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.
D000818:Animals; D000900:Anti-Bacterial Agents / Q000378:metabolism*; D004150:Dipeptidases / Q000037:antagonists & inhibitors*; D015378:Imipenem; D007668:Kidney / Q000201:enzymology*; D007700:Kinetics; D008583:Meningitis, Haemophilus / Q000378:metabolism*; D011817:Rabbits; D013845:Thienamycins / Q000378:metabolism*
D000900:Anti-Bacterial Agents; D013845:Thienamycins; D015378:Imipenem; D004150:Dipeptidases