Kondratenko S N, Savelyeva M I, Kukes V G, Shikh E V, Gneushev E T
Department of Clinical Pharmacology and Propaedeutics of Internal Diseases, I. M. Sechenov First Moscow State Medical University (Sechenov University), Ministry of Health of the Russian Federation, Moskva, Russia.
Department of Clinical Pharmacology and Therapy, Russian Medical Academy for Continuous Professional Education, Ministry of Health of the Russian Federation, Moscow, Russia.
Bull Exp Biol Med. 2019 Jul;167(3):356-362. doi: 10.1007/s10517-019-04526-9. Epub 2019 Jul 26.
The pharmacokinetics of two fluoxetine capsulated dosage forms and two amitriptyline tablet forms after a single oral intake was studied in dogs and healthy volunteers. High significant correlations were detected between plasma concentrations of fluoxetine (r=0.96, p<0.00001, n=11) and amitriptyline (r=0.78, p<0.0224, n=8) in dogs and volunteers. A correlation of medium strength (though insignificant) was detected between nortriptyline concentrations in the plasma of dogs and volunteers (r=0.69, p<0.199, n=5). The bioavailability parameters of the test drugs in dogs and volunteers did not differ. Similar trends of fluoxetine and amitriptyline pharmacokinetic parameters were revealed in volunteers and animals. Methods for extrapolation of experimental pharmacokinetics parameters of fluoxetine and amitriptyline obtained on dogs for humans are proposed and validated.
在犬类和健康志愿者中研究了两种氟西汀胶囊剂型和两种阿米替林片剂单次口服后的药代动力学。在犬类和志愿者中，氟西汀血浆浓度之间（r = 0.96，p < 0.00001，n = 11）以及阿米替林血浆浓度之间（r = 0.78，p < 0.0224，n = 8）检测到高度显著相关性。在犬类和志愿者血浆中去甲替林浓度之间检测到中等强度相关性（虽不显著）（r = 0.69，p < 0.199，n = 5）。受试药物在犬类和志愿者中的生物利用度参数无差异。在志愿者和动物中揭示了氟西汀和阿米替林药代动力学参数的相似趋势。提出并验证了将在犬类上获得的氟西汀和阿米替林实验药代动力学参数外推至人类的方法。
