Oseltamivir and Oseltamivir Carboxylate Pharmacokinetics in Obese Adults: Dose Modification for Weight Is Not Necessary
Oseltamivir and Oseltamivir Carboxylate Pharmacokinetics in Obese Adults: Dose Modification for Weight Is Not Necessary
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DOI：
10.1128/aac.00422-11
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发表时间：
2011-12-01
影响因子：
4.9
通讯作者：
Lodise, Thomas P., Jr.
中科院分区：
文献类型：
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作者：
Pai, Manjunath P.;Lodise, Thomas P., Jr.
肥胖是甲型H1N1流感病毒感染患者死亡的独立危险因素。鉴于在成年肥胖 H1N1 流感患者中观察到的不良预后，该人群中抗病毒药物的剂量受到质疑，并建议使用两倍于标准奥司他韦剂量。然而，评估奥司他韦和奥司他韦羧酸盐（活性代谢物）在肥胖人群中的分布的研究很少。我们在 21 名患有 III 级肥胖（体重指数 [BMI]，≥ 40 kg/m(2)）的健康成年志愿者中评估了奥司他韦（75 mg，每日两次）的单剂量和稳态药代动力学。中位（最小、最大）年龄、体重和BMI分别为36（19、50）岁、122（106、159）kg和43.7（40.0、54.4）kg/m（2）。羧酸奥司他韦（活性代谢物）的群体药代动力学暴露曲线在 III 级肥胖受试者和非肥胖成人（健康和感染）之间具有可比性。与之前在非肥胖受试者中进行的药代动力学分析类似，给药间隔的浓度-时间曲线下面积 (AUC(0-tau)) 的平均值（协方差百分比 [CV]）为 2,621 ng。 h/ml (17) 为奥司他韦羧酸盐。体型大小与奥司他韦和羧酸奥司他韦的表观清除率显着相关（P < 0.05），但相关系数较差（R-2
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/m(2)). 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/m(2), 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 (AUC(0-tau)) 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 (R-2