Open AccessIntrathecal penetration of N-formimidoyl thienamycin in normal rabbits: potentiation by coadministration of renal dipeptidase enzyme inhibitor
Author(s) -
A W Chow,
K R Finlay,
H Grant Stiver,
Chelsea Carlson
Publication year - 1983
Publication title -
antimicrobial agents and chemotherapy
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 2.07
H-Index - 259
eISSN - 1070-6283
pISSN - 0066-4804
DOI - 10.1128/aac.23.4.634
Subject(s) - thienamycin , chemistry , cerebrospinal fluid , pharmacology , penetration (warfare) , intrathecal , pharmacokinetics , anesthesia , medicine , biochemistry , antibiotics , operations research , engineering
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.