Effect of saturable clearance during high-dose mezlocillin therapy.
As mezlocillin has been shown to display nonlinear pharmacokinetics in single-dose evaluations, we evaluated a crossover trial in patients with renal dysfunction the impact on serum clearance of fixed-dose versus fixed-interval administration of identical daily doses of the drug. In four patients with creatinine clearances of 0.00 to 1.78 liters/h per 1.73 m2, equal serum clearances were observed when the calculated daily total dose of mezlocillin was given either as a fixed dose of 5,000 mg at various intervals or every 4 h at various doses. We found that repetitive large daily doses that are equivalent to 30 g/day in patients with normal renal function can be administered to patients with impaired renal function as a reduced dose every 4 h instead of prolonging the dosing interval, as suggested by Mangione et al. (Antimicrob. Agents Chemother. 21:428-435, 1982). The observed serum clearances were equal for the two schedules, probably owing to the degree of continuing saturation of the nonlinear clearance mechanisms of mezlocillin.
D000328:Adult; D000368:Aged; D005260:Female; D006801:Humans; D007674:Kidney Diseases / Q000503:physiopathology; D007700:Kinetics; D008297:Male; D008802:Mezlocillin / Q000097:blood / Q000627:therapeutic use*; D008875:Middle Aged
D008802:Mezlocillin