Influence of activated charcoal on the disposition kinetics of methamphetamine enantiomers in the rat following intravenous dosing

Methamphetamine (MAP) is a central nervous system stimulant that is widely abused by populations of several countries. There is no specific antidote for the treatment of an overdose. Activated charcoal administered orally has been used to enhance the systemic elimination of certain toxic substances via 'gastrointestinal dialysis'. The results of in vitro studies have shown that MAP can be rapidly adsorbed from solution by activated charcoal. We have evaluated the effect of a single oral dose of activated charcoal on the disposition kinetics of MAP following a short iv infusion. Male Sprague- Dawley rats were given an oral dose of activated charcoal (Actidose-aqua, 1 g/kg) 10 min before a short iv infusion of racemic MAP; whereas the control group was given an equivalent volume of water. Enantiomers of MAP and metabolites in serum and urine were analyzed by an enantiomer-specific method which employed HPLC and detection of a fluorescent derivative. There were no differences in any of the disposition parameters between the two groups. Within each group, the clearance (CL(S)) of l-MAP was greater than that of d- MAP. However, there were no differences in the steady-state volume of distribution (V(SS)). The CL(S) (mL/(min kg)) and V(SS) (L/kg) values for l- and d-MAP in the control group were (mean ± SD): 85.8 ± 20.4, 48.7 ± 17.9, 2.64 ± 1.16, and 2.90 ± 1.36, respectively. The corresponding values in the charcoal-pretreated group were (mean ± SD): 57.4 ± 23.4, 51.1 ± 20.7, 2.79 ± 1.32, and 2.98 ± 1.47. These results suggest that oral activated charcoal does not enhance the elimination of MAP from the body.