von Bergmann K, Laeis P, Püchler K, Sudhop T, Schwocho L R, Gonzalez L
Abteilung für Klinische Pharmakologie der Universität Bonn, Germany.
J Hypertens Suppl. 2001 Jun;19(1):S33-40. doi: 10.1097/00004872-200106001-00005.
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).
奥美沙坦酯在老年高血压患者以及肾功能和肝功能不全患者中能迅速被吸收并转化为奥美沙坦，血浆中未检测到奥美沙坦酯本身。口服给药后的头几天内达到药代动力学稳态。在老年（65 - 75岁）患者中，每日一次服用80mg奥美沙坦酯，以及在高龄（≥75岁）高血压患者中每日服用10mg后，稳态Cmax和曲线下面积（AUC(0 - 24 h)）值与年轻患者（<46岁）相比高出多达44%。老年（12.8小时）和高龄患者（16.5小时）的稳态消除半衰期值也比年轻患者（分别为10.6和12.3小时）更长。在肾功能不全患者中，每日服用10mg奥美沙坦酯达到稳态后，Cmax和AUC(0 - 24 h)均随肌酐清除率（CLCR）降低而升高，肾清除率（CLR）随CLCR降低而下降。轻度（CLCR，40 - 59 ml/min）和中度（CLCR，20 - 30 ml/min）肾功能不全患者的稳态Cmax和AUC(0 - 24 h)值比健康受试者的值分别高出多达39%和82%。在轻度（Child - Pugh评分≤6）和中度（评分7 - 9）肝功能不全患者中每日单次口服10mg奥美沙坦酯后，Cmax通常与健康匹配受试者相似，但AUC分别增加了30%和48%，与健康受试者对照相比，绝对生物利用度值略有增加。奥美沙坦在尿液中的排泄也随肝功能损害程度增加，表明在这种疾病状态下存在代偿性排泄机制。由于老年和高龄患者以及轻度和中度肾功能和肝功能不全患者中血浆浓度（Cmax和AUC(0 - 24 h)）的升高比其他研究中每日服用80mg奥美沙坦酯后观察到的且耐受性良好的血浆浓度低几倍，因此不认为这些组需要调整剂量。然而，对于重度肾功能不全患者，应考虑较低的起始剂量，建议每日剂量不超过20mg（普通患者人群为每日40mg）。
