Pharmacokinetics of vancomycin and dosage planning in patients with renal insufficiency

We assessed the pharmacokinetics and dosage regimen of vancomycin in patients with renal insufficiency. 1) Vancomycin (VCM), 500 mg, was administered to healthy volunteers and patients with varying degrees of impaired renal function by 60-minute drip infusion. Serum levels of VCM after a single dose were assayed by FPIA and urinary levels by bioassay. Pharmacokinetic parameters were determined using a two-compartment model. In healthy volunteers, mean T^1/2(β) was 3.08h and mean β was 0.233/h. As the degree of renal insufficiency became more severe, T^1/2(β) became more prolonged and β decreased. The mean 24-h urinary excretion rate was 96.3% in the healthy volunteers and decreased in accordance with the severity of the renal insufficiency. 2) To plan the dosage regimen, β was selected as a parameter which varied in accordance with the degree of impaired renal function as determined on the basis of creatinine clearance. The appropriateness of this regimen was confirmed in a multiple-dose study.