比较药物动力学和生物利用度的tapentadol口服后立即,prolonged-release配方。
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Gohler K, Brett M, Smit JW, Rengelshausen J, Terlinden R
比较药物动力学和生物利用度的tapentadol口服后立即,prolonged-release配方。
51 Int中国新药杂志。2013年4月;(4):338 - 48。doi: 10.5414 / CP201722。
- PubMed ID
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23357834 (在PubMed]
- 文摘
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目的:探讨口服生物利用度和药物动力学的管理tapentadol立即释放(IR)与tapentadol长期释放(PR)。方法:三个随机、非盲、交叉研究是在受试者在禁食条件下进行的。研究1和2的绝对生物利用度和药物动力学决定口服tapentadol IR 86毫克和tapentadol公关86毫克,分别相对于34毫克剂量静脉注射(IV) tapentadol。研究3确定tapentadol公关86毫克的相对生物利用度和tapentadol IR 86毫克。药代动力学参数计算使用dose-adjusted non-compartmental分析和相对生物利用度,最大浓度的对数转换方差分析模型血清浓度时间曲线下面积(Cmax)和(AUC0-t和AUC)。不良事件(AEs)、生命体征、12导心电图(ecg)和实验室参数评估。结果:绝对生物利用度约为32%(95%可信区间(CI), 29.4 - 34.8%;n = 24) tapentadol IR 86毫克和32%(95%可信区间,28.0 - 35.9%;n = 18) tapentadol公关86毫克。基于AUC, tapentadol公关与tapentadol IR的相对生物利用度为96%(90%可信区间,87.8 - 104.4%; n = 16). Following IV administration, tapentadol had an elimination half-life of about 4 hours; in Studies 1 and 2, respectively, mean tapentadol volumes of distribution were 540 and 471 l, and mean clearance was 1,531 and 1,603 ml/min. Compared to tapentadol IR 86 mg, the prolonged-release characteristics of tapentadol PR 86 mg were evident with a lower Cmax (22.5 ng/ml vs. 64.2 ng/ml), a longer time to Cmax (5.0 h vs. 1.5 h), a higher half-value duration (HVD: 12.5 h vs. 3.6 h), and a longer mean residence time (MRT: 10.6 h vs. 6.0 h). The most common AEs reported were dizziness, headache, fatigue, nausea, somnolence, and dry mouth; most AEs were mild. No clinically relevant changes in vital signs, ECG parameters, or laboratory values were observed. CONCLUSIONS: Absolute bioavailability for both tapentadol IR and tapentadol PR was ~ 32% under fasted conditions. Extent of exposure (AUC) for tapentadol PR was very similar to tapentadol IR, whereas Cmax was lower and HVD/MRT longer for the prolonged-release formulation. Overall, the pharmacokinetic characteristics of tapentadol PR enable a twice-daily dosing regimen to be used; such a regimen is expected to improve patient compliance during chronic use.
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- 药物