Gregory A Reed, PhD
Ph.D., Wayne State University, 1981
Drug disposition in humans, drug-drug and drug-diet interactions, pharmacokinetics, inter- and intra-individual variability in pharmacokinetics, bioanalytical chemistry
The biological effects of drugs and other chemicals are controlled in large part by their pharmacokinetics. This balance of the absorption, distribution, metabolism, and excretion of the drug or chemical determines, for a given dose or exposure, how much active chemical reaches its site of action and how long it persists at that site. The physicochemical and biochemical properties of the drug or chemical are critical factors in defining its pharmacokinetics. Inter-individual variability, however, may occur as a result of polymorphisms in the genes coding for the membrane transporters and enzymes involved in the disposition of a drug or chemical. In addition, both inter- and intra-individual variability in pharmacokinetics of a drug or chemical may occur due to the effects of other drugs, dietary components or supplements, and other "environmental" exposures. Defining the pharmacokinetics of a drug is critical for establishing appropriate doses and dosing intervals, and understanding the potential for drug-drug interactions, drug-diet interactions, and other environmental factors altering pharmacokinetics are essential for anticipating and preventing significant variability in pharmacokinetics.
We develop and validate liquid chromatography-tandem mass spectrometry methods (LC-MS/MS) for the analysis of specific drugs and their metabolites from plasma and other biological samples, and then apply those methods to samples from pre-clinical and clinical drug studies. The data then are used to calculate parameters defining the pharmacokinetics of that drug. We have developed and applied these methods to provide critical data for fifteen cancer therapy clinical trials, two clinical trials of proposed cancer chemopreventive agents, four smoking cessation studies, and three non-cancer clinical trials. In addition, we have studied the effects of two commonly used botanical/herbal supplements for their possible effects on the metabolism and kinetics of prescription and over-the-counter drugs in healthy human subjects. Currently, we are performing the analytical and pharmacokinetics components of four cancer therapeutics clinical trials, for a study of a novel therapy for Alzheimer's disease, and for two large-scale smoking cessation studies.
Womble, P.R., Van Veldhuizen, P.J., Nisbet, A.A., Reed, G.A., Thrasher, J.B., and Holzbeierlein, J.M. A phase II clinical trial of neoadjuvant ketoconazole and docetaxel chemotherapy prior to radical prostatectomy in high-risk patients. J. Urology, 186:882-887, 2011. PMID:21791342
Gor, P., Alnouti, Y., and Reed, G.A. Buspirone, fexofenadine, and omeprazole: Quantification of probe drugs and their metabolites. J Pharm Biomed Anal 55: 1127-1135, 2011. PMID: 21546194; PMCID: PMC3100389
Flynn, C.A., Alnouti, Y., and Reed, G.A. Quantitation of the transporter substrate fexofenadine in cell lysates by LC-MS/MS. Rapid Commun Mass Spec 25: 2361-2366, 2011. PMID: 21766379; PMCID: PMC4076838
Okuyemi, K.S., Faseru, B., Reed, G.A., Cox, L.S., Bronars, C.A., Opole, I., Whembolua, G.-L., Mayo, M.S., Ahluwalia, J.S., and Benowitz, N.L. Effects of menthol on the pharmacokinetics of bupropion among African American smokers. Nicotine Tobacco Res, 14(6):688-93, 2012. PMID: 22318754; PMCID: PMC3356293
Rigler, S.K., Wiggins, S., Mahnken, J., and Reed, G.A. Extent of variability in fentanyl plasma levels during steady-state transdermal delivery in older nursing home residents. J. Amer. Geriatr. Soc. 60: 1986-1988, 2012. PMID: 23057458
Minden, M.D., Hogge, D.E., Weir, S.J., Kasper, J., Webster, D.A., Patton, L., Jitkova, Y., Hurren, R., Gronda, M., Goard, C.A., Rajewski, L.G., Haslam, J.L., Heppert, K.E., Schorno, K., Chang, H., Brandwein, J.M., Gupta, V.,Schuh, A.C., Trudel, S., Yee, K.W., Reed, G.A., Schimmer, A.D. Oral ciclopirox olamine displays biological activity in a phase I study in patients with advanced hematologic malignancies. Amer J Hematol 89:363-368, 2013. doi: 10.1002/ajh.23640. PMID: 24273151
Hellings JA, Reed G, Cain SE, Zhou X, Barth FX, Aman MG, Palaguachi GI, Mikhnev D, Teng R, Andridge R, Logan M, Butler MG, Han JC. Loxapine Add-on for Adolescents and Adults with Autism Spectrum Disorders and Irritability. J Child Adolesc Psychopharmacol. 25:150-159, 2015. doi: 10.1089/cap.2014.0003. PMID: 25782098, PMCID: PMC4442591.
Williamson SK, Johnson GA, Maulhardt HA, Moore KM, McMeekin DS, Schulz TK, Reed GA, Roby KF, Mackay CB, Smith HJ, et al. A phase I study of intraperitoneal nanoparticulate paclitaxel (Nanotax®) in patients with peritoneal malignancies. Cancer Chemother Pharmacol. 75: 1075-1087, 2015. PMID: 25898813, PMCID: PMC4506131.