Evan Kharasch, MD, PhD
Russell D. and Mary B. Shelden Professor of Anesthesiology
Director, Division of Clinical and Translational Research Department of Anesthesiology
Professor of Biochemistry and Molecular Biophysics
Dr. Kharasch’s laboratory is devoted to clinical and bidirectional translational research in pharmacology, with a focus on perioperative and critical care. The overall goal is to understand the role of hepatic and extra-hepatic drug metabolism and drug transport in the pharmacokinetics, pharmacodynamics, pharmacogenetics, toxicity, and variability in patient response to anesthetic and nonanesthetic drugs. These are directed towards optimizing drug disposition, drug safety, clinical effectiveness, patient satisfaction, and pharmacoeconomics. A second major goal is proteomic urine biomarkers development for perioperative renal function, renal disease and nephrotoxicity. Research encompasses both laboratory investigations of drug metabolism and transport using human tissues and enzymes, and clinical volunteer and patient studies to confirm laboratory findings.
Major program areas include:
- Mechanisms of interindividual variability in opioid disposition and clinical response, specifically with respect to pharmacogenetics, drug interactions, stereochemistry, age and gender effects. In vitro models of opioid metabolism use human liver, intestinal and renal tissue to identify responsible drug metabolizing enzymes, and in vivo studies deliberately manipulate enzyme activities and assess their pharmacokinetic and pharmacodynamic consequences. Also compares opioids for therapeutic induces. Major opioids of interest include methadone and buprenorphine. The overall goal is to improve the use of opioids to treat postoperative pain, cancer pain and drug abuse.
- Role of drug transporters in drug disposition. Addresses the role of intestinal, hepatic and renal influx and efflux drug transporters in drug oral absorption, bioavailability, and elimination, and the role of blood brain barrier transporters in CNS drug access and drug pharmacodynamics. Also addresses drug interactions and pharmacogenetics.
- Influence of HIV/AIDS drug interactions on in vitro and clinical drug metabolism and transport.
- Development of novel noninvasive methods for assessing hepatic and intestinal cytochrome P450 activity in humans in vivo. The goal is to detect interindividual variability in drug metabolizing activity, enzyme induction and inhibition caused by other drugs, and predict the disposition of drugs with narrow therapeutic indices in order to optimize therapy.
- Influence of morbid obesity on perioperative drug disposition.
- Pain and analgesia in sickle cell disease.
- Development of noninvasive biomarkers for acute and chronic renal disease.
- Mechanism(s) of volatile anesthetic toxicity and identification of clinical strategies for their prevention. Focuses on hepatic and renal toxicities, and as a corollary, because volatile anesthetics are halogenated hydrocarbons (industrial solvents and environmental contaminants), the extension of these investigations to haloalkyl toxicity in general, and the appropriateness of animal models to human toxicity assessment. Includes determining the specific cytochrome P450 isoforms which metabolize volatile anesthetics in human liver and kidney, role of intrarenal metabolism, and the evaluation of breakdown products from volatile anesthetic degradation in anesthesia circuits.
- Alternative routes of drug administration for control of chronic and breakthrough cancer pain, specifically, nasal opioid administration.