A pharmacokinetic drug interaction study of ceftazidime with clavulanic acid in healthy male Indian subjects

Abstract

Ceftazidime is a third generation cephalosporin with a broad range of activity. Clavulanic acid is a β-lactamase inhibitor. A fixed dose combination, with the wide spectrum of action of ceftazidime and clavulanic acid’s high stability to β-lactamases has been developed by Ranbaxy Laboratories Limited (India). The present study was planned to predict any interaction between ceftazidime and clavulanic acid which could affect the safety and efficacy of the fixed dose combination. The study was an open label, balanced, randomized two-treatment, two-period, two-sequence, crossover, single-dose comparative pharmacokinetic study under fed conditions. A single intravenous injection of the test product containing a fixed dose combination of ceftazidime 2000 mg and potassium clavulanate 200 mg and the reference product containing ceftazidime 2000 mg only, was administered during each period. Serial blood samples were collected until 12 h post-dose in each period. Ceftazidime and clavulanic acid concentration in plasma were determined using two separate LC-MS/MS methods and then pharmacokinetic parameters were evaluated. No significant difference was seen in the mean Tmax, Cmax, AUC0–t, and AUC0–∞ when the drug was administered as ceftazidime alone and in combination with clavulanic acid. The Confidence Intervals for the log transformed parameters Cmax, AUC0–t and AUC0–∞ were within limits of 80–125% of ceftazidime for the test and reference products. The lack of significant difference between the pharmacokinetic parameters for ceftazidime alone and in the presence of clavulanic acid ruled out any significant interaction between ceftazidime and clavulanic acid.