Influence of an antacid containing aluminum and magnesium on the pharmacokinetics of cefixime

Abstract

Interaction studies in dogs have indicated that antacids significantly decrease the oral bioavailablity of cefixime. Twelve healthy adult male volunteers participated in a randomized, four-way crossover trial to evaluate the influence of an aluminum-magnesium antacid (Maalox; 20 ml) on the pharmacokinetics of cefixime (400 mg). Regimens were (i) cefixime alone; (ii) cefixime simultaneous with antacid; (iii) cefixime 2 h before antacid; and (iv) cefixime 2 h after antacid. Serial blood and urine samples were collected over a 24-h period following each dose of cefixime. There was a 1-week washout interval between regimens. Cefixime concentrations in serum and urine were analyzed by high-performance liquid chromatography. Maximum cefixime concentrations in serum for regimens i through iv were (mean ± standard deviation) 4.9 ± 1.4, 5.7 ± 1.3, 5.1 ± 1.0, and 5.5 ± 1.5 ,ug/ml, respectively. Corresponding values for area under the serum concentration-time curve extrapolated to infinity were 38.3 ± 14.5, 42.8 ± 13.9, 38.5 ± 9.8, and 41.6 ± 16.7 ,ug-h/ml. There was a trend toward increased concentrations in serum and area under the curve of cefixime when it was administered concomitantly with antacid; however, these differences were not statistically significant (P > 0.05; analysis of variance). We conclude that single-dose administration of an aluminum-magnesium antacid does not significantly decrease the oral bioavailability of cefixime.Nonsystemic antacids containing aluminum and magnesium are widely used in the treatment of gastrointestinal disorders. Coadministration of antacids has been found to interfere with the absorption of many drugs, including tetracyclines, cefuroxime axetil, and fluoroquinolone antibiotics (1,6,10,12).Cefixime is an investigational oral cephalosporin that has good in vitro activity against a broad range of respiratory and urinary tract pathogens and is very stable against various P-lactamases (9). It has an absolute bioavailability of 40 to 52%, and food does not interfere with the overall extent of drug absorption (3)(4)(5) Washington, Pa.). Regimens were (i) cefixime alone, (ii) cefixime simultaneous with antacid, (iii) cefixime 2 h before antacid, and (iv) cefixime 2 h after antacid. All doses of cefixime were administered as one 400-mg tablet followed by 240 ml of water, and each dose of antacid was administered as a 20-ml of suspension. Nov. 1989Nov. , p. 1994Nov. -1997 1, 1.5, 2, 2.5, 3, 3.5, 4, 5, 6, 8, 12, and 24 h postdose. After coagulation and centrifugation, the separated serum was stored frozen at -70°C until assayed. Urine was collected during the intervals from -2 to 0 (baseline), 0 to 2, 2 to 4, 4 to 6, 6 to 8, 8 to 12, and 12 to 24 h postdose. The total volume of urine within each interval was recorded, the pH was measured, and a 10-ml portion of each sample was frozen at -70°C until analyzed. Serum and urine samples were assayed within 6 weeks. Cefixime assay. Cefixime concentrations in serum and urine were measured by reversed-phase high-performance liquid chromatogra...

Effect of antacid on the bioavailability of cefprozil

“…The decrease in bioavailabilities of both prodrug esters of these cephalosporins are thought to be due to decreased drug dissolution with raised gastric pH. Concurrent administration of an antacid does not significantly affect the pharmacokinetic parameters of some other P-lactam antibiotics such as amoxicillin (7), cephalexin (7), cefixime (10,14), or cefetamet pivoxil (5).…”

“…Coadministration of antacids and antibiotics has affected the bioavailabilities of some antibiotics (7,11,13,21) but not others (5,7,10,14). This Subjects.…”

Formulation and Evaluation of Controlled Release Floating Tablets of Cefixime Using Hydrophilic Polymers

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Magnesium Hydroxide/Aluminium Hydroxide‐Containing Antacid Does Not Affect the Pharmacokinetics of the Targeted Phosphodiesterase 4 Inhibitor Roflumilast

“…Balanced mixtures of magnesium hydroxide and aluminium hydroxide are widely used as nonprescription antacids for the symptomatic treatment of hyperacidity‐associated gastric symptoms and complications 9 . Antacids are known for their potential to interfere with the absorption of many drugs, including chloroquine, itraconazole, and fluoroquinolone antibiotics 10–17 …”