Influence of pharmacotherapy on function of biotransformation of xenobiotics liver in patients with neuropsychiatric disorders

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Abstract

BACKGROUND: The mechanisms of drug interactions of psychotropic drugs are associated with the processes of drug biotransformation by enzymes of microsomal oxidation of cytochrome P-450 in the liver. Various drugs can increase or decrease the activity of enzymes of the cytochrome P450-dependent system.

AIM: To evaluate the effect of pharmacotherapy with psychotropic drugs: alprazolam, bromazepam, lithium carbonate on the metabolic rate of the model substrate antipyrine in saliva in patients with neuropsychiatric disorders; the effect of the enzyme-inducing activity of the original anticonvulsant 1-[(3-chlorophenyl)(phenyl)methyl]urea on the pharmacokinetic parameters of antipyrine in healthy volunteers.

MATERIALS AND METHODS: 34 male patients were divided into three groups according to the nosological forms of diseases according to ICD-10: Group 1 — heading F43.23 and F43.25; 2 — F06.61; 3 — F41.2. Patients in the group 1 were prescribed alprazolam, in the 2 — bromazepam, in the 3 — lithium carbonate, for a course of 21 days. The comparison group consisted of 10 healthy volunteers. The original anticonvulsant was prescribed to the volunteers. Determination of the pharmacokinetics of antipyrine parameters as a test witness of the processes of elimination from the body was carried out in saliva before and after the end of therapy at a dose of 10 mg/kg once.

RESULTS: Alprazolam administration by patients of group 1 at a dose of 0.5–1.5 mg/day for 21 days did not significantly affect the pharmacokinetic parameters of antipyrine: T1/2, Clt, AUC. Alprazolam did not change the elimination of antipyrine from the saliva of patients. In patients of the group2, who received bromazepam at a dose of 6–12 mg / day,
a background decrease in T1/2, an increase in Clt, a decrease in AUC due to concomitant therapy were noted. Comparison of the pharmacokinetic parameters of antipyrine under the influence of bromazepam with background values not reveal significant differences. Therapy with lithium carbonate at a dose of 500–1000 mg/day in patients of the group 3 did not change the parameters of antipyrine elimination. The obtained data indicate that the drugs do not affect the activity of liver microsomal oxidation in patients. The study of the effect of 1-[(3-chlorophenyl)(phenyl)methyl]urea on the pharmacokinetic parameters of antipyrine in volunteers revealed a diametrically opposite result: a significant decrease in T1/2 by 2 times, an increase in Clt and a decrease in AUC, which indicates accelerated elimination of antipyrine from the saliva of the subjects and indicates the induction of liver microsomal oxidation.

CONCLUSIONS: Pharmacotherapy using the studied psychotropic drugs in patients is not associated with the induction or inhibition of liver enzymes, which indicates the absence of drug pharmacokinetic interference. The original anticonvulsant 1-[(3-chlorophenyl)(phenyl)methyl]urea stimulated the induction of liver microsomal oxidation in volunteers.

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About the authors

Tamara V. Shushpanova

Tomsk National Research Medical Center of the Russian Academy of Sciences; Federal Scientific and Clinical Center for Medical Rehabilitation and Balneology of the Federal Medical and Biological Agency of Russia

Email: shush59@mail.ru
ORCID iD: 0000-0002-9455-0358
SPIN-code: 9158-9235
Scopus Author ID: 6506299310
ResearcherId: J-2817-2017

MD, Cand. Sci. (Medicine)

Russian Federation, Tomsk; Tomsk

Irina E. Kupriyanova

Tomsk National Research Medical Center of the Russian Academy of Sciences

Email: irinakupr@rambler.ru
ORCID iD: 0000-0003-2495-7811
SPIN-code: 1617-6349

MD, Dr. Sci. (Medicine), Professor

Russian Federation, Tomsk

Nikolay Aleksandrovich Bokhan

Tomsk National Research Medical Center of the Russian Academy of Sciences; Siberian State Medical University

Email: mental@tnimc.ru
ORCID iD: 0000-0002-1052-855X
SPIN-code: 2419-1263
Scopus Author ID: 6506895310.

MD, Dr. Sci. (Medicine), Professor, Academician of Russian Academy of Sciences

Russian Federation, Tomsk; Tomsk

Tatiana V. Kazennykh

Tomsk National Research Medical Center of the Russian Academy of Sciences; Siberian State Medical University

Author for correspondence.
Email: tvk151@yandex.ru
ORCID iD: 0000-0002-6253-4644
SPIN-code: 6956-3031

MD, Dr. Sci. (Medicine)

Russian Federation, Tomsk; Tomsk

Tatiana P. Novozheeva

Tomsk National Research Medical Center of the Russian Academy of Sciences;т Siberian State Medical University

Email: ntp53@mail.ru
ORCID iD: 0000-0003-4218-6723

Dr. Sci. (Biology)

Russian Federation, Tomsk; Tomsk

Evgeny D. Schastnyy

Tomsk National Research Medical Center of the Russian Academy of Sciences

Email: evgeny.schastnyy@gmail.com
ORCID iD: 0000-0003-2148-297X
SPIN-code: 6482-2439

MD, Dr. Sci. (Medicine), Professor

Russian Federation, Tomsk

Valentina B. Nikitina

Tomsk National Research Medical Center of the Russian Academy of Sciences

Email: vbnikitina@yandex.ru
ORCID iD: 0000-0002-1644-770X
SPIN-code: 3687-7727

Dr. Sci. (Medicine)

Russian Federation, Tomsk

Mikhail M. Aksenov

Tomsk National Research Medical Center of the Russian Academy of Sciences

Email: max1957@mail.ru
ORCID iD: 0000-0002-8949-6596
SPIN-code: 7599-1801

MD, Dr. Sci. (Medicine), Professor

Russian Federation, Tomsk

Olga E. Perchatkina

Tomsk National Research Medical Center of the Russian Academy of Sciences

Email: poa@antline.ru
ORCID iD: 0000-0001-5538-1304
SPIN-code: 6299-0859

MD, Cand. Sci. (Medicine)

Russian Federation, Tomsk

Elena V. Gutkevich

Tomsk National Research Medical Center of the Russian Academy of Sciences

Email: gutkevich.elena@rambler.ru
ORCID iD: 0000-0001-7416-7784
SPIN-code: 6427-9007

Dr. Sci. (Medicine)

Russian Federation, Tomsk

Olga V. Shushpanova

Mental Health Research Center

Email: sertraline@list.ru
ORCID iD: 0000-0003-3484-3447
SPIN-code: 8979-9700

 канд. мед. наук

Russian Federation, Moscow

Irina N. Smirnova

Federal Scientific and Clinical Center for Medical Rehabilitation and Balneology of the Federal Medical and Biological Agency of Russia

Email: irin-smirnova@yandex.ru
ORCID iD: 0000-0002-9010-2419
SPIN-code: 1873-9302

Dr. Sci. (Medicine)

Russian Federation, Tomsk

Alexei А. Zaitsev

Federal Scientific and Clinical Center for Medical Rehabilitation and Balneology of the Federal Medical and Biological Agency of Russia

Email: alzay2010@yandex.ru
ORCID iD: 0000-0003-2601-1739

MD, Cand. Sci. (Medicine)

Russian Federation, Tomsk

Natalia P. Garganeeva

Tomsk National Research Medical Center of the Russian Academy of Sciences; Siberian State Medical University

Email: garganeeva@gmail.com
SPIN-code: 5449-1169

MD, Dr. Sci. (Medicine)

Russian Federation, Tomsk; Tomsk

Mikhail V. Belousov

Siberian State Medical University

Email: mvb63@mail.ru
ORCID iD: 0000-0002-2153-7945
SPIN-code: 8185-8117

Dr. Sci. (Pharmacy)

Russian Federation, Tomsk

Artem M. Guryev

Siberian State Medical University

Email: titan-m@mail.ru
ORCID iD: 0000-0002-1120-4979
SPIN-code: 3731-4439

Dr. Sci. (Pharmacy)

Russian Federation, Tomsk

Olga A. Vasileva

Siberian State Medical University

Email: vasiljeva-24@yandex.ru
ORCID iD: 0000-0002-2882-4533
SPIN-code: 9665-5714

MD, Cand. Sci. (Medicine)

Russian Federation, Tomsk

Vladimir V. Udut

Tomsk National Research Medical Center of the Russian Academy of Sciences

Email: udutv@mail.ru
ORCID iD: 0000-0002-3829-7132
SPIN-code: 8645-9815

MD, Dr. Sci. (Medicine), Professor, Сorresponding member of the Russian Academy of Sciences

Russian Federation, Tomsk

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