METHAMPHETAMINE DISPOSTION KINETICS IN ANIMALS

Amphetamine and numerous derivatives, including methamphetamine, have been
used therapeutically for many years. These agents are known to have abuse
potential which was clearly evidenced in the United states (in the 1950s
and 1960s) and in several countries in Asia. A far more frightening specter
has no appeared on the horizon, "ice", which is a smokeable form of
methamphetamine. Currently, the use of "ice" in Hawaii is as wide-spread
as that of crack cocaine. Recent literature has referred to this new threat
as, "the drug plague of the 1990s"0. The incidence of its use and reports
of toxicity and death have increased dramatically in recent years. The overall aim and long-term objective of this proposal is to obtain
information necessary to develop and test rational modes of therapy to
treat toxicity due to methamphetamine and its congeners. In order to do
disposition kinetics of the drug need to be examined. The rat will serve
as the animal model. The acute disposition kinetics will be determined as
a function of dose and route (intravenous, oral and smoking). Disposition
following chronic dosing will also be determined by selected routes. The
pharmacokinetic interaction of methamphetamine with other selected drugs
of abuse (known to be coingested by abusers) will be examined: ethanol,
cocaine, marijuana. The potential interaction with other compounds will
also be examined (e.g., PCP, nicotine, caffeine). From the above
information strategies for the treatment of toxicity will emerge and will
be tested. A physiological pharmacokinetic model will be developed in order
to attempt to relate temporal patterns of disposition to other species
including humans. Finally, fetal exposure to methamphetamine will be
determined. Future work will examine the disposition of selected congeners of
methamphetamine for which there is little or no information; extend the
work here to other species including humans and pursue development of a
pharmacodynamic-pharmacokinetic model.