Department of Pharmacy, St. Boniface General Hospital, and Department of Internal Medicine, the Faculty of Pharmacy, University of Manitoba, Winnipeg, Manitoba.
CMAJ. 2010 Mar 9;182(4):357-63. doi: 10.1503/cmaj.092127. Epub 2010 Feb 16.
Whether the enteric absorption of the neuraminidase inhibitor oseltamivir is impaired in critically ill patients is unknown. We documented the pharmacokinetic profile of oseltamivir in patients admitted to intensive care units (ICUs) with suspected or confirmed pandemic (H1N1) influenza.
We included 41 patients 18 years of age and older with suspected or confirmed pandemic (H1N1) influenza who were admitted for ventilatory support to nine ICUs in three cities in Canada and Spain. Using tandem mass spectrometry, we assessed plasma levels of oseltamivir free base and its active metabolite carboxylate at baseline (before gastric administration of the drug) and at 2, 4, 6, 9 and 12 hours after the fourth or later dose.
Among the 36 patients who did not require dialysis, the median concentration of oseltamivir free base was 10.4 (interquartile range [IQR] 4.8-14.9) microg/L; the median concentration of the carboxylate metabolite was 404 (IQR 257-900) microg/L. The volume of distribution of the carboxylate metabolite did not increase with increasing body weight (R2=0.00, p=0.87). The rate of elimination of oseltamivir carboxylate was modestly correlated with estimations of creatinine clearance (R2=0.27, p<0.001). Drug clearance in the five patients who required continuous renal replacement therapy was about one-sixth that in the 36 patients with relatively normal renal function.
Oseltamivir was well absorbed enterically in critically ill patients admitted to the ICU with suspected or confirmed pandemic (H1N1) influenza. The dosage of 75 mg twice daily achieved plasma levels that were comparable to those in ambulatory patients and were far in excess of concentrations required to maximally inhibit neuraminidase activity of the virus. Adjustment of the dosage in patients with renal dysfunction requiring continuous renal replacement therapy is appropriate; adjustment for obesity does not appear to be necessary.
神经氨酸酶抑制剂奥司他韦在危重症患者中的肠内吸收情况尚不清楚。我们记录了在加拿大和西班牙的三个城市的 9 个重症监护病房（ICU）中因疑似或确诊大流行性（H1N1）流感而住院的患者的奥司他韦药代动力学特征。
我们纳入了 41 例年龄在 18 岁及以上的因疑似或确诊大流行性（H1N1）流感而需要通气支持的患者，这些患者被收入加拿大和西班牙的三个城市的 9 个 ICU。采用串联质谱法，我们在基线（在给予药物前胃内给药）以及在第四剂或之后的 2、4、6、9 和 12 小时，评估奥司他韦游离碱及其活性代谢物羧酸的血浆水平。
在不需要透析的 36 例患者中，奥司他韦游离碱的中位浓度为 10.4（四分位距 [IQR] 4.8-14.9）μg/L；羧酸代谢物的中位浓度为 404（IQR 257-900）μg/L。羧酸代谢物的分布容积并未随体重增加而增加（R2=0.00，p=0.87）。奥司他韦羧酸的消除率与肌酐清除率的估计值呈适度相关（R2=0.27，p<0.001）。在需要连续肾脏替代治疗的 5 例患者中，药物清除率约为肾功能相对正常的 36 例患者的六分之一。
奥司他韦在因疑似或确诊大流行性（H1N1）流感而收入 ICU 的危重症患者中经肠内吸收良好。每日两次 75 mg 的剂量可达到与门诊患者相当的血浆水平，且远超过最大限度抑制病毒神经氨酸酶活性所需的浓度。对于需要连续肾脏替代治疗的肾功能障碍患者，需要调整剂量；对于肥胖患者，似乎不需要调整剂量。
