The effects of ranitidine, metoclopromide, and anisotropine methylbromide on the absorption of cefpodoxime proxetil (CS-807) were examined in two studies. Pharmacokinetic parameters of R-3763, an active metabolite of CS-807 by non-specific esterases in the intestinal wall, were calculated and compared.
1) A single dose of ranitidine (150 mg) was administered orally to six healthy male subjects 1. 5 hr before the dose of CS-807 (100 mg). Intragastric pH was monitored through a micro-pH-electrode for 6.5 hr after ranitidine treatment (two-way crossover).
2) Nine healthy volunteers were studied for the effect of metoclopromide (MCP) and anisotropine methylbromide (ATMB) (three-way crossover).
Ranitidine treatment resulted in a significant decrease in the parameters: k_a (from 0.957±0.052l/hr to 0.612±0.030l/hr; P<0.05); C_max (from 1.44±0.05μg/ml to 0.67±0.04μg/ml; P<0.01); AUC (from 7.33±0.40μghr/ml to 4.10±0.13μg hr/ ml; P<0.01); the amount of urinary excretion (37.75±0.72% to 21.07±1.82%: P< 0. 01). This indicates that the absorption of CS-807 is affected probably by the increased gastric pH and by the decrease of the dissolution of CS-807 in the stomach.
In contrast to the effect of ranitidine, no significant difference was found for the pharmacokinetic parameters of R-3763 among the groups of MCP, ATMB, and the control, except for the amount excreted into the urine between MCP (31.32±1.84%) and ATMB groups (39.80±3.18%) (P<0.05).
From these results, a sufficient low gastric pH and delayed gastric emptying time should be required for better absorption of CS-807 in man.