Pharmacokinetics of oral methamphetamine and effects of repeated daily dosing in humans.
The pharmacokinetics of orally administered S-(+)-methamphetamine-d3 were investigated in human male volunteers before and after a 13-day course of a slow release form of S-methamphetamine hydrochloride. A one-compartment pharmacokinetic model incorporating a lag time fits the data best. The average elimination half-life was 10.1 hr (range of 6.4-15.1 hr). There were no statistically significant differences in pharmacokinetic parameters when a low dose (0.125 mg/kg) was given before and after the 13-day oral regimen. When a higher challenge dose (0.250 mg/kg) was used, the maximum plasma concentration of methamphetamine-d3 was slightly but significantly greater when the test dose was given at the end of the oral dosing period than when it was given at the beginning. Although minor differences in pharmacokinetics occur after subchronic treatment with low doses of methamphetamine, their result would be to increase plasma concentration of the drug. Therefore, development of pharmacodynamic tolerance to methamphetamine could not be explained on the grounds of a change in pharmacokinetics.
Cook
C E
CE
Research Triangle Institute, Research Triangle Park, NC 27709-2194.
Jeffcoat
A R
AR
Sadler
B M
BM
Hill
J M
JM
Voyksner
R D
RD
Pugh
D E
DE
White
W R
WR
Perez-Reyes
M
M
D000284:Administration, Oral; D000328:Adult; D006801:Humans; D007668:Kidney / Q000378:metabolism; D008297:Male; D008694:Methamphetamine / Q000008:administration & dosage / Q000493:pharmacokinetics*
D008694:Methamphetamine