Время забора крови для проведения лекарственного мониторинга

ВРЕМЯ ЗАБОРА КРОВИ ДЛЯ ПРОВЕДЕНИЯ ЛЕКАРСТВЕННОГО МОНИТОРИНГА

Пробы крови для TDM должны быть взяты в фазе выведения лекарственного препарата, так как уровень концентрации в этой фазе надежнее воспроизводится, чем уровни концентрации в фазе всасывания или распределения. Для опре­деления фазы выведения необходимо знать вре­мя достижения Кmax, а также время резкого па­дения концентрации в результате перерас­пределения. Ошибки в определении времени забора крови (например, раньше времени до­стижения состояния равновесной концентра­ции или слишком рано после приема очеред­ной дозы препарата) могут вводить в заблужде­ние при выборе дозировки.

ЧАСТОТА ЛЕКАРСТВЕННОГО МОНИТОРИНГА

Частота мониторинга зависит от фармакокине-тических особенностей лекарственного сред­ства. Многие полагают, что TDM требует доста­точно частых заборов крови, что прежде всего связано с опытом применения лития. Это лекар­ственное средство в какой-то мере уникально тем, что уровень его концентрации определя­ется различными независимыми факторами. Отсюда следует, что уровень концентрации ли­тия в плазме крови зависит не только от дози­ровки и состояния почечной функции, но также и от состояния межтканевой жидкости, всасы­вания и выведения солей.

Для большинства лекарственных средств концентрация является производным дозировки, а также индивидуального уровня метаболизма и выведения, которые относительно устойчивы. Примерами опосредованного действия других переменных являются заболевания, которые влияют на органы, важные для метаболизма или выведения (например, печень или сердце), или другой лекарственный препарат, получаемый больным и способный стимулировать или по­давлять CYP ферменты, ответственные за био­трансформацию лекарственных средств.

Лекарственный мониторинг рекомендует­ся как стандартное исследование в тех случаях, когда препарат имеет относительно узкий те­рапевтический индекс и его клиренс в значи­тельной степени зависит от индивидуальных особенностей. Для большинства лекарственных препаратов такой контроль рекомендуется про­водить после того, как больной получает ста­бильную дозировку препарата на протяжении 5-7 периодов его полувыведения. Повторный контроль обычно проводится только по необ­ходимости. Причинами для повторного контро­ля могут стать изменения в эффективности ле­карственного средства или его переносимости, а также любые обстоятельства, которые могут повлиять на клиренс препарата (например, добавление второго лекарственного средства, которое может усиливать или подавлять мета­болизм первого препарата, или развитие бо­лезненного состояния, которое может отрица­тельно влиять на функцию левого желудочка сердца, печени или почек).

За исключением этих ситуаций TDM не требует повторения, так как полученный пока­затель определяется функциями метаболизма и выведения у конкретного больного, которые яв­ляются воспроизводимым и достаточно устой­чивым биологическим феноменом. Благодаря этому TDM используется для выявления нару­шений больным режима приема лекарств. Не­обходимо подчеркнуть, что для многих ле­карств подобный лабораторный анализ еще невозможен или данные об их фармакокинети-ческих свойствах недостаточны для интерпре­тации уровня концентрации лекарственного средства.

ЗАКЛЮЧЕНИЕ

В этой главе был сделан обзор важнейших фар-макокинетических принципов, имеющих отно­шение к большинству психотропных препа­ратов. Затем было показано различие между фармакодинамикой и фармакокинетикой. По­нимание фармакокинетики лекарственного сред­ства может способствовать безопасности и эффективности применения лекарственного препарата. Эти принципы как неотъемлемая часть планирования лечения и его контроля рассматриваются в следующих главах в связи с определенными видами лекарственной те­рапии.

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