The effects of gastric pH and food on the pharmacokinetics of a new oral cephalosporin, cefpodoxime proxetil

Abstract

The effects of alteration of gastric pH and food on the pharmacokinetics of 200 mg doses of cefpodoxime proxetil tablets were studied in two separate randomized, open label, crossover studies in healthy subjects. In the pH study (n = 17 subjects), there was a lead-in period done under fasting conditions, followed by randomization to a four-way crossover of pentagastrin (6 micrograms/kg, subcutaneously), ranitidine (150 mg orally, 10 and 2 hours before dosing with the antibiotic), sodium bicarbonate (12.6 gm), or aluminum hydroxide (120 cc). Gastric pH was determined by nasogastric aspirates before and 10 minutes after the intervention, just before the antibiotic was given. Peak plasma concentrations (Cmax) and area under plasma concentration-time curve (AUC) were highest in fasting and pentagastrin periods and were 35% to 50% lower for all of the other periods (p less than 0.0001). Gastric pH and Cmax and AUC were inversely related (r = 0.66 and r = 0.62; p less than 0.0001 for both). In the food study (n = 16 subjects), there were two lead-in periods, one done while subjects were fasting and one while they were normal diet, followed by randomization to a four-way crossover of either high or low protein diets, or high or low fat diets. There were six meals in each diet. Dosing with the antibiotic was done at the midpoint of the fourth meal. Cmax and AUC were 22% to 34% higher for all diets than for the fasting period (p less than 0.0001), whereas the time to Cmax was unchanged. These studies demonstrated that absorption of cefpodoxime proxetil is best at low gastric pH or in the presence of food, which suggests that the role of gastrointestinal function on the pharmacokinetic profile is complex.

Effect of food on absorption of cefpodoxime proxetil oral suspension in adults

“…Food has been shown to alter cefpodoxime bioavailability from tablets by increasing the extent of absorption of cefpodoxime proxetil (2,8). This food effect was not associated with meal composition because the increases in cefpodoxime bioavailability were similar in five equicaloric test meals which varied with respect to fat and protein content (8).…”

“…Food has been shown to alter cefpodoxime bioavailability from tablets by increasing the extent of absorption of cefpodoxime proxetil (2,8). This food effect was not associated with meal composition because the increases in cefpodoxime bioavailability were similar in five equicaloric test meals which varied with respect to fat and protein content (8). Administration of a cefpodoxime proxetil oral solution with food had no effect on the extent of drug absorption, suggesting that food may improve drug solubility from the tablet dosage form by facilitating drug dissolution and/or by retaining the tablet in the acidic environment of the stomach, where cefpodoxime proxetil is more soluble and stable (3).…”

“…Blood samples were collected in tubes containing EDTA anticoagulant at zero hour (prior to drug administration) and at 0.25, 0.50, 0.75, 1, 1.5, 2, 2.5, 3,4,6,8,10,12,16,20, and 24 h after dosing. Samples were immediately refrigerated and then were centrifuged at 2,060 ϫ g for 6 min at 4ЊC.…”

Gastro-retentive Dosage Form for Improving Bioavailability of Cefpodoxime Proxetil in Rats

“…1 3) The drug is absorbed throughout the gastrointestinal tract (GIT), and shows relatively higher bioavailability in fed conditions than fasted conditions. 4) The bioavailability of CP administered as a tablet relative to cefpodoxime sodium intravenous infusion is about 50％. 5) Although CP was developed to improve the permeability and thus bioavailability of the parent molecule CA, only 50％ of oral bioavailability is achieved.…”

Orally administered cefpodoxime proxetil for treatment of uncomplicated gonococcal urethritis in males: a dose-response study

“…Because 100% eradication of N. gonorrhoeae was achieved at each planned dose, probenecid was not given, and a 50-mg dose of CPD was evaluated instead. All patients received the medication after a light snack (3)(4)(5).…”