Pharmacokinetics of troglitazone in patients with renal insufficiency

Objective: The pharmacokinetic profiles of troglitazone and two metabolites were evaluated following a single 400mg oral dose of troglitazone in 20 pa tients with various degrees of renal function. Methods: Plasma troglitazone and metabolite concentrations were determined by high performance liquid chromatography, and troglitazone free fraction w as determined by ultracentrifugation. Results: Mean maximum plasma concentration and area under the curve for tot al troglitazone appeared lower in patients with severe renal impairment (SR I) compared with those with normal renal function (NRF). Troglitazone free fraction was higher in patients with SRI (4.85%) than in subjects with NRF (1.66%), producing similar exposure values for unbound troglitazone, the mo iety presumed to exert the pharmacological effect. Regression analysis reve aled poor correlations of creatinine clearance value with total troglitazon e, unbound troglitazone, and metabolite pharmacokinetic parameter values. Conclusion: These data indicated that renal function does not predict trogl itazone pharmacokinetics and systemic exposure to unbound troglitazone is u naltered with renal impairment. Thus, troglitazone dose adjustment based on pharmacokinetics is not required in patients with renal insufficiency.