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Mephentermine and phentermine, substances prohibited in sports by the World Anti-Doping Agency, were found for the first time in urine specimens following the administration of a therapeutic medication, oxethazaine. In a recent sporting event, a urine specimen donor who tested positive for mephentermine and phentermine claimed consumption of Mucaine((R)) for treating stomach pain was the reason for testing positive. Five volunteers were administrated oxethazaine (a topical anesthetic found in the multi-ingredient medication Mucaine and its generic equivalent, Stoin, both of which are available in Taiwan), mephentermine, and phentermine. Excretion profiles of mephentermine and phentermine following the administration of these drugs were found to be similar. However, the mephentermine/phentermine ratios found in urine specimens collected at different time points following the administration of oxethazine and mephentermine were found to be characteristically different.

Two N,N-dimethylphentermine (N,N-dimethyl-2-amino-2-methyl-3-phenylpropane) substrates differing in deuterium substitution have been used to determine the intermolecular and intramolecular isotope effects associated with the cytochrome P-450-dependent N-demethylation of this substrate. No intermolecular isotope effect was observed in Vmax or Vmax/Km when the reaction rates for this substrate were compared to those for the substrate in which both N-methyl groups contained deuterium. In contrast, identical isotope effects of 1.6 to 2.0 were observed in both Vmax and Vmax/Km when this reaction was studied with a substrate in which only one of the two N-methyl groups was substituted with deuterium. Furthermore, both the intermolecular and intramolecular isotope effects were independent of the cytochrome P-450/NADPH-cytochrome P-450 reductase mole ratio. From these data, it is concluded that: 1) the carbon-hydrogen bond cleavage step does not contribute significantly to Vmax; 2) the contribution of the carbon-hydrogen bond cleavage step to Vmax is not detectably increased through changes in the cytochrome P-450/NADPH-cytochrome P-450 reductase mole ratio; 3) the N-methyl groups are free to exchange at the enzyme active site. The basis for these conclusions is the proposal of a new kinetic model for interpretation of intramolecular isotope effects which shows that intramolecular isotope effects are not necessarily equal to intrinsic isotope effects and, in fact, may be much smaller.