Pharmacokinetic drug interaction study: administration of ceftibuten concurrently with the antacid mylanta double- strength liquid or with ranitidine.
This study investigated the influence of antacid (Mylanta Double-Strength Liquid; J & J-Merck Consumer, Fort Washington, PA) and the H2 antagonist ranitidine on the pharmacokinetics of ceftibuten, a once-daily oral cephalosporin. Eighteen male volunteers received, in a randomized, three-way, crossover design, a single oral 400-mg dose of ceftibuten after an overnight fast (1) alone, (2) with antacid (60 mL), and (3) with ranitidine (after 3 days of dosing, 150 mg/12 hours). Serial blood and urine samples were collected during a 24-hour period after each administration, with a 1-week washout between treatments. Ceftibuten, and its metabolite ceftibuten-trans, were analyzed in plasma and urine by high-performance liquid chromatography. Bioavailability parameters, maximum plasma concentration and area under the plasma concentration-time curve to infinity of ceftibuten were unaffected by treatment with antacid. These parameters were somewhat higher when ceftibuten was administered with ranitidine, but they were still within the ranges seen in normal healthy volunteers. The excretion of ceftibuten was independent of treatment. The concentrations of ceftibuten-trans were low in both plasma and urine with all three treatments. It is concluded that the co-administration of antacid and ranitidine are unlikely to affect the bioavailability and antibacterial efficacy of ceftibuten.
Radwanski
E
E
Department of Drug Metabolism and Pharmacokinetics, Schering-Plough Research Institute, Kenilworth, NJ 07033, USA.
Nomeir
A
A
Cutler
D
D
Affrime
M
M
Lin
C C
CC
D000284:Administration, Oral; D000328:Adult; D000536:Aluminum Hydroxide / Q000493:pharmacokinetics*; D000863:Antacids / Q000493:pharmacokinetics*; D000897:Anti-Ulcer Agents / Q000493:pharmacokinetics*; D001682:Biological Availability; D000077722:Ceftibuten; D002511:Cephalosporins / Q000008:administration & dosage / Q000378:metabolism / Q000493:pharmacokinetics*; D002851:Chromatography, High Pressure Liquid; D018592:Cross-Over Studies; D004338:Drug Combinations; D004347:Drug Interactions; D016903:Drug Monitoring; D004359:Drug Therapy, Combination; D006801:Humans; D008276:Magnesium Hydroxide / Q000493:pharmacokinetics*; D008297:Male; D008657:Metabolic Clearance Rate; D011899:Ranitidine / Q000493:pharmacokinetics*; D012841:Simethicone / Q000493:pharmacokinetics*; D013997:Time Factors
D000863:Antacids; D000897:Anti-Ulcer Agents; D002511:Cephalosporins; D004338:Drug Combinations; C008570:aluminum hydroxide, magnesium hydroxide, simethicone drug combination; D000536:Aluminum Hydroxide; D012841:Simethicone; D011899:Ranitidine; D000077722:Ceftibuten; D008276:Magnesium Hydroxide