Pharmacokinetics of cerivastatin in renal impairment are predicted by low serum albumin concentration rather than by low creatinine clearance

The influence of renal impairment on the clearance of the new HMG-CoA reduc tase inhibitor cerivastatin was evaluated. A single oral dose of 300 mu g c erivastatin was given to 18 patients with different degrees of renal impair ment and 6 healthy controls. Concentrations of total cerivastatin, its frac tion unbound, and the total concentrations of the active metabolites M1 and M23 were measured in plasma. Serum concentrations of unbound cerivastatin were calculated for each individual from the concentration of total cerivas tatin and cerivastatin's fraction unbound at t = 2.5 hours. In contradictio n to what had been expected, renal impairment significantly influenced the pharmacokinetics of cerivastatin. The best correlation to the AUC and C-max of unbound cerivastatin was found with serum albumin concentration. Also, serum albumin concentration was the only factor significantly correlated to t(1/2) of cerivastatin. Significant but slighter correlation with the AUC and C-max of unbound cerivastatin was also observed for creatinine clearanc e and cerivastatin's fraction unbound: while no correlation was observed wi th total plasma protein. No significant correlation of creatinine clearance , serum albumin concentration, f(u), or total plasma protein concentration with the AUC and C-max of total cerivastatin or the AUC, C-max, or t(1/2) o f M1 and M23 was observed. The authors conclude that low serum albumin conc entration rather than low creatinine clearance predicts the pharmacokinetic s of cerivastatin in renal impairment. (C) 1999 the American College of Cli nical Pharmacology.