Clinical pharmacology is often defined simply as the study of the effects of drugs in humans. Investigators in this department focus on many aspects of clinical pharmacology, including pharmacokinetics and pharmacodynamics, kinetic-dynamic modeling, pathways of drug metabolism (especially cytochrome-mediated biotransformation and glucuronidation), special population factors (including development and aging, gender, infection with HIV, drug-drug interactions), prediction and scaling from animal models, analytic method development for the study of drugs in body tissue and fluids and mathematical models describing the behavior of drugs in man. The laboratories in this area use advances in molecular pharmacology and other basic science techniques to further the understanding of how drugs work in man. We have access to the clinical departments and staff of the New England Medical Center, including its federally supported General Clinical Research Center. In addition, there is a dedicated unit for the study of human volunteers within our department. The members of the Division of Clinical Pharmacology have decades of experience in clinical research and drug development, as well as in the care of patients with complex medication regimens. One of our major interests involve drugs affecting the central nervous system. Members of the department with particular interest in clinical pharmacology include:

Dr. Dominic A. Ciraulo is interested in the pharmacology of substance abuse. In the early stages, his research centered on the use of antidepressants in patients with alcoholism. Along with his co-investigators, he has published a number of articles on the pharmacokinetics and clinical utility of antidepressents in patients with alcoholism and depression. At the VA outpatient clinic, he is also directing trials of novel antianxiety agents in clinical populations.

Dr. David J. Greenblatt is studying the pharmacokinetics of a number of drug classes, including benzodiazepine-derivative drugs used to treat AIDS, azole antifungal agents, and antidepressants. He is evaluating how the pharmacokinetic properties of the drugs influence their clinical actions, as well as how factors such as old age, gender, and drug interactions influence drug disposition and effects.

Jerold S. Harmatz is involved in managing the inpatient and outpatient clinical drug trials within the division of Clinical Pharmacology in the department. He is responsible for the statistical evaluation of all data obtained from such trials.

Dr. Richard I. Shader's major focus in clinical pharmacology has been on adverse reactions, drug interactions, pharmacokinetics, aging, as well as clinical trials with antianxiety agents, hypnotics, antidepressants, and antipsychotic agents

Dr. Paul R. Skolnik initiated and directs the HIV Research Laboratory in the Division of Geographic Medicine and Infectious Diseases at New England Medical Center. He is the Director of the Immunovirology Core Laboratory for the NIH-funded Center for AIDS Research (CFAR) at Lifespan and Tufts University School of Medicine. He is also the Associate Program Director for the NIH-sponsored General Clinical Research Center at Tufts-New England Medical Center. In addition, Dr. Skolnik runs clinical protocols for HIV-seropositive persons at NEMC and provides the basic virology support for these and other trials, including in vitro measures of antiretroviral efficacy, antiretroviral resistance, phenotypic analysis, and viral load measurements.

Dr. Theoharis C. Theoharides has developed in vivo and in vitro models for neuroimmunoendocrine syndromes and are studying neurohormonal activation of mast cells and drugs which inhibit this effect. In particular, they have measured mast cell mediators in urine of interstitial cystitis patients which may be used to easier diagnose this syndrome. A clinical study is now in progress at the NEMC Clinical Research Center to investigate the ability of a mast cell secretion inhibitor to reduce interstitial cystitis symptoms.