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首页> 美国卫生研究院文献>Antimicrobial Agents and Chemotherapy >Oseltamivir and Oseltamivir Carboxylate Pharmacokinetics in Obese Adults: Dose Modification for Weight Is Not Necessary
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Oseltamivir and Oseltamivir Carboxylate Pharmacokinetics in Obese Adults: Dose Modification for Weight Is Not Necessary

机译：肥胖成年人中的Oseltamivir和Oseltamivir羧酸盐药代动力学：无需调整剂量即可减轻体重

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Obesity is an independent risk factor for mortality in patients infected with pandemic influenza A virus (H1N1). Given the poor outcomes observed among adult obese patients with H1N1, the dosing of antiviral agents in this population has been questioned, and use of twice the standard oseltamivir dose has been suggested. However, studies evaluating the disposition of oseltamivir and oseltamivir carboxylate (the active metabolite) in the obese population are scant. We evaluated the single-dose and steady-state pharmacokinetics of oseltamivir (75 mg by mouth twice daily) in a cohort of 21 healthy adult volunteers with class III obesity (body mass index [BMI], ≥40 kg/m2). The median (minimum, maximum) age, weight, and BMI were 36 (19, 50) years, 122 (106, 159) kg, and 43.7 (40.0, 54.4) kg/m2, respectively. The population pharmacokinetic exposure profiles of oseltamivir carboxylate (the active metabolite) were comparable between class III obese subjects and nonobese adults (healthy and infected). Similar to previous pharmacokinetic analyses in nonobese subjects, the mean (percent covariance [CV]) area under the concentration-time curve for the dosing interval (AUC0–τ) was 2,621 ng·h/ml (17) for oseltamivir carboxylate. Body size was significantly (P < 0.05) associated with oseltamivir and oseltamivir carboxylate apparent clearance, but the correlation coefficient was poor (R2 ≤ 0.3). Creatinine clearance estimated by the Cockcroft-Gault method and lean body weight were also significantly (P < 0.05) but poorly (R2 = 0.17) correlated with oseltamivir carboxylate apparent clearance. Since the systemic exposure of oseltamivir carboxylate is not reduced in class III obese adults with standard doses, a dose increment of oseltamivir is likely to be unnecessary.
机译：肥胖是感染大流行性甲型流感病毒（H1N1）的患者死亡的独立危险因素。鉴于在成年肥胖的H1N1肥胖患者中观察到的不良结果，对该人群的抗病毒药物剂量提出了质疑，并建议使用两倍标准奥司他韦剂量。然而，评估肥胖人群中奥司他韦和奥司他韦羧酸盐（活性代谢物）的处置的研究很少。我们在21名III级肥胖（体重指数[BMI]，≥40kg / m 2）的健康成人志愿者中，评估了奥司他韦（口服两次，每天两次，口服75 mg）的单剂量和稳态药代动力学）。中位数（最小，最大）年龄，体重和BMI分别为36（19、50）kg，122（106、159）kg和43.7（40.0、54.4）kg / m 2 。在III类肥胖受试者和非肥胖成年人（健康者和受感染者）之间，奥司他韦羧酸盐（活性代谢物）的总体药代动力学暴露特征可比。与先前在非肥胖受试者中进行的药代动力学分析相似，剂量间隔（AUC0-τ）的浓度-时间曲线下的平均（百分数协方差[CV]）面积为奥司他韦羧酸盐的2,621 ng·h / ml（17）。与奥司他韦和奥司他韦羧酸盐表观清除率显着相关（P <0.05），但相关系数较差（R 2 ≤0.3）。用Cockcroft-Gault方法估计的肌酐清除率和瘦体重也与奥司他韦羧酸盐表观清除率相关（P <0.05），但差（R 2 = 0.17）差。由于在标准剂量的III类肥胖成年人中，奥司他韦羧酸盐的全身暴露没有减少，因此可能不需要增加奥司他韦的剂量。

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