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北美黑人和白人中口服普萘洛尔的稳态相对生物利用度及药代动力学

Steady state relative bioavailability and pharmacokinetics of oral propranolol in black and white North Americans.

作者信息

Sharoky M, Perkal M, Turner R, Lesko L J

机构信息

Pharmakinetics Laboratories, Inc., Baltimore, Maryland.

出版信息

Biopharm Drug Dispos. 1988 Sep-Oct;9(5):447-56. doi: 10.1002/bod.2510090503.

Abstract

The steady state bioavailability and pharmacokinetics of propranolol over two consecutive dosing intervals were investigated in 18 black and 10 white normal volunteers following the administration of 20 mg of a test and reference oral dosage form, respectively, every 6 h. There were no differences (p greater than 0.05) between dosage forms in the mean (n = 28) area under the plasma concentration-time curve (AUC), maximum plasma concentration (Cmax) or time to Cmax (tmax) for propranolol or its active metabolite, 4-hydroxypropranolol. However, as a group blacks had lower plasma concentrations of propranolol during the second dosing interval (AUC-2 and Cmax-2, respectively) were significantly (p less than 0.05) lower in blacks, but there were no ethnic differences (p greater than 0.05) in tmax. The mean AUC and Cmax for the 4-hydroxylated metabolite during both dosing intervals were significantly (p less than 0.05) lower in blacks. Mean oral clearances of propranolol, assuming complete absorption, (range: 42.1-54.5 ml min-1 kg-1) were similar (p greater than 0.05) in each racial group. There were no substantial changes in heart rate or blood pressure in blacks or whites following propranolol administration. These data suggest that for oral propranolol, blacks have different absorption and disposition characteristics than whites.

摘要

在18名黑人及10名白人正常志愿者中,分别给予20mg的试验性和参比口服剂型,每6小时一次,连续两个给药间隔,研究普萘洛尔的稳态生物利用度和药代动力学。对于普萘洛尔及其活性代谢物4 - 羟基普萘洛尔,两种剂型在血浆浓度 - 时间曲线下的平均(n = 28)面积(AUC)、最大血浆浓度(Cmax)或达峰时间(tmax)方面无差异(p>0.05)。然而,作为一个群体,黑人在第二个给药间隔期间普萘洛尔的血浆浓度较低(分别为AUC - 2和Cmax - 2),黑人的这些值显著较低(p<0.05),但tmax无种族差异(p>0.05)。在两个给药间隔期间,黑人中4 - 羟基代谢物的平均AUC和Cmax显著较低(p<0.05)。假设完全吸收,普萘洛尔的平均口服清除率(范围:42.1 - 54.5 ml min⁻¹ kg⁻¹)在每个种族组中相似(p>0.05)。给予普萘洛尔后,黑人或白人的心率和血压没有实质性变化。这些数据表明,对于口服普萘洛尔,黑人与白人具有不同的吸收和处置特征。

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