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Pharmacology and Neuroscience

Dr. Paul R. Casner

Professor of Internal Medicine
Ph.D., 1975, New York Medical College
M.D., 1980, New York Medical College

Diabetes, hypertension and drug metabolism:

Clinical Pharmacology

Our research is focused on clinical pharmacology and has involved studies involving diabetes, hypertension and drug metabolism. In the field of diabetes our initial pharmacology studies demonstrated that combination therapy of oral sulfonylureas with insulin was beneficial in selected patients with type 2 diabetes. Patients with high C-peptide levels were often able to reduce insulin requirements by 50 percent. We have also done studies looking at comparing computerized pharmacokinetic dosing with that of dosing done empirically by physicians.

Our most recent research activity was in the area of pharmocogenetics. Drug metabolism is influenced by many factors. It has been known for some time that genetic alterations of drug metabolizing enzymes can have significant effects on drug disposition. Recent attention has been focused on genetic polymorphisms and the hepatic cytochrome P-450 enzyme system. Mutations in some of these cytochrome P-450 enzymes can lead to altered metabolism of drugs resulting in toxic concentrations of the drug, or in some situations where metabolism is accelerated, to very low levels of a particular drug. Distribution of these genetic polymorphisms vary depending on ethnic and racial characteristics. For example, the CYP2D6 enzyme has genetic mutations that result in poor metabolizers in 5 to 10 percent of Whites, while Asians have a rate of less than 1 percent. In contrast, studies have shown that up to 29 percent of Blacks are ultra rapid metabolizers. We have performed studies in Mexican-Americans to determine the incidence of genetic polymorphisms in the CYP2D6 enzyme system in this population. We found the rate of the poor metabolizer phenotype and genotype to be similar to non-Mexican-American Whites with a rate of about 6 percent.

Current research projects are examining the possible benefit of sulfonylureas in combination with meglitinides in improving glucose control in type 2 diabetics, a study analyzing the effects of sub-therapeutic INRs on patients treated with warfarin for mechanical heart valves and a study that analyzes patient compliance and preference for different warfarin dosing regimens.

In addition to the above investigations, we have been involved in numerous clinical trials of investigational drugs. The most recent of which was the newly approved Glp-analog, Exenatide for the treatment of type 2 diabetes.

Representative Publications

Casner, PR. The Effect of CYP2D6 Polymorphisms on Dextromethorphan Metatolism in Mexican Americans. J Clin Pharmacol 45:1230-5. 2005.

Casner, PR, Sandoval, E. Increased sensitivity to warfarin in elderly Hispanics. J Clin Pharmacol 42:145-150. 2002.

Casner, PR. Superwarfarin toxicity. Am J Therap 5:117-20. 1998.

Casner, PR. The inability to attain oral anticoagulation: warfarin-rifampin interaction revisited. South Med J. 89:1200-03. 1996.

Casner, PR, Reilly, R, Ho, H. A randomized controlled trial of computerized pharmacokinetic theophylline dosing versus empirical physician dosing. Clin Pharmacol Ther. 53:684-690. 1993.

Casner, PR, Guerra, LG. Purchasing prescription medication in Mexico without a prescription: the experience at the border. West J Med. 156:512-16. 1992.

Casner, PR, Dillon, KR. A comparison of the antihypertensive effectiveness of two triamterene/hydrochlorothiazide combinations: maxzide versus dyazide. J Clin Pharmacol. 30:715-719. 1990

Casner, PR. Insulin-glyburide combination therapy for non-insulin dependent diabetes mellitus: a long-term double-blind, placebo-controlled trial. Clin Pharmacol Ther. 44:594-603. 1988.

For further information contact Dr. Paul R. Casner