Pharmacokinetics of cefpodoxime proxetil and interactions with an antacid and an H2 receptor antagonist (original) (raw)
1992, Antimicrobial Agents and Chemotherapy
Cefpodoxime proxetil is a new oral esterified cephem antibiotic with a broad antibacterial spectrum. The dissolution of cefpodoxime proxetil is pH dependent. The objectives of this study were to characterize the pharmacokinetics of cefpodoxime proxetil in two diferent oral doses and to examine possible interactions with an antacid, aluminum magnesium hydroxide (Maalox 70), and an H2 receptor antagonist, ftidie. TWo studies involving the same 10 healthy volunteers were performd. In the first study, cefpodoxime proxetil was administered in two doses, 0.1 and 0.2 g. In the second study, two interventions were performed in a randomized crossover design. For one intervention, the volunteers were pretreated with 40 mg of famotidine 1 h before 0.2 g of cefpodoxime proxetil was administered. In the second trial, participants were given 10 ml of Maalox 70 2 h and 10 ml of Maalox 70 15 min before they received 0.2 g of cefpodoxime proxetil. Serum and urine concentrations were determined by high-performance liquid chromatography. For the statistical evaluation, these data were tested by using the pharmacokinetics of 0.2 g of cefpodoxime proxetil from the first study. The maximum concentrations were 1.19 t 0.32 mg/liter after 0.1 g of cefpodoxime proxetil and 2.54 ± 0.64 mg/liter after 0.2 g of cefpodoxime proxetil. The elimination half-lives were 149 min for 0.1 g and 172 mmn for 0.2 g of cefpodoxime proxetil. The total increase in the area under the concentration-the curve (AUC) was dose dependent. Combination with Maalox 70 caused a reduction in the AUC from 14.0 ± 3.9 to 8.44 ± 1.85 mg * h/liter. After famotidine, the AUC decreased to 8.36 ± 2.0 mg . h/liter. Corresponding changes were registered for the maxmum concentration of drug in serum, 24-h urine recovery, and the time to maximum concentration of drug in serum. Cefpodoxime proxetil was well tolerated without any seriously adverse drug reactions.
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