Pharmacokinetics of vancomycin in patients undergoing continuous ambulatory peritoneal dialysis

Expressions are presented to describe the absorption and also clearance of drugs administered into the peritoneal cavity of patients undergoing continuous ambulatory peritoneal dialysis (CAPD). Application of the expressions to vancomycin kinetics in five male CAPD patients showed that therapeutic levels of vancomycin can readily be achieved and maintained in the systemic circulation by administering the appropriate loading and maintenance doses. The intrinsic peritoneal clearance of vancomycin reported here is higher than the apparent clearances reported previously, averaging 300 to 500 ml/min under the conditions used in this study. The low apparent clearances previously reported are useful clinically although they do not represent the true efficiency of vancomycin removal by CAPD. The degree to which apparent clearance underestimates the true intrinsic clearance is exponentially related to the dwell time of dialysate in the peritoneum. Intraperitoneal administration is a practical alternative to other routes for CAPD patients needing antibiotic or other therapy.

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confidence: 57%

Vancomycin disposition during continuous ambulatory peritoneal dialysis: a pharmacokinetic analysis of peritoneal drug transport

Rogge¹,

Johnson²,

Zimmerman³

et al. 1985

“…administration of vancomycin, a slow distribution phase was apparent. This delayed period of distribution was previously described in patients with normal renal function (3,6,9); however, it seems that patients with end-stage renal disease have an even more prolonged distribution phase (2,4,5,11 …”

Section: Discussionmentioning

confidence: 80%

“…Studies on intraperitoneal (i.p.) administration have revealed 50% absorption of drug with low concentrations in serum and subtherapeutic dialysate concentrations over a 72-h period (2,16). Consequently, on the basis of these data we designed the present study to (i) compare vancomycin pharmacokinetics after a 30-mg/kg (body weight) i.…”

mentioning

confidence: 99%

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Comparative study of intraperitoneal and intravenous vancomycin pharmacokinetics during continuous ambulatory peritoneal dialysis

Morse¹,

Farolino²,

Apicella³

et al. 1987

The pharmacokinetic characteristics of vancomycin were investigated in eight patients undergoing continuous ambulatory peritoneal dialysis. A crossover design was used. Four noninfected patients received both a 15-mg/kg (body weight) intravenous dose and a 30-mg/kg intraperitoneal (i.p.) dose. Bioavailability ranged from 0.35 to 0.65 after i.p. administration. i.p. absorption was rapid, with concenttrations in serum of 8.8 ± 6 ,ug/ml noted at-1 h and peak values of 30.4 ± 7 ,ug/ml at 6 h. A slow distribution phase was apparent, with a terminal eliminatioli phase emnerging after 12 to 24 h. Vancomycin was eliminated slowly, with a mean total clearance of 5.0 ± 1.3 ml/min, and concentrations in serum were 7.0 ± 1.2 ,ug/ml at 168 h. The mean serum half-life was 91.7 ± 28.1 h, and similar pharmacokinetics were noted after intravenous administration. Subsequently, four patients with catheter-related exit site or tunnel infections received a 30-mng/kg i.p. dose of vancomycin and displayed a similar kinetic pattern. This method of administering vancomycin achieved therapeutic serum and end-dwell dialysate concentrations over a 1-week period, represents a simple, cost-effective therapy which avoids the possibility of infusion-related toxicity, and deserves further investigation in patients with continuous ambulatory peritoneal dialysis-related peritonitis.

“…Patients have been evaluated on the basis of normal or abnormal renal function (13,20,23,28). Numerous studies characterizing vancomycin disposition in both hemodialysis and peritoneal dialysis patients have been published (2,17,19,21,33). Patients have also been characterized on the basis of normal or abnormal hepatic function (4).…”

Section: Resultsmentioning

confidence: 99%

Effect of obesity on vancomycin pharmacokinetic parameters as determined by using a Bayesian forecasting technique

Vance‐Bryan

Guay

Gilliland

et al. 1993

100

Few data exist concerning the effect of obesity on the pharmacokinetic parameters of vancomycin. The purpose of this investigation was to assess the effect of obesity on vancomycin pharmacokinetic parameters in 95 nonobese and 135 obese adult patients (age range, 18 to 92 years) receiving vancomycin. All subjects had normal renal function as defined by a creatinine concentration in serum of c1.5 mg/dl (mean estimated creatinine clearance 1 standard deviation, 76 34; range, 23 to 215 ml/min). Vancomycin concentrations in serum were determined by the fluorescence polarization immunoassay. All data for vancomycin concentration in serum versus time for each course of therapy were fitted by using a two-compartment Bayesian forecasting program. Subjects were stratified into nine groups on the basis of the percent difference between actual body weight (ABW) and lean body weight (LBW) (>-10o, -10 to 0%o, >0 to 10%,, > 10 to 20%o, >20 to 30%o, >30 to 40o, >40 to 50%, >50 to 60%, >60%). Analysis of variance with post hoc Scheffe's testing revealed that statistically significant differences occurred in terminal disposition half-life (t1/211) between the extremes of modestly obese (group 4) and morbidly obese (group 9, P < 0.05) patients. Similar analysis with distribution volume (V') identified significant differences in patients at or near their LBW (groups 2 to 4) and patients who were morbidly obese (groups 8 and 9, P < 0.05). Multiple regression models for the pharmacokinetic parameters V, tl/2", and vancomycin total body clearance were developed to assess the joint predictive power of LBW, ABW, and percent over LBW, controlling for the effects of age, initial creatinine concentration in serum, initial creatinine clearance, and gender. In the final model for V, both ABW and percent over LBW were independent and significant predictors. For total body clearance, only ABW was significant and predictive. Percent over LBW was a significant and independent predictor of t,12,. LBW is not predictive of these pharmacokinetic parameters and should not be used for initial dosing. On the basis of these data, ABW appears to be superior to LBW for calculating initial dose requirements for vancomycin.