Pharmacokinetics in nonhuman primates of a prototype carbapenem active against methicillin-resistant Staphylococcus aureus.
Pharmacokinetic parameters were determined for imipenem-cilastatin and a carbapenem antibiotic, L-695,256, active against methicillin-resistant Staphylococcus aureus in rhesus monkeys and a chimpanzee. L-695,256 had larger areas under the concentration-time curve than imipenem-cilastatin (30 +/- 5 versus 24 +/- 1 micrograms.h/ml in the rhesus monkeys and 77 versus 60 micrograms.h/ml in the chimpanzee) and a longer half-life at beta phase (1.2 +/- 0.1 versus 0.6 +/- 0.1 h in the rhesus monkeys and 1.0 versus 0.8 h in the chimpanzee). Resistance to hydrolysis by the renal dehydropeptidase-I allowed L-695,256 to be administered as a single agent.
Sundelof
J G
JG
Department of Antibiotic Discovery and Development, Merck Research Laboratories, Rahway, New Jersey 07065, USA. jon-sundelof@merck.com
Thompson
R
R
White
K M
KM
Sasor
M W
MW
Cama
L
L
Kropp
H
H
D000818:Animals; D000900:Anti-Bacterial Agents / Q000493:pharmacokinetics*; D015780:Carbapenems / Q000493:pharmacokinetics; D015377:Cilastatin / Q000493:pharmacokinetics; D000077728:Cilastatin, Imipenem Drug Combination; D004150:Dipeptidases / Q000378:metabolism; D004338:Drug Combinations; D004359:Drug Therapy, Combination / Q000493:pharmacokinetics; D006207:Half-Life; D007093:Imidazoles / Q000493:pharmacokinetics; D015378:Imipenem / Q000493:pharmacokinetics; D007275:Injections, Intravenous; D007668:Kidney / Q000201:enzymology; D008253:Macaca mulatta; D008297:Male; D016106:Methicillin Resistance; D002679:Pan troglodytes; D013211:Staphylococcus aureus / Q000187:drug effects*
D000900:Anti-Bacterial Agents; D015780:Carbapenems; D004338:Drug Combinations; D007093:Imidazoles; C093180:L 695256; D015377:Cilastatin; D015378:Imipenem; D000077728:Cilastatin, Imipenem Drug Combination; D004150:Dipeptidases; C038937:dipeptidase