Intrathecal penetration of N-formimidoyl thienamycin in normal rabbits: potentiation by coadministration of renal dipeptidase enzyme inhibitor.
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.
D000818:Animals; D000900:Anti-Bacterial Agents / Q000134:cerebrospinal fluid*; D015377:Cilastatin; D003521:Cyclopropanes / Q000008:administration & dosage / Q000494:pharmacology*; D004150:Dipeptidases / Q000037:antagonists & inhibitors*; D004357:Drug Synergism; D005260:Female; D015378:Imipenem; D007668:Kidney / Q000201:enzymology; D008581:Meningitis / Q000188:drug therapy; D011817:Rabbits; D013845:Thienamycins / Q000008:administration & dosage / Q000134:cerebrospinal fluid*
D000900:Anti-Bacterial Agents; D003521:Cyclopropanes; D013845:Thienamycins; D015377:Cilastatin; D015378:Imipenem; D004150:Dipeptidases