Bioavailability and Metabolism of Talampicillin

Abstract

Talampicillin is an ester of ampicillin which is readily hydrolysed on absorption to release ampicillin. It is well absorbed from the gastro-intestinal tract resulting in a greater bioavailability of ampicillin than can be achieved with equivalent doses of ampicillin itself. Dose response studies have confirmed a direct relationship between the dose of talampicillin administered and peak serum ampicillin concentration and urinary excretion of ampicillin. Dosing of ampicillin after food has been shown to adversely affect the total bioavailability of ampicillin. This is not so after dosing with talampicillin. The bioavailability of ampicillin from a 250-mg Talpen® tablet dosed after a large meal was significantly greater than that from 250 mg ampicillin dosed in the fasting state. Studies in volunteer subjects at multiples of the proposed therapeutic dose for periods of up to 28 days have indicated its acceptability, bioavailability and lack of side effects on repeated dosing. The fate of the phthalidyl moiety of talampicillin has been investigated in repeated dose studies and in a single dose study in which radiolabelled talampicillin was administered. The principal metabolite of the phthalidyl moiety in man has been shown to be 2-hydroxymethylbenzoic acid, which is identical to that in experimental animals used for toxicological investigations.

Bioavailability of Bacampicillin and Talampicillin, Two Oral Prodrugs of Ampicillin

“…The serum concentrations found in this study are, in general, compatible with previous reports (4)(5)(6)(7)(8). The coefficient of variation in individual peak serum concentrations of approximately 20% after all doses is in agreement with previous results with bacampicillin (7,8), pivampicillin (8), and talampicillin (9), verifying a uniform and reliable absorption of these prodrugs.…”

Pharmacokinetic study of lenampicillin (KBT-1585) in healthy volunteers

“…A decrease in the Cmax and a delay in the Tmax have been shown; however, AUC and urinary recovery were not reduced significantly (6)(7)(8)12). It is therefore considered that the bioavailability of talampicillin is not changed by food (6)(7)(8). Bacampicillin is also not considered to be affected by food (10).…”

“…It has been observed that the absorption of pivampicillin is reduced when it is administered with a standard breakfast consisting of dairy products as well as eggs, sausage, toast, and milk, resulting in decreased AUC by almost half compared with that obtained in a fasting state (4). The interaction of talampicillin with food has also been well studied (6)(7)(8)12). A decrease in the Cmax and a delay in the Tmax have been shown; however, AUC and urinary recovery were not reduced significantly (6)(7)(8)12).…”

“…The interaction of talampicillin with food has also been well studied (6)(7)(8)12). A decrease in the Cmax and a delay in the Tmax have been shown; however, AUC and urinary recovery were not reduced significantly (6)(7)(8)12). It is therefore considered that the bioavailability of talampicillin is not changed by food (6)(7)(8).…”