Absorption, distribution, metabolism and excretion of talampicillin hydrochloride. (1) Dose-response relationship and effects of food intake on its metabolism

Abstract

Absorption and urinary excretion of a new ampicillin derivative, talampicillin hydrochloride, were studied.The peak concentrations of ampicillin in plasma of mice and rats after oral administration of talampicillin hydrochloride were much higher than those after ampicillin administration. A peak in plasma concentration was observed 15 minutes after administration of talampicillin hydrochloride in mice and 30 minutes in rats, whereas the concentration reached a peak 30 minutes after ampicillin administration in both species. An average area under the plasma concentration curves for talampicillin hydrochloride was approximately 5 times greater than that for ampicillin in mice and was 3 times greater in rats, indicating better absorption of talampicillin hydrochloride in both animals.Talampicillin hydrochloride or ampicillin with 125 mg and 250 mg was orally given to fasting volunteers. The absorption of talampicillin hydrochloride was twice as better as that of ampicillin. Approximately 50% of the given amount of talampicillin hydrochloride was recovered in the urine, whereas 30% was recovered when ampicillin was given.To determine the effect of food on the oral absorption of talampicillin hydrochloride, 10 subjects received 250 mg doses in fasting and then post-prandial state with one week interval. Neither the peak plasma concentration nor the total amount of urinary excretion during 6 hours was influenced by food. But the peak plasma concentration was seen 1 hour after when talampicillin hydrochloride was given in fasting state, in contrast to 2 hours when given in post-prandial state. The majority of ampicillin in urine was excreted during the first 2 hours in fasting state, in contrast to 2 to 4 hours in post-prandial state.