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

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.