Pharmacokinetic Studies of Serum Levels and Urinary Excretion of Ticarcillin after Intravenous and Intramuscular Administration to Patients with Normal and Abnormal Renal Function
The pharmacokinetics of ticarcillin after intravenous and intramuscular administration were determined. In individuals with CCr >60 ml/min, the T1/2 was 71±6 minutes after intravenous administration. Patients with CCr 30-60 ml/min had a T1/2 of 3.0 ± 0.6 hours. The T1/2 in patients with CCr 10-30 ml/Tin was 8.5± 2.1 hours, and inthose with CC r < 10 ml/min, 14.8 ± 3.7 hours. Combined hepatic and renal failure increased the T1/2 to 27.8 hours. Intramuscular administration of ticarcillin pro-duced adequate urine levels in patients with normal renal function and therapeutic serum levels in those with renal failure. Urinary concentrations of ticarcillin during intravenous therapy were adequate at all levels of renal function. Ticarcillin was well cleared by hemodialysis with a T1/2 of 3.1 ± 0.8 hours; peritoneal dialysis was minimally effective.’ A program for the use of ticarcillin in renal failure is presented.
The introduction of carbenicillin in 1967 (Acred et al, 1967) proved to be an important advance in the therapy of serious infec?tions due to certain members of the Enterobacteriaceae and Ps. aeruginosa. In vitro studies of a thienyl penicillin derivative, ticarcillin (Neu and Winshell, 1970), showed this compound was twice as active as carbenicillin against Pseudomonas. Preliminary studies by several investigators (Rodriguez et al, 1973; Wise and Reeves, 1974) and by our own group (Parry and Neu, in preparation) have shown this agent to be effective in the treatment of serious gram negative infections. Since ticarcillin will be used to treat infections occurring in individuals with impaired renal function, we investigated the pharmacokinetics of ticarcillin in normal volunteers and in patients with varying degrees of renal insufficiency as well as in patients undergoing hemodialysis and peritoneal dialysis.
KeywordsPeritoneal Dialysis Creatinine Clearance Normal Renal Function Urinary Concentration Blood Flow Rate
Unable to display preview. Download preview PDF.
- Davies, M.,Morgan, J.R. and Anand, C. (1974) Chemotherapy, 20, 339–341.Google Scholar
- Neu, H.C. and Swarz, H. (1970) Journal of General Microbiology, 58, 301–305.Google Scholar
- Neu, H.C. and Winshell, E.B. (1970) Antimicrobial Agents and Chemotherapy, 385–389.Google Scholar
- Rodriguez, V., Bodey, G.P., Horikoshi, N., Inagaki, J. andGoogle Scholar