Phase 1 Study of the Safety, Tolerability, and Pharmacokinetics of Biapenem in Healthy Adult Subjects

Abstract

The pharmacokinetics and safety of biapenem were studied in 36 healthy adult subjects in a randomized, placebo-controlled, double blind, sequential single- and multiple-ascending-dose study using doses from 250 to 1,250\u2009mg administered three times a day using 3-h infusions. Maximum concentrations for biapenem were achieved at the end of the 3-h infusion. ABSTRACT The pharmacokinetics and safety of biapenem were studied in 36 healthy adult subjects in a randomized, placebo-controlled, double blind, sequential single- and multiple-ascending-dose study using doses from 250 to 1,250\u2009mg administered three times a day using 3-h infusions. Maximum concentrations for biapenem were achieved at the end of the 3-h infusion. Biapenem exposure (area under the curve [AUC]) increased in a slightly greater-than-dose-proportional manner after single and multiple doses with no evidence of accumulation with multiple doses. Plasma AUCs increased from 18\u2009mg · h/liter at 250\u2009mg to 150\u2009mg · h/liter at 1,250\u2009mg. Urinary recovery ranged from 14.2% at 250\u2009mg to 42.3% at 1,250\u2009mg. Biapenem was well tolerated up to 1,000\u2009mg administered every 8\u2009h by a 3-h infusion for 7\u2009days; however, higher incidences of nausea, vomiting, and rash were reported at 1,250\u2009mg. There were no serious adverse events (AEs) reported after either single or multiple doses of biapenem, and all AEs were mild or moderate in severity. (This study has been registered at ClinicalTrials.gov under registration no. NCT01702649.)