Olmesartan medoxomil: influence of age, renal and hepatic function on the pharmacokinetics of olmesartan medoxomil

Olmesartan medoxomil was rapidly absorbed and converted to olmesartan in elderly hypertensive patients, and in patients with renal and hepatic dysfunction. No olmesartan medoxomil itself was detected in plasma. Pharmacokinetic steady state was reached within the first few days after oral dosing. In elderly (65-75 years old), after 80 mg olmesartan medoxomil once daily, and very elderly (> or = 75 years old) hypertensive patients after 10 mg daily, steady-state Cmax and area under the curve (AUC(0-24 h)) values were up to 44% higher compared with young patients (< 46 years). Steady-state elimination half-life values were also longer in elderly (12.8 h) and very elderly patients (16.5 h) compared with young patients (10.6 and 12.3 h, respectively). At steady state after 10 mg olmesartan medoxomil daily in patients with renal impairment, both Cmax and AUC(0-24 h) increased as creatinine clearance (CLCR) decreased, and renal clearance (CLR) decreased with decreasing CLCR. Steady-state Cmax and AUC(0-24 h) values in patients with mild (CLCR, 40-59 ml/min) and moderate (CLCR, 20-30 ml/min) were up to 39 and 82% higher than the values in healthy subjects. After single oral doses of 10 mg olmesartan medoxomil daily to patients with mild (Child-Pugh score < or = 6) and moderate (score 7-9) hepatic impairment, Cmax was generally similar to that in healthy matched subjects, but AUC increased by 30 and 48%, respectively, and was reflected in small increases in absolute bioavailability values compared with healthy subject controls. Excretion of olmesartan in urine also increased with the degree of hepatic impairment, indicating a compensatory excretion mechanism in this disease state. Since the increased plasma concentrations (Cmax and AUC(0-24 h)) in elderly and very elderly patients, and in mild and moderate renal and hepatic impairment, were several-fold lower than plasma concentrations observed in other studies after 80 mg olmesartan medoxomil daily that were well tolerated, a dosing adjustment in these groups is not considered necessary. In patients with severe renal impairment, however, consideration should be given to a lower starting dose, and it is recommended that the daily dose should not exceed 20 mg daily (compared with 40 mg daily for the general patient population).