Intrathecal penetration of N-formimidoyl thienamycin in normal rabbits: potentiation by coadministration of renal dipeptidase enzyme inhibitor

Abstract

The intrathecal penetration of N-formimidoyl thienamycin (MK0787) with or without coadministration of the renal dipeptidase enzyme inhibitor (MK791) in normal rabbits was studied immediately before and after the third dose of 40 mg/kg infused intravenously at daily 6-h intervals. Mean +/- standard error peak concentrations in cerebrospinal fluid were 0.23 +/- 0.02 and 0.53 +/- 0.12 micrograms/ml without and with coadministration of MK791, respectively (P less than 0.05, Student's t test). Penetration into cerebrospinal fluid (based on the ratio of cerebrospinal fluid to plasma area under the concentration-time curves) were 4.4 and 6.0%, respectively. N-Formimidoyl thienamycin penetrated uninflamed meninges, and peak concentrations were significantly augmented by coadministration of MK791.