Pharmacokinetics of N-formimidoyl thienamycin and influence of a renal dipeptidase inhibitor in experimental meningitis

J Antimicrob Chemother. 1983 Jul;12(1):39-45. doi: 10.1093/jac/12.1.39.

Abstract

We studied the pharmacokinetics of N-formimidoyl thienamycin with and without a renal dipeptidase inhibitor in plasma and cerebrospinal fluid (CSF) of rabbits. Thienamycin reached a maximal concentration of 0.6 +/- 0.06 mg/l in the CSF of normal rabbits. When the meninges were inflamed, the mean CSF concentration of N-formimidoyl thienamycin was 3.2 +/- 1.5 mg/l, five times higher than in normal rabbits. This concentration would kill most bacteria that cause meningitis. The renal dipeptidase inhibitor alone had no detectable antibacterial activity. When administered with N-formimidoyl thienamycin, it exerted only minor effects on the pharmacokinetics in either plasma or CSF of normal or infected rabbits.

MeSH terms

  • Animals
  • Anti-Bacterial Agents / metabolism*
  • Dipeptidases / antagonists & inhibitors*
  • Imipenem
  • Kidney / enzymology*
  • Kinetics
  • Meningitis, Haemophilus / metabolism*
  • Rabbits
  • Thienamycins / metabolism*

Substances

  • Anti-Bacterial Agents
  • Thienamycins
  • Imipenem
  • Dipeptidases