Ticarcillin clavulanate clinical pharmacology
Editor-In-Chief: C. Michael Gibson, M.S., M.D. [1]; Associate Editor(s)-in-Chief: Mohamed Moubarak, M.D. [2]
Clinical Pharmacology
- Absorption:
After an intravenous infusion (30 minutes) of 3.1 grams of TIMENTIN, peak serum concentrations of both ticarcillin and clavulanic acid were attained immediately after completion of the infusion. Ticarcillin serum levels were similar to those produced by the administration of equivalent amounts of ticarcillin alone with a mean peak serum level of 324 mcg/mL. The corresponding mean peak serum level for clavulanic acid was 8 mcg/mL. (See Table 2.)
The mean area under the serum concentration curve was 485 mcg•hr/mL for ticarcillin and 8.2 mcg•hr/mL for clavulanic acid.
- Distribution:
Ticarcillin has been found to be approximately 45% bound to human serum protein and clavulanic acid approximately 25% bound. Ticarcillin can be detected in tissues and interstitial fluid following parenteral administration. Distribution of ticarcillin into bile and pleural fluid has been demonstrated. The results of experiments involving the administration of clavulanic acid to animals suggest that this compound, like ticarcillin, is well distributed in body tissues.
- Elimination:
Approximately 60% to 70% of ticarcillin and approximately 35% to 45% of clavulanic acid are excreted unchanged in urine during the first 6 hours after administration of a single dose of TIMENTIN to normal volunteers with normal renal function. Two hours after an intravenous injection of 3.1 grams of TIMENTIN, concentrations of ticarcillin in urine generally exceed 1,500 mcg/mL. The corresponding concentrations of clavulanic acid in urine generally exceed 40 mcg/mL. By 4 to 6 hours after injection, the urine concentrations of ticarcillin and clavulanic acid usually decline to approximately 190 mcg/mL and 2 mcg/mL, respectively. The mean serum half‑life of both ticarcillin and clavulanic acid in healthy volunteers was 1.1 hours.
- Pediatrics:
In pediatric patients receiving approximately 50 mg/kg of TIMENTIN (30:1 ratio ticarcillin to clavulanate), mean ticarcillin serum half‑lives were 4.4 hours in neonates (n = 18) and 1.0 hour in infants and children (n = 41). The corresponding clavulanate serum half‑lives averaged 1.9 hours in neonates (n = 14) and 0.9 hour in infants and children (n = 40). Area under the serum concentration time curves averaged 339 mcg•hr/mL in infants and children (n = 41), whereas the corresponding mean clavulanate area under the serum concentration time curves was approximately 7 mcg•hr/mL in the same population (n = 40).
- Renal Impairment:
An inverse relationship exists between the serum half‑life of ticarcillin and creatinine clearance. The half‑life of ticarcillin in patients with renal failure is approximately 13 hours. The dosage of TIMENTIN need only be adjusted in cases of severe renal impairment [see Dosage and Administration (2.3)].
Ticarcillin may be removed from patients undergoing dialysis; the actual amount removed depends on the duration and type of dialysis.[1]
References
Adapted from the FDA Package Insert.