Effect of cimetidine on the absorption of orally administered tetracycline.

Abstract

1 Six healthy female subjects received orally two 250 mg tetracycline tablets either with 400 mg cimetidine or placebo. In a separate experiment six healthy female volunteers received 500 mg tetracycline as a suspension on the fifth day of a 6 day regime of 400 mg cimetidine or placebo, 8 hourly and at bedtime. 500 mg tetracycline as tablets was also given with cimetidine only. 2 Following a single dose of cimetidine the mean peak tetracycline plasma concentration was significantly reduced by 1.2 microgram/ml and the area under the plasma concentration, time curve was decreased by 40%. The 72 h urinary tetracycline excretion was diminished by approximately 30%. 3 Tetracycline had no effect on the plasma concentration, time profile of cimetidine. 4 Administration of 400 mg cimetidine 8 hourly and at night for 6 days and dosing with 500 mg tetracycline as tablets or suspension on the fifth day produced no alteration in tetracycline kinetics. 5 It was concluded that under clinical circumstances it is unlikely that cimetidine produces a clinically significant alteration in tetracycline absorption or disposition. 6 The bioavailability of tetracycline from tablets and suspension was found to be similar (31.2% and 36.9% of the dose excreted in the urine over 72 h). 7 The mean renal clearance of tetracycline was 83.8 ml/min (95% confidence interval +/‐ 9.2 ml/min) and was unaltered by cimetidine treatment.

Drug Interactions with Cimetidine

“…In the same study design as that described for ampicillin (section 1.4), the subjects took co-trimoxazole (160mg trimethoprim plus 800mg sulphamethoxazole) with and without cimetidine (Rogers et al, 1980). Again, no significant differences in the pharmacokinetics of sulphamethoxazole or trimethoprim were observed, although plasma concentrations of the latter tended to be higher under cimetidine treatment.…”

“…In I study a 400mg dose of cimetidine reduced the absorption of tetracycline (as measured by the area under the plasma concentration-time curve, and urinary excretion) by between 30 and 40 %. However, chronic dosing with cimetidine for 5 days had no effect on tetracycline disposition (Fisher et al, 1980). In another study, chronic treatment with cimetidine reduced the absorption of tetracycline (as measured by urinary excretion) from a capsule formulation by an average of 30 %, but had no effect when tetracycline was given in solution form (Cole et al, 1980).…”

“…Six normal healthy subjects received 400mg of cimetidine or placebo every 6 hours, and on the sixth day 500mg of ampicillin (Rogers et al, 1980). As assessed by the peak plasma concentration, the time of its occurrence, the area .under the plasma concentration-time curve and the terminal half-life, cimetidine induced no alterations in ampicillin disposition.…”

The effect of intravenous cimetidine on the absorption of orally administered diazepam and lorazepam.

“…Morrison et al (1980) found that although the coating should be soluble at pH 5 to 7, the bioavailabilty of prednisolone from an enteric-coated formulation was not affected by cimetidine under circumstances similar to those in which both drugs would be used by patients. Fisher et al (1980) found reduced absorption of tetracycline with singles dose administration, but Garty & Hurwitz (1980) did not find this with chronic administration. To complicate matters, Breckenridge et al (1979) found that cimetidine increased the action of warfarin in man by inhibition of drug metabolism.…”

Concurrent administration of cimetidine and enteric‐coated prednisolone: effect on plasma levels of prednisolone.

“…We have, however, failed to demonstrate a clinically significant effect on the absorption of orally administered tetracycline (Fisher, House, Inns, Morrison, Rogers & Bradbrook, 1980). A preliminary report by Sternberg, King & Toskes (1978) has described inhibition of the absorption of Concurrent administration of food does not affect the absorption of enteric-coated prednisolone (Lee, Taylor, Walker & James, 1979).…”