Single- and multiple-dose pharmacokinetics of lenampicillin (KBT-1585) in healthy human subjects: comparative studies with amoxicillin.

Lenampicillin (LAPC) is a novel prodrug of ampicillin (ABPC) which is under development by KANEBO Ltd. and TORII Pharmaceutical Co. The single- and multiple-dose pharmacokinetic studies were performed on six healthy male volunteers. Amoxicillin (AMPC) was used as control drug. The oral single-dose studies of LAPC (equivalent to 250 mg ANPC) and of AMPC (500 mg) demonstrated that the mean peak serum concentrations of ABPC and AMPC were 11.4 +/- 0.8 micrograms/ml at 40 min and 8.5 +/- 0.7 micrograms/ml at 50-90 min, respectively. The half-lives and the areas under the concentration-time curves were the same for both antibiotics on an equimolar basis. The oral multiple-dose studies of LAPC and AMPC (twice a day for 8 days with the same single dose as above) showed that no measurable accumulation and no remarkable variations between the single- and multiple-dose pharmacokinetics were observed. No adverse effects were recorded for any subject. LAPC proved to have unique pharmacokinetic properties as compared with AMPC and high safety, and its further development to clinical trials appears warranted.