Pharmacokinetic studies on clavulanate potentiated ticarcillin in normal subjects and patients with renal insufficiency.
Pharmacokinetics of the novel combination of ticarcillin with the beta-lactamase inhibitor clavulanic acid (BRL 28500, Timentin, Betabactyl) was investigated in order to calculate the dose reduction factor (DRF) and elaborate dosage recommendations for patients with varying degrees of renal impairment. Serum and urine levels of ticarcillin and clavulanic acid have been determined following the i.v. application of 3.2 g and 5.2 g BRL 28500 consisting of 3.0 g and 5.0 g ticarcillin, respectively, and 0.2 g of clavulanic acid each. 10 healthy volunteers and 9 patients received the 5.2 g formulation, and 6 normal subjects and 9 patients the 3.2 g formulation. The pharmacokinetics of both components of BRL 28500 behave fairly similarly and provides the combination with a logic basis. The dose reduction factor, being 1 by definition in normal renal function, rises in final renal failure to 2-3 for clavulanic acid and to 4-5 for ticarcillin. A dosis reduction to 1/2-1/4 will roughly produce the same AUC in a patient with terminal renal insufficiency as the normal dosage in a healthy subject. The distribution volume of ticarcillin and clavulanic acid was found to be enlarged probably due to overhydration in this group of patients. The recovery of both BRL 28500 components decreased with impaired renal function. The recovery 6 h after administration of 0.2 g clavulanic acid in the 5.2 g (3.2 g) BRL 28500 formulation fell from 58 +/- 12% (52 +/- 6) in healthy subjects to 25 +/- 14% (25 +/- 13) in patients with renal insufficiency.(ABSTRACT TRUNCATED AT 250 WORDS)
D002969:Clavulanic Acids / Q000097:blood*; D004305:Dose-Response Relationship, Drug; D004338:Drug Combinations / Q000097:blood; D005919:Glomerular Filtration Rate; D006207:Half-Life; D006801:Humans; D007262:Infusions, Intravenous; D007676:Kidney Failure, Chronic / Q000097:blood*; D007700:Kinetics; D010406:Penicillins / Q000097:blood*; D013982:Ticarcillin / Q000097:blood*
D002969:Clavulanic Acids; D004338:Drug Combinations; D010406:Penicillins; C043215:ticarcillin-clavulanic acid; D013982:Ticarcillin