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Pharmacokinetics and toxicokinetics; drugs of abuse; in vitro-in vivo metabolism;
pharmacodynamics
Research Activities
Past and current research activities are broadly based and fall
into the general areas of pharmacokinetics, biopharmaceutics,
toxicokinetics and pharmacodynamics. The purpose of such experimentation
(in either animals or humans) is to quantitatively describe the
disposition of a drug or toxicant in the body. These studies involve
the measurement of drug/toxicant and metabolite concentrations
in biological fluids and tissues in order to describe the various
processes that such compounds undergo in the body (i.e., absorption,
distribution, metabolism and excretion). Such data usually allow
the development of a biological and mathematical model which may
be used to help explain what is happening to a substance and/or
predict what would happen if the system (i.e., the body) were
to undergo a change. An additional important aspect of these
experiments is to quantitatively measure responses to the drug/toxicant
and relate that behavior to the dose-concentration-time profiles.
Research activities in recent years have emphasized the pharmacokinetics
and toxicology of drugs of abuse (e.g., methamphetamine, cocaine),
their interaction (e.g., cocaine-ethanol interaction) and response
concentration relationships. Current research involves the examination
of the absorption and pharmacokinetics of active components of
botanicals (e.g., green tea). The in vivo work is being done in
the Yucatan minipig. Sensitive and specific analytical methods
need to be developed for all such studies (e.g., enantiomer-selective
assays for the enantiomers of methamphetamine and its metabolite,
amphetamine). Additional activities include: simulations of enzyme
kinetic data in order design more efficient experimental methods;
theoretical and practical applications of physiologically-based
pharmacokinetic models; prevention of absorption of drugs/toxicants
and heavy metals following an acute oral overdose; the oretical
aspects of analysis of hair for studying drugs of abuse; quantitative
relationship between in vitro drug metabolism in liver slices
and in vivo parameters (in collaboration with Dr. Brendel).
Publications (Query PubMed for this investigator)
T. Kakkar, Y. Pak and M. Mayersohn: Evaluation of a Minimal
Experimental Design for Determination of Enzyme Kinetic Parameters
and Inhibition Mechanism, J. Pharmacol. Exp. Ther., 293:861-869,
2000.
V. Sinha, K. Brendel and M. Mayersohn: A Simple Isolated
Perfused rat Liver Apparatus: Characterization and Measurement
of Extraction Ratios of Selected Drugs, Life Sci., 66:1795-1804,
2000.
T. Kakkar, H. Boxenbaum and M. Mayersohn: Estimation of
Ki in a Competitive Enzyme-Inhibition Model: comparisons Among
Three Methods of Data Analysis, Drug Metab. Dispos., 27:756-762,
1999.
J.S. Valdez, D.K. Martin and M. Mayersohn: Sensitive and
Selective Gas Chromatographic Methods for the Quantitation of
Camphor, Menthol and Methyl Salicylate from Human Plasma, J. Chromatogr.
B, 729:163-171, 1999.
H.J. Pieniaszek, Jr., M. Mayersohn, M.P. Adams, R.J. Reinhart
and J.S. Barett: Moricizine Bioavailability via Simultaneous,
Dual, Stable Isotope Administration: Bioequivalence Implications,
J. Clin Pharmacol.,39:817-825, 1999.
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