OBSTETRICS FETAL PHARMACOLOGY RESEARCH NETWORK UNIT PITTSBURGH COCKTAIL

这个子项目是利用由NIH/NCRR资助的中心拨款提供的资源的许多研究子项目之一。子项目和调查员(PI)可能从另一个NIH来源获得了主要资金，因此可能会出现在其他CRISE条目中。列出的机构是针对中心的，而不一定是针对调查员的机构。这项研究的目的是测试在药物代谢酶的诱导和怀孕对这些酶的诱导的影响方面，狒狒模型作为人类的替代物。这是一项简单的研究，旨在测试含有咖啡因、氟比洛芬、外消旋体/美苯妥因、去氢异喹、氯唑沙宗和氨苯松酮(用于非怀孕妇女)的传统6种药物匹兹堡鸡尾酒与由咖啡因、氟比洛芬、奥美拉唑、美托洛尔、对乙酰氨基酚和红霉素组成的怀孕鸡尾酒的对比。之所以选择这些特定的药物，是因为它们将允许评估P450酶系统的几个元素，包括CYP1A2、CYP2C9、CYP2C19、CYP2D6、CYP2E1和CYP3A。虽然这两种鸡尾酒的设计是为了研究酶对相同酶的诱导作用，但怀孕鸡尾酒实际上从未进行过测试。预计这只狒狒将被证明是一个很好的模特，而两杯匹兹堡鸡尾酒将被证明是等同的。随后，随着可能获得FDA批准的新药问世，狒狒将成为测试怀孕对这些药物新陈代谢的影响，特别是通过这些P450酶的新陈代谢机制的优秀模型。这项研究的潜力是巨大的，因为它可能表明狒狒是研究怀孕期间药代动力学和药效学纵向变化的优秀模型。

This subproject is one of many research subprojects utilizing the resources provided by a Center grant funded by NIH/NCRR. The subproject and investigator (PI) may have received primary funding from another NIH source, and thus could be represented in other CRISP entries. The institution listed is for the Center, which is not necessarily the institution for the investigator. The purpose of this study is to test the baboon model as a surrogate for the human as regards induction of drug metabolizing enzymes and the effects of pregnancy upon changes in induction of these enzymes. This is a simple study designed to test the conventional 6-drug Pittsburg cocktail containing caffeine, flurbiprofen, racemic/mephenytoin, debrisoquine, chlorozoxazone, and dapsone (as used in non-pregnant women) against a cocktail that is designed to be used in pregnancy that consists of caffeine, flurbiprofen, omeprazole, metoprolol, acetaminophen, and erythromycin. These specific drugs are chosen as they will allow evaluation of several elements of the P450 enzyme system to include CYP1A2, CYP2C9, CYP2C19, CYP2D6, CYP2E1, and CYP3A. While the two cocktails are designed to look at enzyme induction of the same exact enzymes, the pregnancy cocktail has never actually been tested. It is anticipated that the baboon will prove to be an excellent model and that the 2 Pittsburg cocktails will be equivalent. Subsequently, as new drugs become available that will likely receive FDA approval the baboon will serve as an excellent model for testing the effects of pregnancy upon metabolism of these drugs and specifically the mechanism of metabolism via these P450 enzymes. The potential of this study is substantial inasmuch as it is likely to show the baboon to be an excellent model for study of changes in pharmacokinetics and pharmacodynamics longitudinally across pregnancy.