Pharmacokinetics and distribution of ticarcillin-clavulanic acid (Timentin) in experimental animals.
The pharmacokinetics and distribution of ticarcillin and clavulanic acid were studied in rats and rabbits after intravenous coadministration of the compounds. The elimination half-lives for ticarcillin and clavulanic acid were similar in both rats (ticarcillin, 0.22 h; clavulanic acid, 0.24 h) and rabbits (ticarcillin, 0.38 h; clavulanic acid, 0.31 h). Both compounds distributed widely throughout rat tissues, and the patterns of distribution were similar to those observed for other beta-lactams. Values for penetration into rat pleural, peritoneal, and subcutaneous fluids calculated from the equation (AUCfluid/AUCserum) X 100, where AUC is the area under the concentration-time curve, were between 83 and 93% for ticarcillin and 86 and 103% for clavulanic acid. Values for penetration into tissue cages in rabbits were 139% +/- 45% for ticarcillin and 109% +/- 22% for clavulanic acid. The penetration of clavulanic acid into rabbit cerebrospinal fluid was higher (P less than 0.05) (4.0% +/- 0.61%) than that of ticarcillin (1.3% +/- 0.53%). Overall, the results show that ticarcillin and clavulanic acid distribute readily throughout body tissues and fluids and predict that the penicillin and beta-lactamase inhibitor would be present together at sites of infection.
D000818:Animals; D001798:Blood Proteins / Q000378:metabolism; D002969:Clavulanic Acids / Q000134:cerebrospinal fluid / Q000493:pharmacokinetics*; D004338:Drug Combinations / Q000134:cerebrospinal fluid / Q000493:pharmacokinetics; D008297:Male; D010406:Penicillins / Q000493:pharmacokinetics*; D011485:Protein Binding; D011817:Rabbits; D051381:Rats; D013982:Ticarcillin / Q000134:cerebrospinal fluid / Q000493:pharmacokinetics*; D014018:Tissue Distribution; D065093:beta-Lactamase Inhibitors
D001798:Blood Proteins; D002969:Clavulanic Acids; D004338:Drug Combinations; D010406:Penicillins; D065093:beta-Lactamase Inhibitors; C043215:ticarcillin-clavulanic acid; D013982:Ticarcillin