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.
This is a preview of subscription content, log in via an institution to check access.
Similar content being viewed by others
References
Guideline on Laboratory Animals and Alternative Models in Biomedical Research. Karkishchenko NN, Grachev SV, eds. Moscow, 2010. Russian.
Bisadze NO. Diagnosis of depressive disorders in elderly patients in general medical practice. Klin. Gerontol. 2002;8(6):11-14. Russian.
Evaluation of Bioequivalence of Drugs. Methodological Guidelines. Moscow, 2008. P. 18-21. Russian.
Psychopharmacological and antiepileptic drugs allowed for use in the Russian Federation. Mosolov SN, ed. Moscow, 2004. Russian.
Goodman and Gilman’s the Pharmacological Basis of Therapeutics. New York, 2005.
Gus’kova TA. Preclinical toxicological studies of drugs as the basis for their safe use in the clinical practice. Klin. Issled. Lek. Sredstv Rossii. 2004;(3-4):8-15. Russian.
Karkishchenko NN. The Basics of Biomodeling. Moscow, 2004. Russian.
Kukes VG, Grachev SV, Sychev DA, Ramenskaya GV. Metabolism of drugs. The scientific basis of personalized medicine: a guide for physicians. Moscow, 2008. P. 240-253. Russian.
Kukes VG, Znamenskaya GV, Kuchumov RS, Astaev ON, Sychev DA, Rumyantsev AS. Genotyping of polymorphic “slow” alleles of cytochrome Р4502D6 for individualized assessment of amitriptyline pharmacokinetics in the Moscow population. Klin. Issled. Lek. Sredstv Rossii. 2002;(3-4):40-46. Russian.
Larina SN, Ignatiev IV, Tchebyschev NV, Ramenskaya CG, Paskhina OE. Optimization of modelling of drug biotransformation by CYP-system cytochromes. Biomeditsina. 2007;(6):48-56. Russian.
Manual for Preclinical Studies of New Pharmacological Substances. Part I, Mironov AN, ed. Moscow, 2012. Russian.
Mosolov SN. Clinical diagnosis and pharmacotherapy of depression in somatic practice. Ter. Arkh. 1999;71(10):70-76. Russian.
Clinical Pharmocogenetics. Kukes VG, Bochkov NP, eds. Moscow, 2007. Russian.
Manual on Experimental (Preclinical) Study of New Pharmacological Substances. Moscow, 200. P. 105-113. Russian.
Linden R, Antunes MV, Ziulkoski AL, Wingert M, Tonello P, Tzvetkov M, Souto AA. Determination of Amitriptyline and its Main Metabolites in Human Plasma Samples using HPLCDAD: Application to the Determination of Metabolic Ratios after Single Oral Dose of Amitriptyline. J. Braz. Chem. Soc. 2008;19(1):35-41.
Author information
Authors and Affiliations
Corresponding author
Additional information
Translated from Byulleten’ Eksperimental’noi Biologii i Meditsiny, Vol. 167, No. 3, pp. 330-337, March, 2019
Rights and permissions
About this article
Cite this article
Kondratenko, S.N., Savelyeva, M.I., Kukes, V.G. et al. Experimental and Clinical Pharmacokinetics of Fluoxetine and Amitriptyline: Comparative Analysis and Possible Methods of Extrapolation. Bull Exp Biol Med 167, 356–362 (2019). https://doi.org/10.1007/s10517-019-04526-9
Received:
Published:
Issue Date:
DOI: https://doi.org/10.1007/s10517-019-04526-9