Rahul Deshmukh, PhD

Dr. Rahul Deshmukh, Assistant Professor of Pharmaceutical Sciences, joined the College in 2011. Dr. Deshmukh received his BS in Pharmacy from the University of Mumbai in 1996, followed by a Master in Pharmacy in 1998 from the same university. He went on to obtain a PhD in Pharmaceutical Sciences in 2003, from University of Maryland. Following postdoctoral studies in the School of Pharmacy at West Virginia University, he pursued drug discovery and development research in the pharmaceutical industry for 6 years. In industry, his research was focused on understanding and improving the Absorption, Distribution, Metabolism and Excretion (ADME) properties of preclinical drug candidates.

In his current role, Dr. Deshmukh is responsible for developing the Pharmaceutics Course Curriculum for the PharmD program. In addition, he is also responsible for developing the Basic Pharmacokinetics and Pharmacodynamics course curriculum. His research interests include understanding mechanisms of CYP mediated drug-drug interactions (DDIs); pharmacokinetic modeling of CYP-dependent DDIs; invitro-invivo correlations of drug clearance and drug interaction and the effect of CYP polymorphisms on drug clearance.

Curriculum Vitae

Courses

• Basic Pharmacokinetics and Pharmacodynamics
• Pharmaceutics II: Dosage Forms
• Pharmaceutics III: Compounding and Calculations

Research

In addition to efficacy, factors critical for development of a successful drug candidate include good drug metabolism and pharmacokinetic (DMPK) properties along with minimal toxicity. Generally, inferior DMPK properties result in poor absorption, high clearance and have been attributed to the failure of oral drugs during the clinical development. In addition, potential of drug interactions or their inadequate understanding can complicate successful drug development. The prediction of human pharmacokinetics and metabolism of drugs is critical to advance the right compounds into clinical settings. Though, use of in vitro data to extrapolate in vivo has aided the effort allowing for prediction of pharmacokinetic parameters, with our current understanding, the translation to a clinical outcome is far from accurate.

I plan to build a research program that is aimed at improving our understanding and prediction of DMPK properties of drugs using in silico and in vitro tools. Specifically my research will be focused on understanding mechanisms of CYP mediated drug-drug interactions (DDIs); pharmacokinetic modeling of CYP-dependent DDIs; in vitro-in vivo correlations of drug clearance and drug interaction and the effect of CYP polymorphisms on drug clearance.

Publications

1. Deshmukh R, Blomme E. (2009) A dog is not a rat: importance of understanding species differences in drug absorption, distribution, metabolism and excretion (ADME). Vet J. 179(1):8-9.
2. Tu Y, Deshmukh R, Sivaneri M, Szklarz GD. (2008) The Application of Molecular Modeling for Prediction of Substrate Specificity in Cytochrome P450 1A2 Mutants. Drug Metab Dispos. 36(11):2371-80
3. Hom K, Deshmukh R, Furci L, Wilks A. (2007) NMR assignments of cd-HO, a 24 kDa heme oxygenase from Corynebacterium diphtheria. Biomol. NMR Assignments. (1):55-56
4. Deshmukh R, Huang HW, Zeng Y, Furci LM, Moenne-Loccoz P, Rivera M, Wilks A. Heme Oxidation and Regioselectivity in a Chimeric Protein of the α-selective Neisserriae meningitides Heme Oxygenase (nm-HO): Replacement of the Distal Helix of nm-HO with that of the δ-selective Pseudomonas aeruginosa (pa-HO). Biochemistry. 44(42):13713-23.
5. Zheng Y, Deshmukh R*, Rivera M, Wilks A. (2004). Mixed Regioselectivity in the Arg-177 Mutants of Corynebacterium diphtheriae Heme Oxygenase is a Consequence of a Dynamic Equilibrium between Two Alternate Heme Seatings. Biochemistry. 43(18):5222-38 (* Shared First Authorship)
6. Caignan GA, Deshmukh R, Zeng Y, Huang HW, Moenne-Loccoz P, Bunce RA, Eastman MA, Wilks A, Rivera M. (2003). Magnetic resonance studies on Fe^III - hydroxide as a model to mimic the hydroperoxide intermediate of heme oxygenase reaction in Pseudomonas aeruginosa heme oxygenase. J Am Chem Soc. 125(39):11842-52.
7. Friedman J, Lad L, Deshmukh R, Li H, Wilks A, Poulos T. (2003). Crystal Structures of the NO- and CO-Bound Heme Oxygenase from Neisseriae meningitidis: Implications for O₂ Activation. J Biol Chem. 278(36):34654-9.
8. Caignan GA, Deshmukh R, Wilks A, Zeng Y, Huang HW, Moenne-Loccoz P, Bunce RA, Eastman MA, Rivera M. (2002). Oxidation of heme to beta- and delta-biliverdin by Pseudomonas aeruginosa heme oxygenase as a consequence of an unusual seating of the heme. J Am Chem Soc. 124(50):14879-92.
9. Ratliff M, Zhu W, Deshmukh R, Wilks A, Stojiljkovic I. (2001). Homologues of Neisseria heme oxygenase in gram-negative bacteria: degradation of heme by the product of the pigA gene of Pseudomonas aeruginosa. J Bacteriol. 183:6394-403.
10. Deshmukh R, Tu Y, Ericksen SS, Gannett PM, Szklarz GD. Orientation of phenacetin and acetaminophen within the active-site of human cytochromes P450 1A1 and 1A2 - a NMR and homology modeling study. (expected submission – Summer 2011)