Pharmacokinetics of quinupristin-dalfopristin in continuous ambulatory peritoneal dialysis patients

Quinupristin-dalfopristin may be useful for treatment of organisms causing peritoneal dialysis-related peritonitis, including methicillin-resistant co agulase-negative staphylococci, methicillin-resistant Staphylococcus aureus , and vancomycin-resistant enterococci. The pharmacokinetic profiles of sin gle intravenous doses of this combination streptogramin antibiotic of 7.5 m g/kg of body weight were characterized for eight noninfected patients recei ving continuous ambulatory peritoneal dialysis. Comparison was made to phar macokinetic profiles determined for eight healthy volunteers matched by age , sex and race. Drug was measured in dialysate up to 6 h following the dose . plasma and dialysate were assayed for parent compounds and metabolites. M ean pharmacokinetic parameters were compared between groups. No statistical ly significant differences were observed between groups for maximal concent rations in plasma, times to maximal concentration, areas under the curve, d istribution volumes, rates of total body clearance, or half-lives in plasma for quinupristin and dalfopristin. No statistically significant difference s were observed in maximal concentrations in plasma, times to maximal conce ntration, areas under the curve, or half-lives for cysteine, the glutathion e conjugates of quinupristin, or the pristinamycin IIA metabolite of dalfop ristin. The measurements in dialysate of the parent and most metabolites we re below the expected MICs. Dialysis clearance was insignificant. Quinupris tin-dalfopristin was well tolerated in both groups, causing only mild adver se events that resolved prior to discharge from the study. The disposition of quinupristin, dalfopristin, or their primary metabolites following a sin gle dose was unaltered in patients receiving peritoneal dialysis. Intraveno us dosing of this antibiotic combination is unlikely to be adequate for the treatment of peritonitis associated with peritoneal dialysis.