Peritoneal Dialysis International, Vol. 11, pp 59-63,1991 0896-8608/91 $3.00 + .00 Printed in Canada. All rights reserved. Copyright © 1991 Peritoneal Dialysis International Inc. Single-Dose Pefloxacin Pharmacokinetics and Metabolism in Patients Undergoing Continuous Ambulatory Peritoneal Dialysis (CAPD) Paul Nikolaidis1,3, Scott E. Walker2, Nicholas Dombros3, Achilleas Tourkantonis3, Tom W. Paton2, and Dimitrios G. Oreopoulos1 1Department of Medicine, Toronto Western Hospital, University of Toronto, Toronto, Ontario, Canada, 2Department of Pharmacy, Sunnybrook Health Science Centre, University of Toronto, Toronto, Ontario, Canada and 3Department of Medicine, AHEPA General Hospital, University of Thessaloniki, Thessaloniki, Greece Seven adult patients on continuous ambulatory peri toneal dialysis (CAPD) received one dose of pefloxacin, a novel quinolone antibiotic, orally and intravenously on two separate occasions to characterize the pharmacoki netics and metabolism of the drug. Concentrations of both pefloxacin and its active metabolite N-desmethyl pefloxacin (norfloxacin) were measured in serum and dialysate by HPLC. Half-life, total body clearance and peritoneal clearance were determined. The overall elimination half-life was 19.9h. Relative to the IV dose the bioavailability following oral administration of pefloxacin was 76%. The mean serum and dialysate concentrations were similar up to 24 h after the oral or IV dose. After a 6h dwell time the dialysate concentration of pefloxacin was 2.24 mg/L which is above the MICgo for most bacteria responsible for peritonitis in CAPD patients. The peritoneal clearance of pefloxacin averaged 2.5 mL/min. Se rum concentrations of the metabolite norfloxacin were less than 0.5 mg/L during the 24 h study period. We conclude that pefloxacin might be equally effective in the treatment of peritonitis of CAPD after oral or IV administration. Since the peritoneal clearance contributes insignificantly to the elimination of pefloxacin during CAPD, the proposed maintenance regimen of an oral or IV 400 mg dose/day seems to be a reasonable therapy for infections in CAPD patients. KEY WORDS: Quinolones; pefloxacin; norfloxacin; pharmacokinetics; metabolism; peritonitis. Peritonitis caused by Gram-positive and Gram negative microbes despite technological improvements, remains a major problem in CAPD patients. Although the incidence of peritonitis has been decreased to one episode, every 18-24 patient months, difficult infections result in a prolonged hospitalization, catheter loss and temporary or permanent transfer to hemodialysis. This increases the overall cost of Correspondence to: Paul Nikolaidis, Department of Medicine, Toronto Western Hospital, University of Toronto, Toronto, Ontario, Canada. Received March 1, 1990; accepted April18, 1990. treatment and patient morbidity (1). In addition, th - erapeutic failures and relapses often result in the emergence of resistant bacteria to many antibiotics. For these reasons, new antimicrobial agents are always useful in the treatment of CAPD related peri tonitis. Pefloxacin is a new fluorinated quinolone with an extended antimicrobial spectrum against the majority of Gram-negative microbes and staphylococci including methicillin resistant strains (2-4). Furthermore, pefloxac in possesses some favourable phar macokinetic properties which include complete absorption after oral administration, long half-life (1012h) permitting infrequent dosage and rapid pene tration into the intracellular and extracellular space. It is metabolized in the liver to a N- oxide-derivative and to a microbiologically active desmethyl-pefloxacin (Norfloxacin) which are excreted in the urine (5 7). Clinical studies have shown that Pefloxacin is highly effective in a wide range of serious infections (8, 9). The aim of the present study was 1) to determine the kinetic behaviour of pefloxacin after oral and intra venous administration in patients undergoing CAPD; 2) to find out whether the obtained serum and dialy sate levels of the drug are in the therapeutic range for the common causes of peritonitis; and 3) to investi gate the metabolism ofpefloxacin in CAPD patients. METHODS The pharmacokinetics of Pefloxacin were studied in seven patients after giving informed consent approved by the Ethics Committee ofAHEPA University Hospital, Thessaloniki, Greece. All subjects had end stage renal disease with creatinine clearance less than 5 mL/min and had been undergoing CAPD for at least nine months. Patients were excluded if they had any known allergy to quinolo ne antibiotics, if they had peritonitis within two months, or a clinical diagnosis of hepatic disease. Phosphate binders and antacids were discontinued for one day before initiation of the study. Subjects received a single I.V. or oral 400 mg dose of Pefloxacin on two by guest on November 6, 2015 http://www.pdiconnect.com/ Downloaded from