New York State primary care physicians' attitudes to community pharmacists' clinical services.

BACKGROUND: Recent changes in education law and regulations governing the practice of pharmacy in New York State have extended the clinical responsibilities of pharmacists. There is limited information in the United States about physicians' opinions of these potential activities by pharmacists. OBJECTIVE: To determine the attitudes of New York State primary care physicians, who practice in a community setting, of community pharmacists as providers of these services, as well as further extended services. METHODS: Questionnaires were mailed to a randomly selected sample of 1400 board-certified internists and family practitioners chosen from New York State counties with populations of less than 251,000. Questions were structured to determine perceptions toward specific extended roles, pharmacists' dispensing of particular drugs without a prescription, the current role of pharmacists, and the relationship between the professions. RESULTS: There were 630 (47.4%) responses, of which 594 (44.7%) were analyzed. Most physicians (93%) agreed that pharmacists should report adverse drug reactions and advise them on cost-effective prescribing (75.6%). Few (23%) believed that pharmacists should initiate a community pharmacy and therapeutics committee. Most responders (64%) agreed that pharmacists could provide, without a prescription, a 3-day course of a vaginal cream containing 2% butoconazole for vaginal candidiasis in nonpregnant women and a rectal suppository containing steroids for hemorrhoid sufferers (61%). However, few (5%) agreed with dispensing antibiotics for sore throats or a 4- to 6-week supply of ranitidine for nightly "point" abdominal tenderness that is relieved by food (5%). Most physicians agreed that pharmacists should provide their patients with information concerning the drug's dose and administration (92%), possible adverse drug reactions (89%), and possible food and drug interactions (97%). Few believed that pharmacists should provide screening services for their patients. CONCLUSIONS: This survey suggests that most physicians support the current patient-counseling activities of community pharmacists. However, there was little support for limited prescribing by pharmacists, even within specific protocols. Increased information to patients was deemed desirable, but few physicians believed that pharmacists should provide health screening services.

Pharmacokinetics of intraperitoneal cefazolin and ceftazidime coadministered to CAPD patients.

PURPOSE: Guidelines for empiric treatment of PD-related peritonitis published in 2000 recommend concurrent intraperitoneal (IP) cefazolin and ceftazidime. The pharmacokinetics (PK) of these agents combined have not been studied. This study was designed to determine the PK of combined IP cefazolin and ceftazidime in CAPD patients. DESIGN: Prospective PK study in seven non-infected CAPD patients. PROCEDURES: Patients had a peritoneal equilibration test (PET), then received one IP dose of cefazolin and ceftazidime (15 mg/kg each) co-administered over a 4-hour dwell, then performed three CAPD exchanges over the next 16 hours. Serum and dialysate samples collected over the 20-hour study period were assayed for drug concentrations by HPLC. OUTCOME MEASURES: PK parameters. STATISTICAL METHODS: Correlations were tested between PET and PK parameters using the Pearson-product correlation coefficient. MAIN FINDINGS: Serum cefazolin and ceftazidime levels exceeded the minimum inhibitory concentrations for susceptible organisms (8 mg/L) throughout the 20 hour study period. Mean cefazolin and ceftazidime PK parameters included: bioavailability, 71% and 63%; elimination rate constant, 0.031 and 0.045 h -1 ; total clearance, 5.8 and 16.0 ml/min; peritoneal clearance, 1.6 and 3.9 ml/min; renal clearance, 2.3 and 3.9 ml/min, respectively. Predictive equations suggest that 1000 mg IP of cefazolin and of ceftazidime every 24 hours would produce average steady-state trough serum cefazolin and ceftazidime concentrations of 70 +/- 52 mg/L and 17 +/- 7 mg/L, respectively. There was no correlation between PET and PK parameters. CONCLUSIONS: Co-administration did not adversely affect the PK of either agent. IP cefazolin and ceftazidime (15 mg/kg) produced adequate serum and dialysate concentrations in CAPD patients for 20 hours. PK predictions suggest that most patients would achieve adequate cefazolin and ceftazidime concentrations with 1000 mg IP once-daily. Anuric patients and those with significant residual renal function may require a more individualized approach.

Clearance from dialysate and equilibration of intraperitoneal vancomycin in continuous ambulatory peritoneal dialysis.

This article reports on a study of the disposition of loading doses (1g and 15 mg/kg) of vancomycin given intraperitoneally to 6 patients on continuous ambulatory peritoneal dialysis with Gram-positive peritonitis. Dialysate samples were collected every 30 minutes during the first dwell, and serum samples were collected after the first 5 exchanges and after 7 or 14 days. The dialysate concentration/time data were fitted to a monoexponential curve for 4 patients and to a biexponential curve for 2 others. Dialysis clearance was 0.73 +/- 0.04 L/h (1g dose) and 0.70 +/- 0.23 L/h (15 mg/kg dose). Total body clearance was 0.51 +/- 0.36 L/h. Serum concentrations reached 14 to 18 mg/L (15 mg/kg dose) and 6.75 to 24 mg/L (1g dose) at the end of the first dwell. The half-life of equilibration of vancomycin across the peritoneal membrane was 2.5 +/- 2.3 hours. Intraperitoneal loading doses of vancomycin produce concomitant serum concentrations in excess of the minimum inhibitory concentrations for susceptible organisms. Administration on a milligram per kilogram basis produces more consistent serum concentrations than using a standard loading dose which is not based on bodyweight.

Bioavailability of bumetanide in grossly oedematous patients.

A pharmacokinetic study was undertaken to determine the bioavailability of bumetanide in grossly oedematous patients. Six nephrotic patients were administered bumetanide 2mg orally (as tablets) and intravenously as single doses, in a randomised fashion. Serum bumetanide concentration-time profiles were characterised. Data were fitted to a 2-compartment model (5 patients) and a 3-compartment model (1 patient). Analysis of the areas under the curves showed a bioavailability of 0.84 +/- 0.2, which is similar to that in normal individuals. It is suggested that the bioavailability of oral bumetanide in oedematous patients is not altered significantly and that the apparent resistance to diuretics in such patients may be due to another cause.

Prediction of serum vancomycin concentrations following intraperitoneal loading doses in continuous ambulatory peritoneal dialysis patients with peritonitis.

The pharmacokinetics of vancomycin were studied in continuous ambulatory peritoneal dialysis patients with peritonitis. Six patients received an intraperitoneal loading dose of 15 mg/kg and 4 received an intraperitoneal dose of 25 mg/L. The ability of 2 methods to predict serum concentrations during the loading dose exchange was determined. The mean serum concentration after the exchange was 17.8 +/- 2.2 mg/L in patients receiving the loading dose. The mean dialysis clearance in all patients was 0.94 +/- 0.34 L/h. 66.6 +/- 13.4% of a dose was absorbed into the circulation in 4 h. The volume of distribution was 0.61 +/- 0.46 L/kg, and the half-life for equilibration of vancomycin into the circulation from dialysate was 2.76 +/- 0.94 h. Two methods of predicting serum vancomycin concentrations were tested, with 1 method predicting values significantly different from measured concentrations while the other did not. Serum vancomycin concentrations can be accurately predicted during a loading dose exchange.

Parenteral iron use in the management of anemia in end-stage renal disease patients.

Intravenous iron is required by most dialysis patients receiving erythropoietin (EPO) to maintain an adequate hematocrit. In the United States, there are currently two parenteral iron preparations, iron dextran and iron gluconate, approved for such use, and a third product, iron sucrose, is under development. This article reviews each of these products. Each of the iron products increases the efficacy of EPO use in anemia management. There is considerable experience in the United States and elsewhere with the use of iron dextran. Although it is clinically effective, iron dextran is also associated with significant morbidity from both dose-dependent and -independent side effects. The slow release of iron from this complex necessitates a delay in monitoring iron indices after the administration of large doses of iron dextran. Recommended doses of iron sucrose appear very safe with little risk of anaphylactic reactions. Adverse effects are uncommon and not life threatening. If approved for use in the United States, iron sucrose may be a safe and effective alternative to iron dextran. Iron dissociates from iron gluconate quite rapidly and may increase the production of ionized free iron. Iron gluconate may be a safe alternative to iron dextran for patients with severe reactions, including anaphylaxis. The risk of allergic reactions to iron gluconate is very low. The exact place in therapy for the newer iron complexes remains unclear. Currently available data suggest that iron sucrose and iron gluconate may have diminished adverse effect profiles when compared with iron dextran. Additional clinical experience will establish the role for these new iron products.

Pharmacokinetics of intermittent intraperitoneal ceftazidime.

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.

Erythropoietin and iron use in peritoneal dialysis patients. Report from the 1997 HCFA end-stage renal disease core indicators project.

The HCFA ESRD Core Indicators Project is designed to assess several key indicators of care in peritoneal dialysis patients, including anemia management. Information on hematocrit levels, epoetin alfa dosing, estimates of iron stores, and iron therapy as obtained in a national sample of 1,219 peritoneal dialysis patients are described. The average hematocrit was 32.8% +/- 3.8%, and severe anemia (hematocrit < 25%) occurred in 1.4% of PD patients. The mean weekly epoetin alfa dose was 134.6 U/kg. In general, there was an inverse relationship between hematocrit and epoetin alfa doses. Most (83%) of PD patients received iron therapy, with only 8% of patients receiving intravenous iron. The mean serum ferritin was 303 ng/mL, with 64% of patients having a ferritin greater than 100 ng/mL. The mean transferrin saturation was 28%, with 60% of patients having a value of less than 20%. There was an inverse relationship between serum ferritin levels and hematocrit but no relationship between hematocrit and transferrin. It is concluded that there could be improvement in the epoetin alfa and iron management in many patients.

Cefazolin dialytic clearance by high-efficiency and high-flux hemodialyzers.

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.

Absorption interactions with fluoroquinolones. 1995 update.

The utility of the fluoroquinolone class of antibiotics is rapidly expanding due to their favourable pharmacokinetic profile and the continuing development of new compounds. These agents are often used for indications not successfully treated with other orally available antimicrobials in the past, or for 'step-down' therapy in patients originally treated with intravenous agents. As the usage of these agents expands for serious systemic infections, knowledge of absorptive interactions with fluoroquinolones becomes paramount. Fluoroquinolones are often utilised in dosages and against modestly susceptible pathogens which allow a narrow margin for acceptable decreases in bioavailability. Chelation interactions with multivalent cations can result in inactivation of the fluoroquinolone with ramifications in vitro and in vivo. Chelation interactions have been reported to occur in between 22 and 76% of patients prescribed fluoroquinolones. Concurrent administration of magnesium-aluminum antacids and sucralfate has the greatest effect on the bioavailability of quinolones followed by iron, calcium and zinc. Spacing doses of fluoroquinolones and interactants has been suggested as a method of ensuring adequate quinolone absorption, but this can make optimal administration of the cation interactant difficult, if not impossible.

Bilateral renal cortical necrosis associated with cefuroxime axetil.

Cefuroxime axetil has been associated with few reported adverse effects. We report a case of bilateral renal cortical necrosis in a female after receiving 7 doses over 4 treatment days. The patient presented with worsening symptoms consisting of arthralgias, pruritus, and abdominal pain. Laboratory data obtained was indicative of worsening renal failure and thrombocytopenia. The patient required hemodialysis by the third day. Kidney biopsy revealed cortical necrosis. The possible pathogenesis of cefuroxime axetil causing cortical necrosis in this case and a review of other reported cases of chemical induced renal cortical necrosis is discussed.

Successful management of steroid-resistant nephrotic syndrome using ibuprofen.

We report the first case of the use of ibuprofen for the management of steroid-resistant nephrotic syndrome. A 41 year-old man with nephrotic syndrome, secondary to focal segmental glomerulosclerosis, had persistent nephrotic range proteinuria despite aggressive treatment with steroids and cyclophosphamide. His steroid-resistant nephrotic syndrome resolved rapidly when he was serendipituously started on ibuprofen for the treatment of pericarditis. His proteinuria remained low at about 0.5 g/day over the next two years of treatment with ibuprofen and without any increase in his serum creatinine. He did not receive any ACE inhibitor or calcium channel blocker. An attempt to discontinue ibuprofen resulted in the relapse of his nephrotic syndrome. Upon restarting ibuprofen, his proteinuria decreased to less than 0.5 g/day again. We conclude that ibuprofen has been effective and safe for the management of nephrotic syndrome in this patient. However, careful monitoring is prudent to assess the potential adverse effects of ibuprofen on renal function with prolonged use.

Evaluation of drug-related problems in an outpatient hemodialysis unit and the impact of a clinical pharmacist.

PURPOSE: Drug-related morbidity and mortality are significant problems in the U.S. Recognition and resolution of drug-related problems (DRP) will decrease drug-related morbidity and mortality and promote optimal therapeutic outcomes. It was the objective of this study to identify DRP in hemodialysis outpatients by performing medication reviews; make appropriate recommendations and determine the significance of any interventions; and estimate outcome in terms of any changes in number of medications/patient or doses/day. METHODS: A thorough medication review was conducted with each patient after review of the computerized medication profiles and medical records. Each updated profile was assessed by a clinical pharmacist for the presence of any of the 8 classical DRP plus 2 additional categories (therapeutic duplication and other [specific for dialysis e.g., dry weight]). Appropriate recommendations were made to the physician. Accepted recommendations were deemed as interventions and assigned a significance rank on a published scale of 1 (adverse significance) to 6 (extremely significant) by each of the investigators. A final rank was assigned upon agreement between investigators. Changes in numbers of doses/day or medications/patient were determined. RESULTS: 49 patients were reviewed and 45 patients (21 women, 24 men) were included in the final analysis. Over one month 126 DRP were identified and 102 interventions were made. Drug interactions constituted the most common DRP (27.5%). The second most common DRP (26.5%) was in the dialysis-specific group. The number of interventions per significance rank were as follows: rank 1:0 (0%); rank 2: 7 (6.9%); rank 4: 80 (78%); rank 5: 5 (4.9%); rank 6: 1 (1%). Patients were taking a mean of 10.9 +/- 3.9 medications and a mean of 14.5 +/- 6 doses/day (range, 2-33) prior to the study and 10.7 +/- r and 14.4 +/- 5.8 by the end of the study period. CONCLUSIONS: With the addition of a clinical pharmacist in an hemodialysis unit numerous DRP were detected and interventions made. The majority of interventions were significant and possibly led to better therapeutic outcomes.

Knowledge of hemodialysis and CAPD patients about their prescribed medicines.

A questionnaire was designed to determine and compare the extent of knowledge of 40 continuous ambulatory peritoneal dialysis (CAPD) and 40 hemodialysis (HD) patients about their medicines. It was administered orally to outpatients attending a clinic by an investigator unknown to the patients. Data were collected pertaining to the following target drugs: calcium supplements, phosphate binders, vitamins B and C and folic acid. HD and CAPD groups were closely matched for age and sex. Sixty percent of CAPD and 49% of HD patients were taking four or more medications. The dose of folic acid was accurately recalled by 91% and 71% of CAPD and HD patients. Indications for calcium supplements and phosphate binders were known by only 8% and 30% of CAPD patients compared to 72% and 73% of HD patients. More HD patients knew the indications for all target drugs (p less than 0.01). More CAPD than HD patients knew the expected duration of therapy (p less than 0.01). There was a trend between decreased knowledge of whether the medication was working with increasing age of CAPD patients. Most drug information was supplied by physicians, but many CAPD patients (21%) obtained information from lay sources. When given the opportunity to ask questions about their medicines, only 56% CAPD and 46% HD patients did so. The knowledge of CAPD and HD patients studied was grossly deficient in terms of indications, effectiveness, duration and action to be taken if doses were missed.

Incidence of CAPD peritonitis in patients using UVXD or O-set systems.

Eighty-one patients were placed either on the O-set (39) or the UVXD germicidal system (42). Total experience was 13.7 +/- 8.0 and 17.8 +/- 14.8 months, respectively. There were 48 and 85 new episodes of peritonitis in 24 and 28 patients, respectively, and an additional 11 and 28 episodes of relapse or probable relapse. The peritonitis rate was 1 episode each 11.14 and 8.83 patient months, which was not significantly different. There was no significant difference between the 2 groups in terms of the mean numbers of peritonitis-free days (393.7 versus 503.8) or in the mean time to the first episode of peritonitis (6.60 versus 6.54 months). The odds ratio of relative risk of peritonitis with the two systems was 1:1.17 (O-set:UVXD). There appears to be no difference in ability of the two systems to prevent peritonitis.

Pharmacokinetics of ciprofloxacin in subjects with varying degrees of renal function and undergoing hemodialysis or CAPD.

The pharmacokinetics of a single, oral dose of 750 mg of ciprofloxacin were studied in 35 subjects with various degrees of renal function (Group 1, Clcr > or = 80 ml/min; Group II, Clcr 50-79 ml/min; Group III, Clcr 10-49 ml/min) and on hemodialysis (HD) or continuous ambulatory peritoneal dialysis (CAPD). Blood, urine and CAPD dialysate samples were collected over a period of 48 hours after dosing. Data were fitted using non-linear, least squares regression. The mean Cmax was 3.4 +/- 1.0 mg/l and tmax was 2.3 +/- 0.9 hours. The mean AUC in Group I was 14.7 mg.h/l, Group II was 33.7 (p < 0.001), Group III 63.8 (p < 0.001), HD 57.9 (p < 0.0001) and CAPD 44.3 (p < 0.001). Half-life in Group I was 4.6 h, and was shorter than Group III (11.1 h, p < 0.001), HD (13.4 h, p < 0.001) and CAPD (8.9 h, p < 0.001). Total body clearance and renal clearance demonstrated significant differences also. The dialysis clearance in CAPD patients was 0.53 +/- 0.39 l/h. Peritoneal effluent concentrations varied from 0.6 mg/l during the first exchange, to a peak of 2.2 mg/l during the second, to 0.13 mg/l in the 48 hour (9th) exchange. Dosage adjustments of ciprofloxacin in the presence of renal insufficiency are indicated for subjects with a Clcr < 20 ml/min/1.73m2.

Stability of drug additives to peritoneal dialysate.

OBJECTIVE: The primary literature was reviewed to determine the stability of drug additives in peritoneal dialysis solutions. DATA SOURCES: A MEDLINE search and retrieval, covering the period 1981 to 1994, was undertaken to identify relevant original literature. Additional references were identified from citations within the original literature. Non-English literature was excluded unless an English abstract was provided. STUDY SELECTION: Forty-nine studies were identified. Of these, 24 were directly related to drug stability, 13 were related to the clinical use of the drug additives but included no stability data, and 12 examined other, nonstability aspects of in vitro activity of antibiotics, additives, or drug adsorption in peritoneal dialysis bags and tubing. DATA EXTRACTION: Data included concentrations of drug additives and dialysate solutions, duration and temperatures of storage conditions, types of assay, and whether they were stability-indicating. RESULTS: Stability was defined as the duration of time that the drug concentration remained at 90% or more of the original concentration. Stability was examined under a large variety of conditions. Thirty-one drugs were identified from 20 manuscripts as single-drug additives. Most beta-lactams were stable for 1-2 weeks in a refrigerator and for several days at room temperature. Aminoglycosides were stable for 1-2 days at room temperature. Glycopeptides were stable for several weeks refrigerated or at room temperature. Prolonged storage at room temperature resulted in instability of cefotaxime, ceftazidime, ceftriaxone, and miconazole. Eleven drugs were identified from seven manuscripts as drug combination studies and showed similar stability as single agents. Dialysate concentration appeared to have minimal effect on stability. CONCLUSIONS: Drug additives in peritoneal dialysate, singly or combined, should be avoided unless data are available to support their stability. Additives should be made as close as possible to the time of the exchange. Alternatively, additives should be stored refrigerated, then warmed prior to use. The practice of preparing numerous bags at one time should be avoided. Finally, stability data do not indicate sterile integrity of the dialysate.

Intermittent intravenous piperacillin pharmacokinetics in automated peritoneal dialysis patients.

BACKGROUND: Use of intermittent antibiotic dosing is increasing in the treatment of peritoneal dialysis (PD)-related peritonitis. We studied the pharmacokinetics of intravenous (i.v.) piperacillin in automated PD patients. PATIENTS AND METHODS: Eight patients (3 males, 5 females) were recruited and received a single i.v. dose of piperacillin (35 mg/kg actual body weight). Blood and dialysate samples were collected at the beginning, middle, and end of dwells 1-3 (on cycler), and end of dwells 4-5 (off cycler) for a 24-hour period. Baseline and 24-hour urine samples (nonanuric patients, n = 7) were collected. Pharmacokinetic parameters were calculated assuming a one-compartment model. Glomerular filtration rate (GFR) and piperacillin clearance (CL) values were normalized to 1.73 m2. RESULTS: The patients were 49.5 +/- 10.1 years of age (mean +/- SD) and had been receiving PD for a median of 3 months (range 2-66 months). Dwell times were 2.25 +/- 0.06 hours on cycler and 7.26 +/- 0.14 hours off cycler. Piperacillin half-life was not statistically different on or off the cycler (on cycler 1.99 +/- 0.39 hr, off cycler 4.39 +/- 5.4 hr; p = 0.12) and remained insignificant, even accounting for an outlier (on cycler 2.01 +/- 0.41 hr, off cycler 2.54 +/- 1.48 hr; p = 0.19). Piperacillin total CL (CL(T)) was 31.29 +/- 6.02 mL/minute. Renal CL (CL(R)) and PD CL (CL(PD)) accounted for 8.8% and 16.8% of CL(T); CL(R) correlated well with GFR (CL(R) = 0.86 GFR + 0.1; p < 0.00003). Mean piperacillin serum and dialysate end-of-dwell concentrations were above minimum inhibitory concentration of susceptible organisms (8 microg/mL) for the three cycler exchanges only. Serum and dialysate concentrations predicted using a one-compartment model suggest that i.v. piperacillin 4000 mg would provide adequate concentrations for susceptible organisms over a 12-hour period. CONCLUSION: The current i.v. piperacillin dosing recommendations of 4000 mg every 12 hours for PD-related peritonitis are appropriate for patients on automated PD. Intermittent intraperitoneal piperacillin is not recommended.

Correlation of intraperitoneal antibiotic pharmacokinetics and peritoneal membrane transport characteristics.

OBJECTIVE: To identify correlations between the pharmacokinetic variables that describe drug disposition in peritoneal dialysis (PD) patients and the measures used to assess dialysis adequacy. DESIGN AND METHODS: This retrospective study re-evaluated data collected during previous pharmacokinetic studies for intraperitoneally administered cefazolin, ceftazidime, and gentamicin in continuous ambulatory peritoneal dialysis (CAPD) patients, and intravenous cefazolin and tobramycin in automated PD patients. Pharmacokinetic variables were compared to creatinine clearance (CCr), Kt/V, and peritoneal equilibration test data using the Pearson product correlation coefficient (r). RESULTS: Prominent correlations were found between renal CCr and renal Kt/V, with renal clearances of CAPD cefazolin and ceftazidime, and automated PD tobramycin and cefazolin (r values ranged from 0.698 to 0.986; p < 0.05). CONCLUSION: These findings support current peritonitis treatment recommendations that patients with residual renal function may require higher doses or more frequent drug administration.

Variability in creatinine clearance (CCR) and KT/V due to different methods of calculating volume and CCR.

OBJECTIVE: This study aimed to compare the correlations between KT/V and creatinine clearance (Ccr) calculated by different methods and to determine and compare the correlations between KT/V and Ccr. DESIGN: Nonrandomized, retrospective analysis of data. SETTING: Continuous ambulatory peritoneal dialysis (CAPD) outpatient clinic in a teaching hospital. PATIENTS: All patients were included for analysis if the data collection was complete for the calculations of KT/V and Ccr using five different methods. INTERVENTIONS: Volume of distribution for urea (V) was estimated by four methods: Watson nomogram, ideal body weight (IBW), actual body weight, and total body surface area. Ccr was determined by five methods: Dialysate Ccr was calculated by creatinine (Cr) uncorrected and corrected for the presence of glucose; urinary Ccr was calculated using urinary Cr alone and the average urinary clearance of urea and Cr; and by the Cockcroft and Gault method. MAIN OUTCOME MEASURES: Correlations between KT/V and Ccr. RESULTS: Sixty-three data sets were collected from 52 CAPD patients. The correlations between weekly KT/V and Ccr normalized to 1.73 m2 body surface area were found to be highly variable from one method to another (r2 = 0.012 -0.494). For obese patients (20% above IBW), KT/V values obtained were more variable using the Watson nomogram compared to the IBW and BSA methods. CONCLUSION: KT/V calculated using the Watson nomogram and the Ccr determined using average of urinary urea and creatinine clearance gave the best correlation (r2 = 0.49).