B Nataraj1, N V Rao Mamidi, D R Krishna. 1. Drug Metabolism and Pharmacokinetic Laboratory, Dr Reddy's Research Foundation, Ameerpet, Hyderabad, India.
Abstract
OBJECTIVE: The aim of this randomised, double-blind, crossover study was to evaluate the effect of single-dose probenecid on the pharmacokinetics of ofloxacin in eight healthy male volunteers. METHODS: After an overnight fast, and according to a randomised sequence, each volunteer received either single oral ofloxacin 200mg (Hoechst Marion Roussel Ltd., Mumbai, India) or both ofloxacin (1 x 200mg) and probenecid (1 x 500mg) [Geno Pharmaceutical Ltd., Mumbai, India]. Blood samples were collected at regular intervals until 24 hours. Serum concentration versus time profiles for ofloxacin were generated and pharmacokinetic parameters were calculated by noncompartmental model analysis. RESULTS:Elimination half-life, mean residence time and area under the curve were significantly increased (4.86 vs 5.26h; 7.23 vs 7.95h; 10.28 vs 11.9 mg/L . h) [p < 0.01], whereas the total clearance was decreased (19.66 vs 16.95 L/h) [p < 0.01] in the presence of probenecid. Other pharmacokinetic parameters were not significantly affected by coadministration of probenecid. CONCLUSION: Concomitant administration of probenecid with ofloxacin may result in a decreased elimination half-life and consequently increased bioavailability of ofloxacin. Probenecid may be co-prescribed with ofloxacin; patients taking this combination should be closely monitored and dosage reduction should be considered if warranted in high-risk patients.
RCT Entities:
OBJECTIVE: The aim of this randomised, double-blind, crossover study was to evaluate the effect of single-dose probenecid on the pharmacokinetics of ofloxacin in eight healthy male volunteers. METHODS: After an overnight fast, and according to a randomised sequence, each volunteer received either single oral ofloxacin 200mg (Hoechst Marion Roussel Ltd., Mumbai, India) or both ofloxacin (1 x 200mg) and probenecid (1 x 500mg) [Geno Pharmaceutical Ltd., Mumbai, India]. Blood samples were collected at regular intervals until 24 hours. Serum concentration versus time profiles for ofloxacin were generated and pharmacokinetic parameters were calculated by noncompartmental model analysis. RESULTS: Elimination half-life, mean residence time and area under the curve were significantly increased (4.86 vs 5.26h; 7.23 vs 7.95h; 10.28 vs 11.9 mg/L . h) [p < 0.01], whereas the total clearance was decreased (19.66 vs 16.95 L/h) [p < 0.01] in the presence of probenecid. Other pharmacokinetic parameters were not significantly affected by coadministration of probenecid. CONCLUSION: Concomitant administration of probenecid with ofloxacin may result in a decreased elimination half-life and consequently increased bioavailability of ofloxacin. Probenecid may be co-prescribed with ofloxacin; patients taking this combination should be closely monitored and dosage reduction should be considered if warranted in high-risk patients.
Authors: H Lode; G Höffken; P Olschewski; B Sievers; A Kirch; K Borner; P Koeppe Journal: Antimicrob Agents Chemother Date: 1987-09 Impact factor: 5.191