Probenecid affects the pharmacokinetics of ofloxacin in healthy volunteers.
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.


CONCLUSIONS
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.
Nataraj
B
B
Drug Metabolism and Pharmacokinetic Laboratory, Dr Reddy's Research Foundation, Ameerpet, Hyderabad, India.
Rao Mamidi
N V
NV
Krishna
D R
DR