INDUCTIVE EFFECTS OF NELFINAVIR AND RITONAVIR (I)

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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. Anti-HIV protease inhibitors (PRIs) like ritonavir and nelfinavir have the propensity to produce clinically-relevant inductive and inhibitory drug interactions. To quantify inductive drug interactions of the PRIs, we wish to determine the extent to which nelfinavir or ritonavir induce the activity of the following cytochrome P450 enzymes (CYP): 1A2, 2C9, 2D6, 3A and P-glycoprotein (P-gp). We will accomplish this by administering drugs which will measure the in vivo activities of these enzymes and transporter, both before and after induction with nelfinavir or ritonavir. To aid in correlating these results to results obtained in vitro we will compare the in vivo induction of CYPs and P-gp by the PRIs to that obtained with rifampin, a well known inducer of CYP enzymes and P-gp.