Gene D. Morse

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OBJECTIVE Methylphenidate (MPH), the most commonly prescribed drug for attention-deficit/hyperactivity disorder (ADHD), has a short half-life, which necessitates multiple daily doses. The need for multiple doses produces problems with medication administration during school and after-school hours, and therefore with compliance. Previous long-acting(More)
Non-nucleoside reverse transcriptase inhibitors (NNRTIs) are a diverse group of compounds that induce allosteric changes in the human immunodeficiency virus type 1 (HIV-1) reverse transcriptase, thus rendering the enzyme incapable of converting viral RNA to DNA. Unlike nucleoside analogue inhibitors of reverse transcriptase, NNRTIs do not require sequential(More)
In AIDS Clinical Trials Group protocols 384, A5095, and A5097s, we characterized relationships between 22 polymorphisms in CYP2B6, ABCB1, and CYP3A5; plasma efavirenz exposure; and/or treatment responses. A stepwise logistic regression procedure selected polymorphisms associated with reduced drug clearance adjusted for body mass index and the composite(More)
BACKGROUND Efavirenz and nelfinavir are metabolized by cytochrome P-450 (CYP) 2B6 and CYP2C19, respectively, with some involvement by CYP3A. Nelfinavir is a substrate for P-glycoprotein, which is encoded by MDR1. The present study examined associations between genetic variants and long-term responses to treatment. METHODS Adult AIDS Clinical Trials Group(More)
Opioid addiction and HIV disease frequently co-occur. Adverse drug interactions have been reported between methadone and some HIV medications, but less is known about interactions between buprenorphine, an opioid partial agonist used to treat opioid dependence, and HIV therapeutics. This study examined drug interactions between buprenorphine and the(More)
BACKGROUND It is unclear whether therapy for human immunodeficiency virus type 1 (HIV-1) should be initiated with a four-drug or two sequential three-drug regimens. METHODS In this multicenter trial we compared initial therapy involving four-drug regimens containing efavirenz and nelfinavir in combination with either didanosine and stavudine or zidovudine(More)
STUDY OBJECTIVE To determine if milk thistle (silymarin) alters the pharmacokinetics of indinavir. DESIGN Sequential crossover trial. SETTING General clinical research center. SUBJECTS Ten healthy subjects. INTERVENTION Indinavir 800 mg 3 times/day was given for four doses on days 1 and 2. Silymarin 160 mg 3 times/day was given on days 3-15. On day(More)
OBJECTIVE Delavirdine is a non-nucleoside reverse transcriptase inhibitor used in combination regimens for the treatment of HIV-1 infection. Our objective was to characterise the population pharmacokinetics of delavirdine in HIV-infected patients who participated in the adult AIDS Clinical Trials Group (ACTG) 260 and 261 studies. METHODS ACTG 261 was a(More)
The understanding of the cytochrome P450 3A SNP in antiretroviral therapy is important, because it is highly inducible, extremely polymorphic and metabolizes many of the drugs that are key components of highly active antiretroviral therapy regimens. This enzyme is prolific and promiscuous towards drug and xenobiotic substrate selection and it is also(More)
OBJECTIVES Prior candidate gene studies have associated CYP2B6 516G→T [rs3745274] and 983T→C [rs28399499] with increased plasma efavirenz exposure. We sought to identify novel variants associated with efavirenz pharmacokinetics. MATERIALS AND METHODS Antiretroviral therapy-naive AIDS Clinical Trials Group studies A5202, A5095, and ACTG 384 included plasma(More)