OBSTETRICS FETAL PHARMACOLOGY RESEARCH NETWORK UNIT PITTSBURGH COCKTAIL

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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.