as her own control and underwent DXA of the hip and spine (DXA-hip and DXA-spine, respectively) and QUS of the dominant and nondominant heels (QUS-dominant and QUS-nondominant, respectively), within 1 week so that conditions were similar in each patient. Results: Eight patients were included in the study (mean [SD] age, 50.2 [11.2] years). A positive correlation was found between DXA-hip and QUS-nondominant ( r 2 =0.76; P=0.009); however, no correlation was found with DXA-spine. Similarly, a positive correlation was found between DXA-hip and QUS-dominant ( r 2 =0.75; P=0.009), but no correlation with DXA-spine was found ( r 2 =0.22). Conclusion: In this small, selected population, QUS showed a fair correlation with DXA-hip but no correlation with DXA-spine. Further studies are needed to determine the effectiveness in other populations.

BACKGROUND: The use of natural products is increasing, but healthcare professionals may underestimate the use of these agents by patients. It is unknown whether natural product use differs between primary care and specialty clinic patients, such as those in a nephrology clinic. OBJECTIVE: To compare patterns of natural product use between primary care and nephrology clinic patients. METHODS: One thousand adult patients from each clinic were randomly mailed an anonymous questionnaire to determine current and past use of natural products. RESULTS: A total of 491 surveys were returned, for an overall response rate of 26% (25% primary care; 28% nephrology clinic). Current use of natural products was similar between the primary care and nephrology groups (34% vs 29%, respectively; p = NS). Primary care patients were more likely to have taken a natural product in the past (57% vs 45%; p < 0.05); Echinacea was the most common product taken by those patients (26%). Green tea was the most common natural product taken by nephrology clinic patients (18%). More primary care patients took Echinacea compared with nephrology clinic patients (26% vs 12%; p < 0.01). Adverse reactions led to discontinuation of the natural product in 7% of respondents. CONCLUSIONS: Active use of natural products was similar between the survey respondents. Documentation and monitoring of natural product use by healthcare professionals working with primary care and nephrology clinic patients are recommended.