Experimental and Clinical Pharmacokinetics of Fluoxetine and Amitriptyline: Comparative Analysis and Possible Methods of Extrapolation
- Authors: Kondratenko S.N.1, Savelyeva M.I.2, Kukes V.G.1, Shikh E.V.1, Gneushev E.T.3
-
Affiliations:
- 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
- Department of Clinical Pharmacology and Therapy, Russian Medical Academy for Continuous Professional Education, Ministry of Health of the Russian Federation
- Laboratory of Drug Toxicology, National Medical Research Center of Cardiology, Ministry of Health of the Russian Federation
- Issue: Vol 167, No 3 (2019)
- Pages: 356-362
- Section: Pharmacology and Toxicology
- URL: https://journals.rcsi.science/0007-4888/article/view/241698
- DOI: https://doi.org/10.1007/s10517-019-04526-9
- ID: 241698
Cite item
Abstract
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.
About the authors
S. N. Kondratenko
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
Author for correspondence.
Email: snko@mail.ru
Russian Federation, Moskva
M. I. Savelyeva
Department of Clinical Pharmacology and Therapy, Russian Medical Academy for Continuous Professional Education, Ministry of Health of the Russian Federation
Email: snko@mail.ru
Russian Federation, Moscow
V. G. Kukes
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
Email: snko@mail.ru
Russian Federation, Moskva
E. V. Shikh
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
Email: snko@mail.ru
Russian Federation, Moskva
E. T. Gneushev
Laboratory of Drug Toxicology, National Medical Research Center of Cardiology, Ministry of Health of the Russian Federation
Email: snko@mail.ru
Russian Federation, Moscow