Hage K, Bühl K, Fischer C, Knebel N G
Dr. Margarete Fischer-Bosch-Institut für Klinische Pharmakologie, Stuttgart, Germany.
Eur J Clin Pharmacol. 1995;48(1):51-5. doi: 10.1007/BF00202172.
Data on the absolute bioavailability of flecainide are controversial. We have investigated whether differences in metabolic clearances and/or the absorption profile might be responsible for the variability in its absolute bioavailability. Six subjects with a wide range of flecainide metabolic clearances (85-407 ml.min-1) simultaneously received the drug by the IV and oral routes; the oral dose was labelled with deuterium. Besides estimation of absolute bioavailability, this design permitted assessment of metabolic clearance after IV and oral administration, and absorption could be assessed from the urinary excretion of labelled and unlabelled drug and metabolites. The absolute bioavailability of flecainide ranged from 79.9 to 101.1% (mean 93.6%). The absorption was 86.1 to 101.3% (mean 93.2%). The data indicate that the variable bioavailability of flecainide is due both to metabolism and absorption. The study highlights the potential of stable isotope technique in the investigation of such issues.
关于氟卡尼绝对生物利用度的数据存在争议。我们研究了代谢清除率和/或吸收情况的差异是否可能是其绝对生物利用度变异性的原因。六名氟卡尼代谢清除率范围较广（85 - 407 ml·min⁻¹）的受试者同时通过静脉注射和口服途径接受该药物；口服剂量用氘标记。除了估计绝对生物利用度外，该设计还允许评估静脉注射和口服给药后的代谢清除率，并且可以从标记和未标记药物及代谢物的尿排泄情况评估吸收情况。氟卡尼的绝对生物利用度范围为79.9%至101.1%（平均93.6%）。吸收情况为86.1%至101.3%（平均93.2%）。数据表明，氟卡尼生物利用度的变异性是由代谢和吸收共同导致的。该研究突出了稳定同位素技术在研究此类问题方面的潜力。
