Pharmacokinetics of Quinupristin/ Dalfopristin in Patients with Severe Chronic Renal Insufficiency

Abstract

These results suggest that no formal reduction in the dosage of quinupristin/dalfopristin is necessary in patients with severe chronic renal impairment.

Treatment of Life-Threatening Multiresistant Staphylococcal and Enterococcal Infections in Patients with End-Stage Renal Failure with Quinupristin/Dalfopristin: Preliminary Report

“…The pharmacokinetic behavior of the parent drugs in our study population is in good agreement with previous data in non-hemodialyzed patients with stable preterminal renal impairment [7], although our ESRD patients showed somewhat higher values than the former patients. At the initial phase of treatment pristinamycin II A revealed both lower C max and AUD values in comparison to patients with stable preterminal renal impairment, but the values were comparable at the steady state.…”

“…Adverse reactions were mild and consisted of myalgia without elevation of creatine phosphokinase, headache and dizziness, as already reported with volunteers [7]. Chevalier et al [7] also investigated the pharmacokinetics of Q-D after single administration to 13 patients presenting with stable preterminal renal failure without any signs of infection. Chronic dialysis, hepatic impairment and anemia with hemoglobin < 8 g/dl were considered exclusion criteria.…”

“…These findings might be of clinical relevance for pharmacokinetics of Q-D and its derivatives in patients undergoing hemodialysis. Chevalier et al [7] reported accumulation of quinupristin and its derivatives with corresponding increases of both C max and AUC in preterminal renal failure. The pronounced removal of quinupristin and its cysteine conjugated derivative by dialysis might counteract a further accumulation of these compounds in these patients when multiple doses are administered.…”

“…Both compounds undergo intense metabolism and are primarily eliminated through the bile into the feces [6]. Since data on clinical experience and pharmacokinetics of Q-D and their derivatives are scanty in renal patients and among critically ill patients requiring renal replacement therapy [7], we evaluated clinical efficacy and pharmacokinetics of Q-D in these patients.…”

Infection with Antimicrobial‐resistant Microorganisms in Dialysis Patients

“…The area under the concentration (AUC) curve for quinupristin, dalfopristin, and their metabolites increases about 30–40% in patients with moderate to severe renal failure (Aventis Pharmaceuticals, data on file). Limited data indicate that clearance of quinupristin is not affected in patients with moderate to severe renal failure, but clearance of dalfopristin and some quinupristin metabolites is somewhat reduced (114,115). With a large molecular weight and protein binding of 30% for quinupristin and 60% for dalfopristin, clearance of either parent compound with HD is thought to be negligible (Aventis Pharmaceuticals, data on file).…”