Bulletin of Experimental Biology and Medicine
Vol.167, Issue3, P. 356-362
Аннотация:
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. © 2019, Springer Science+Business Media, LLC, part of Springer Nature.
Ключевые слова:
amitriptyline; extrapolation; fluoxetine; nortriptyline; pharmacokinetics
amitriptyline; cytochrome P450 1A; cytochrome P450 1A2; cytochrome P450 2C; cytochrome P450 2C19; cytochrome P450 2C9; cytochrome P450 2D6; cytochrome P450 3A4; fluoxetine; nicotinamide; nortriptyline; amitriptyline; fluoxetine; nortriptyline; adult; animal experiment; area under the curve; Article; controlled study; demethylation; drug absorption; drug bioavailability; drug blood level; drug capsule; drug clearance; drug distribution; drug retention; elimination half-life; experimental study; female; human; human experiment; male; maximum concentration; mean residence time; mongrel dog; nonhuman; normal human; pharmacokinetic parameters; plasma concentration-time curve; single drug dose; tablet; time to maximum plasma concentration; trend study; volume of distribution; animal; bioavailability; blood; comparative study; dog; oral drug administration; Administration, Oral; Amitriptyline; Animals; Biological Availability; Dogs; Female; Fluoxetine; Humans; Male; Nortriptyline
Kondratenko S. N. Svetlana Nikolaevna 1964-
Savelyeva M. I.
Kukes V. G. Vladimir Grigoryevich 1934-
Shikh E. V. Evgeniya Valeryevna 1962-
Gneushev E. T.
Кондратенко С. Н. Светлана Николаевна 1964-
Савельева М. И.
Кукес В. Г. Владимир Григорьевич 1934-
Ших Е. В. Евгения Валерьевна 1962-
Гнеушев Е. Т.
Experimental and Clinical Pharmacokinetics of Fluoxetine and Amitriptyline: Comparative Analysis and Possible Methods of Extrapolation
Текст визуальный непосредственный
Bulletin of Experimental Biology and Medicine
Springer New York Consultants Bureau
Vol.167, Issue3 P. 356-362
2019
Статья
amitriptyline extrapolation fluoxetine nortriptyline pharmacokinetics
amitriptyline cytochrome P450 1A cytochrome P450 1A2 cytochrome P450 2C cytochrome P450 2C19 cytochrome P450 2C9 cytochrome P450 2D6 cytochrome P450 3A4 fluoxetine nicotinamide nortriptyline amitriptyline fluoxetine nortriptyline adult animal experiment area under the curve Article controlled study demethylation drug absorption drug bioavailability drug blood level drug capsule drug clearance drug distribution drug retention elimination half-life experimental study female human human experiment male maximum concentration mean residence time mongrel dog nonhuman normal human pharmacokinetic parameters plasma concentration-time curve single drug dose tablet time to maximum plasma concentration trend study volume of distribution animal bioavailability blood comparative study dog oral drug administration Administration, Oral Amitriptyline Animals Biological Availability Dogs Female Fluoxetine Humans Male Nortriptyline
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. © 2019, Springer Science+Business Media, LLC, part of Springer Nature.