vedomostiregmedРегуляторные исследования и экспертиза лекарственных средствRegulatory Research and Medicine Evaluation3034-30623034-3453Federal State Budgetary Institution ‘Scientific Centre for Expert Evaluation of Medicinal Products’ of the Ministry of Health of the Russian Federation (FSBI ‘SCEEMP’)vedomostiregmed-21Research ArticleКЛИНИЧЕСКАЯ ФАРМАКОЛОГИЯCLINICAL PHARMACOLOGYНовые подходы к рациональной фармакотерапии невралгии тройничного нерва на основе методологии персонализированной медициныNew approaches to rationale pharmacotherapy of trigeminal neuralgia based on personalized medicine principlesАрхиповВ. В.ArkhipovV. V.archipov2005@rambler.ruСоколовА. В.SokolovA. V.noemail@neicon.ruРодинаТ. А.RodinaT. A.noemail@neicon.ruПоздняковД. Л.PozdnyakovD. L.noemail@neicon.ruСоковаЕ. А.SокоvаЕ. А.noemail@neicon.ruФедеральное государственное бюджетное учреждение «Научный центр экспертизы средств медицинского применения» Министерства здравоохранения Российской ФедерацииРоссияFederal State Budgetary Institution «Scientific Centre for Expert Evaluation of Medicinal Products» of the Ministry of Health of the Russian FederationRussian FederationГосударственное бюджетное учреждение здравоохранения «Городская клиническая больница № 23 им. Медсантруд» Департамента здравоохраненияРоссияState Institution of Health «Medsantrud City Clinical Hospital № 23» of Department of HealthRussian Federation201513022018011620Copyright © Архипов В.В., Соколов А.В., Родина Т.А., Поздняков Д.Л., Сокова Е.А., 20182018Архипов В.В., Соколов А.В., Родина Т.А., Поздняков Д.Л., Сокова Е.А.Arkhipov V.V., Sokolov A.V., Rodina T.A., Pozdnyakov D.L., Sокоvа Е.А.Данная работа распространяется под лицензией Creative Commons Attribution 4.0.This work is licensed under a Creative Commons Attribution 4.0 License.https://www.vedomostincesmp.ru/jour/article/view/21

Оптимизация фармакотерапии (подбор оптимальных дозировок лекарственных препаратов и интервалов дозирования) является одной из основных задач клинической фармакологии. Эта задача решается, в том числе, с помощью современных фармакокинетических подходов и реализуется путем использования терапевтического лекарственного мониторинга, заключающегося в подборе адекватной дозы лекарственных средств и интервала дозирования на основе знания точного значения концентраций препарата в определенные моменты времени. В первую очередь это актуально для препаратов с узким терапевтическим диапазоном. Авторами обосновывается целесообразность терапевтического лекарственного мониторинга при лечении обострения тригеминальной невралгии карбамазепином и оценивается практическая значимость разработки нового метода фенотипирования для повышения эффективности и безопасности фармакотерапии.

Optimization of pharmacotherapy (selection of optimal doses and dosing intervals) is a major objective of clinical pharmacology. This objective may be achieved, in part, by implementation of modern pharmacokinetic approaches and the use of therapeutic drug monitoring that consists in selection of an appropriate dose level and dosing interval based on information about drug concentrations at certain timepoints. This is particularly important for drugs with a narrow therapeutic range. The authors of the article advocate the usefulness of therapeutic drug monitoring in treating exacerbation of trigeminal neuralgia with carbamazepin and evaluate practical relevance of development of a new phenotyping method that could be used to increase pharmacotherapy efficiency and safety.

невралгия тройничного нерватерапевтический лекарственный мониторингантиконвульсантперсонализированная медицинарациональная фармакотерапияtrigeminal neuralgiatherapeutic drug monitoringanticonvulsantpersonalized medicinerational pharmacotherapyReferencesГусев Е.Н., Белоусов Ю.Б., Гехт А.Б., Бондарева И.Б., Соколов А.В., Тищенкова И.Ф. Лечение эпилепсии: Рациональное дозирование антиконвульсантов. СПб: Речь; 2000.Gusev EN, Belousov YuB, Geht AB, Bondareva IB, Sokolov AV, Tischenkova IF. Treatment of epilepsy: Rational dosing of anticonvulsants. St. Petersburg: Rech; 2000 (in Russian).Карлов В.А. Терапия нервных болезней. М.: Медицина; 2004.Karlov VA. Treatment of nervous diseases. Moscow: Meditsina; 2004 (in Russian).Кукес В.Г., Берри Д., ред. Терапевтический лекарственный мониторинг: инструмент персонализированной медицины. Методические рекомендации. М.: Международная ассоциация клинических фармакологов и фармацевтов; 2013.Kukes VG, Berry D, eds. Therapeutic drug monitoring: a tool for personalized medicine. Methodical recommendations. Moscow: Mezhdunarodnaya assotsiatsiya klinicheskih farmakologov i farmatsevtov; 2013 (in Russian).Мегдятов Р.С. Невралгия тройничного нерва. М.: Медицина; 1999.Megdyatov RS. Trigeminal neuralgia. Moscow: Meditsina; 1999 (in Russian).Кукес В.Г., ред. Персонализированная медицина: Клинико-фармакологические аспекты. М.: Международная ассоциация клинических фармакологов и фармацевтов; 2014.Kukes VG, ed. Personalized Medicine: Clinical and pharmacological aspects. Moscow: Mezhdunarodnaya assotsiatsiya klinicheskih farmakologov i farmatsevtov; 2014 (in Russian).Степанченко А.В., Гречко В.Е., Нейматов Э.М. Краниальные нервы в норме и при патологии. М.:МНПИ; 2001.Stepanchenko AV, Grechko VE, Neymatov EM. Cranial nerves in normal and pathological conditions. Moscow: MNPI; 2001 (in Russian).Кукес В.Г., ред. Справочник лекарственных средств, которые метаболизируются в организме человека. М.: Международная ассоциация клинических фармакологов и фармацевтов; 2013.Kukes VG, ed. Handbook of drugs that are metabolized in the human body. Moscow: Mezhdunarodnaya assotsiatsiya klinicheskih farmakologov i farmatsevtov; 2013 (in Russian).Холодов Л.Е., Яковлев В.П. Клиническая фармакокинетика. М.: Медицина; 1985.Holodov LE, Yakovlev VP. Clinical pharmacokinetics. Moscow: Meditsina; 1985 (in Russian).Pienimäki P., Hartikainen A.L., Arvela P., Partanen T., Herva R., Pelkonen O., Vähäkangas K. Carbamazepine and its metabolites in human perfused placenta and in maternal and cord blood. Epilepsia 1995; 36(3): 241-8.Pienimäki P, Hartikainen AL, Arvela P, Partanen T, Herva R, Pelkonen O, Vähäkangas K. Carbamazepine and its metabolites in human perfused placenta and in maternal and cord blood. Epilepsia 1995; 36(3): 241–8.Larry A. Applied Clinical Pharmacokinetics. McGraw-Hill; 2008.Larry A. Applied Clinical Pharmacokinetics. McGraw-Hill; 2008.Hung C.C., Chang W.L., Ho J.L., Tai J.J., Hsieh T.J., Huang H.C., Hsieh Y.W., Liou H.H. Association of polymorphisms in EPHX1, UGT2B7, ABCB1, ABCC2, SCN1A and SCN2A genes with carbamazepine therapy optimization. Pharmacogenomics 2012 Jan; 13(2): 159-69.Hung CC, Chang WL, Ho JL, Tai JJ, Hsieh TJ, Huang HC, Hsieh YW, Liou HH. Association of polymorphisms in EPHX1, UGT2B7, ABCB1, ABCC2, SCN1A and SCN2A genes with carbamazepine therapy optimization. Pharmacogenomics 2012 Jan; 13(2): 159–69.Serralheiro A., Alves G., Fortuna A., Rocha M., Falcão A. First HPLC-UV method for rapid and simultaneous quantification of phenobarbital, primidone, phenytoin, carbamazepine, carbamazepine-10,11-epoxide, 10,11-trans-dihydroxy-10,11-dihydrocarbamazepine, lamotrigine, oxcarbazepine and licarbazepine in human plasma. J Chromatogr B Analyt Technol Biomed Life Sci. 2013; Apr 15: 925.Serralheiro A, Alves G, Fortuna A, Rocha M, Falcão A. First HPLC-UV method for rapid and simultaneous quantification of phenobarbital, primidone, phenytoin, carbamazepine, carbamazepine-10,11-epoxide, 10,11-transdihydroxy-10,11- dihydrocarbamazepine, lamotrigine, oxcarbazepine and licarbazepine in human plasma. J Chromatogr B Analyt Technol Biomed Life Sci. 2013; Apr 15: 925.Sato J., Saitoh T., Notani K., Fukuda H., Kaneyama K., Segami N. Diagnostic significance of carbamazepine and trigger zones in trigeminal neuralgia. Oral Surg Oral Med Oral Pathol Oral Radiol Endod. 2004; PMID 14716252.Sato J, Saitoh T, Notani K, Fukuda H, Kaneyama K, Segami N. Diagnostic significance of carbamazepine and trigger zones in trigeminal neuralgia. Oral Surg Oral Med Oral Pathol Oral Radiol Endod. 2004; PMID 14716252.Guo-qiang Chen, Xiao-song Wang, Lin Wang, Jia-ping Zheng. Arterial compression of nerve is the primary cause of trigeminal neuralgia. Neurol Sci. 2014; 35(1): 61-66.Guo-qiang Chen, Xiao-song Wang, Lin Wang, Jia-ping Zheng. Arterial compression of nerve is the primary cause of trigeminal neuralgia. Neurol Sci. 2014; 35(1): 61–66.Кукес В.Г., Грачев С.В., Сычев Д.А. и др. Метаболизм лекарственных средств. Научные основы персонализированной медицины. М.: ГЭОТАР-Медиа; 2008.Kukes VG, Grachev SV, Sychev DA, et al. Metabolism of drugs. Scientific basis of personalized medicine. M .: GEOTAR-Media; 2008 (in Russian).USP Drug Information. Volume I: Drug Information for the Health Care Professional.24th ed. Bethesda: Greenwood Village Co; 2004.USP Drug Information. Volume I: Drug Information for the Health Care Professional.24th ed. Bethesda: Greenwood Village Co; 2004.Patsalos P.N., Berry D.J., Bourgeois B.F., Cloyd J.C., Glauser T.A., Johannessen S.I., Leppik I.E., Tomson T., Perucca E. Antiepileptic drugs-best practice guidelines for therapeutic drug monitoring: a position paper by the subcommision on therapeutic drug monitoring, ILAE commission on therapeutic strategies. Epilepsia 2008; (49): 1239-76.Patsalos PN, Berry DJ, Bourgeois BF, Cloyd JC, Glauser TA, Johannessen SI, Leppik IE, Tomson T, Perucca E. Antiepileptic drugs-best practice guidelines for therapeutic drug monitoring: a position paper by the subcommision on therapeutic drug monitoring, ILAE commission on therapeutic strategies. Epilepsia 2008; (49): 1239–76.Rambeck B., May T.W., Jürgens M.U., Blankenhorn V., Jürges U., Korn-Merker E., Sälke-Kellermann A. Comparison of phenytoin and carbamazepine serum concentrations measured by high-performance liquid chromatography, the standard TDx assay, the enzyme multiplied immunoassay technique, and a new patient-side immunoassay cartridge system. Ther Drug Monit. 1994; (16): 608-12.Rambeck B, May TW, Jürgens MU, Blankenhorn V, Jürges U, Korn-Merker E, Sälke- Kellermann A. Comparison of phenytoin and carbamazepine serum concentrations measured by high-performance liquid chromatography, the standard TDx assay, the enzyme multiplied immunoassay technique, and a new patient-side immunoassay cartridge system. Ther Drug Monit. 1994; (16): 608–12.Sanchez A., Garcia R., Abadin J.A., Duran J.A. Determination of free serum carbamazepine by protein precipitation with sulphosalicylic acid. Pharm Pharmacol Commun. 1999; (5): 435-438.Sánchez A, Garcia R, Abadin JA, Durán JA. Determination of free serum carbamazepine by protein precipitation with sulphosalicylic acid. Pharm Pharmacol Commun. 1999; (5): 435–438.Lanças F.M., Sozza M.A., Queiroz M.E. Simultaneous plasma lamotrigine analysis with carbamazepine, carbamazepine-10,11-epoxide, primidone, phenytoin, phenobarbital, and PEMA by micellar electrokinetic capillary chromatography (MECC). J Anal Toxicol 2003; (27): 304-308.20. Lanças FM, Sozza MA, Queiroz ME. Simultaneous plasma lamotrigine analysis with carbamazepine, carbamazepine-10,11-epoxide, primidone, phenytoin, phenobarbital, and PEMA by micellar electrokinetic capillary chromatography (MECC). J Anal Toxicol 2003; (27): 304–308.Romanyshyn L.A., Wichmann J.K., Kucharczyk N., Shumaker R.C., Ward D., Sofia R.D. Simultaneous determination of felbamate, primidone, Phenobarbital, carbamazepine, two carbamazepine metabolites, phenytoin and one phenytoin metabolite in human plasma by high-performance liquid chromatography. Ther Drug Monit. 1994; (16): 90-99.Romanyshyn LA, Wichmann JK, Kucharczyk N, Shumaker RC, Ward D, Sofia RD. Simultaneous determination of felbamate, primidone, Phenobarbital, carbamazepine, two carbamazepine metabolites, phenytoin and one phenytoin metabolite in human plasma by high-performance liquid chromatography. Ther Drug Monit. 1994; (16): 90–99.Bhatti M.M., Hanson G.D., Schultz L. Simultaneous determination of phenytoin, carbamazepine, and 10,11-carbamazepine epoxide in human serum by high-performance liquid chromatography with ultra-violet detection. J карбамазепин-10,11-эпоксида, что существенно повышает эффективность и безопасность проведения рациональной фармакотерапии с применением препарата карбамазепина, в частности при НТН.Bhatti MM, Hanson GD, Schultz L. Simultaneous determination of phenytoin, carbamazepine, and 10,11-carbamazepine epoxide in human serum by high-performance liquid chromatography with ultra-violet detection. J Pharm Biomed Anal. 1998; (16): 233–1240.Queiroz M.E., Silva S.M., Carvalho D., Lancas F.M. Determination of lamotrigine simultaneously with carbamazepine, carbamazepine epoxide, phenytoin, Phenobarbital, and primidone in human plasma by SPME-GC-TSD. J Chromatogr Sci. 2002; 40: 219-23.Queiroz ME, Silva SM, Carvalho D, Lancas FM. Determination of lamotrigine simultaneously with carbamazepine, carbamazepine epoxide, phenytoin, Phenobarbital, and primidone in human plasma by SPME-GC-TSD. J Chromatogr Sci. 2002; 40: 219–23.Yoshida T., Imai K., Motohashi S., Hamano S., Sato M. Simultaneous determination of zonisamide, carbamazepine and carbamazepine-10,11-epoxide in infant serum by high-performance liquid chromatography. J Pharm Biomed Anal. 2006; (41): 1386-90.Yoshida T, Imai K, Motohashi S, Hamano S, Sato M. Simultaneous determination of zonisamide, carbamazepine and carbamazepine-10,11-epoxide in infant serum by high- performance liquid chromatography. J Pharm Biomed Anal. 2006; (41): 1386–90.Oh E., Ban E., Woo JS., Kim CK. Analysis of carbamazepine and its active metabolite, carbamazepine-10,11-epoxide, in human plasma using high-performance liquid chromatography. Anal Bioanal Chem. 2006; (386): 1931-36.Oh E, Ban E, Woo JS, Kim CK. Analysis of carbamazepine and its active metabolite, carbamazepine-10,11-epoxide, in human plasma using high-performance liquid chromatography. Anal Bioanal Chem. 2006; (386): 1931–36.Leite C.E., Petersen G.O., Lunardelli A., Thiesen F.V. A high-performance liquid chromatography method for the determination of carbamazepine and car-bamazepine-10,11-epoxide and its comparison with chemiluminescent immunoassay. Clin Chem Lab Med. 2009; (47): 458-63.Leite CE, Petersen GO, Lunardelli A, Thiesen FV. A high-performance liquid chromatography method for the determination of carbamazepine and carbamazepine-10,11-epoxide and its comparison with chemiluminescent immunoassay. Clin Chem Lab Med. 2009; (47): 458–63.Breton H., Cociglio M., Bressolle F., Peyriere H., Blayac J.P., Hillaire-Buys D. Liquid chromatography-electrospray mass spectrometry determination of carbamazepine, oxcarbazepine and eight of their metabolites in human plasma. J Chromatogr B Analyt Technol Biomed Life Sci. 2005; (828): 80-90.Breton H, Cociglio M, Bressolle F, Peyriere H, Blayac JP, Hillaire-Buys D. Liquid chromatography-electrospray mass spectrometry determination of carbamazepine, oxcarbazepine and eight of their metabolites in human plasma. J Chromatogr B Analyt Technol Biomed Life Sci. 2005; (828): 80–90.Subramanian M., Birnbaum A.K., Remmel R.P. High-speed simultaneous determination of nine antiepileptic drugs using liquid chromatography-mass spectrometry. Ther Drug Monit. 2008; (30): 347-56.Subramanian M, Birnbaum AK, Remmel RP. High-speed simultaneous determination of nine antiepileptic drugs using liquid chromatography-mass spectrometry. Ther Drug Monit. 2008; (30): 347–56.Vuckovic D., de Lannoy I., Gien B., et al. Yang Y., Musteata F.M., Shirey R., Sidisky L., Pawliszyn J. In vivo solid-phase microextration for single rodent pharmacokinetics studies of carbamazepine and carbamazepine-10, 11-epoxide in mice.Vuckovic D, de Lannoy I, Gien B, et alYang Y, Musteata FM, Shirey R, Sidisky L, Pawliszyn J. In vivo solid-phase microextration for single rodent pharmacokinetics studies of carbamazepine and carbamazepine-10, 11-epoxide in mice. J Chromatogr A 2010; (1218): 3367–75.

The authors declare that there are no conflicts of interest present.