Moxalactam kinetics during chronic ambulatory peritoneal dialysis

Abstract

Moxalactam kinetics in renal failure were followed in eight patients undergoing chronic ambulatory peritoneal dialysis (CAPD) after a single 1-gm IV infusion. Elimination t 1/2 was 16.7 +/- 2.1 hr, with an apparent volume of distribution of 0.21 +/- 0.01 l/kg and plasma clearance of 10.6 +/- 2 ml/min. In 24 hr, 17.4 +/- 3.1% of the dose was present in the dialysis fluids, and 14.6 +/- 5.7% was excreted in the urine. Renal and peritoneal clearance values were thus 2.3 +/- 1.1 and 2.7 +/- 0.5 ml/min. Peritoneal concentrations were high (22.7 +/- 2.2 micrograms/ml). A recommended dosage schedule is proposed on the basis of moxalactam kinetics during CAPD.

Moxalactam kinetics during continuous ambulatory peritoneal dialysis after intraperitoneal administration

“…Since intravenous administration may be more difficult in such patients, an alternative method of drug administration via the peritoneal route is useful. The pharmacokinetic parameters calculated in this study are in agreement with those reported by Singlas et al (19) after intravenous administration. Similarly, no substantial difference in pharmacokinetics between the intravenous and intraperitoneal route of administration has been observed for cefoperazone (10), cephalexin (4), tobramycin (5), and vancomycin (6).…”

“…The calculated nondialysis clearance for five of these six subjects (excluding patient 8; see below) of 9.7 ± 2.4 ml/min compares favorably with that calculated by Aronoffet al (2) (12.8 ± 2.0 ml/min), Jacobsen et al (9) (9.3 ± 4.9 ml/min), and Singlas et al (19) (4.2 ± 0.6 ml/min) after intravenous administration to subjects with a creatinine clearance of less than 8 ml/min. Jacobsen et al (9) and Aronoff et al (2) determined the concentration of moxalactam in plasma by microbiological assays, using Escherichia coli ATCC 10536 and E. coli ATCC 4157, respectively, as the test organisms.…”

“…Also, in both studies, with similar rates of dialysis fluid exchange, comparable values for dialysis clearance of 2.7 ml/min (Singlas et al [19]), and 2.3 ml/min (present study) were obtained. The percent contribution of CLD was also comparable in both studies, a value of 17.…”

“…After the hemodialysis of patients with renal failure, an adjustment of the subsequent dose is necessary to compensate for the increased clearance of moxalactam during the dialysis period (2, 9, 12). However, for patients with renal failure, who are undergoing CAPD, dosage adjustment to account for any loss of moxalactam via the peritoneal cavity appears unnecessary (19,24). No data are currently available on the pharmacokinetics of moxalactam after singledose intraperitoneal administration.…”

Pharmacokinetics of ornidazole in patients with renal insufficiency; influence of haemodialysis and peritoneal dialysis.

“…A reduction of the volume of distribution in renal failure has already been described for certain drugs; the reasons for such a reduction are not known (Fabre & Balant, 1976;Gibaldi, 1977;Singlas et al, 1983). This reduction of the volume of distribution leads to somewhat higher concentrations than those obtained for the same dose in subjects with normal renal function (Richle et al, 1978).…”