Pharmacokinetics of the combination of ticarcillin with clavulanic acid in renal insufficiency.

The pharmacokinetics of ticarcillin and clavulanic acid were studied by blood and urine assay methods in 25 patients divided into five groups with varying degrees of renal insufficiency i.e. mild, moderate and severe renal insufficiency, almost anuric patients and those requiring haemodialysis (groups A to E). A single dose of 5.2 g Timentin (5.0 g ticarcillin and 200 mg clavulanic acid) was administered intravenously by infusion over 30 min. The average elimination half-life (T1/2) of ticarcillin increased from 0.95 h in patients with creatinine clearance (Clcr) of 80 ml/min to 1.8, 4.4, 6.9 and 11.2 h respectively in mild, moderate and severe renal insufficiency and in almost anuric patients. The T1/2 values for clavulanic acid were 0.75, 0.9, 2.0, 2.5 and 4.8 h in the same groups. The area under concentration-time curve (AUC) for ticarcillin increased from 787 to 2839 mg/l/h and for clavulanic acid from 12.8 to 29 mg/l/h when group mean values from patients with mild and severe renal insufficiency were compared. The plasma clearance (Clpl) of clavulanic acid was in all groups greater than that of ticarcillin i.e. 166 and 100 ml/min vs. 79.2 and 25.0 ml/min when comparing mean values from groups with mild and severe renal insufficiency respectively. The plasma clearance ratio clavulanic acid/ticarcillin increased proportionally to the degree of renal insufficiency from a value of 1.5 in normal subjects to between 3.3 and 3.8 in more advanced cases.(ABSTRACT TRUNCATED AT 250 WORDS)