(+)‐Methamphetamine (METH) pharmacokinetics in timed‐pregnant rats during early‐ and late‐stage pregnancy

Abstract

The purpose of these studies was to better understand the potential pharmacological impact of METH use through pharmacokinetic studies of METH and (+)‐amphetamine (AMP, a pharmacologically active metabolite) in female rats during early‐ and late‐stage pregnancy. Rats received an i.v. dose of METH (1 mg/kg) on either gestational day 7 (GD7), just prior to organogenesis, or on GD21, 1–2 days before parturition. METH and AMP concentrations in serum and urine were quantitated by LC‐MS/MS. As gestation progressed from GD7 to GD21, METH pharmacokinetic values significantly increased (p<0.05) for area under the METH serum concentration versus time curve (18,075 vs. 21,156 kg‐min/ml) volume of distribution (5 vs. 7 L/kg), and terminal elimination half‐life (86 vs. 116 min). In contrast, systemic and non‐renal clearance significantly decreased. In addition, the AMP metabolite half‐life nearly doubled from GD7 (100 min) to GD21 (191 min). These data suggest that METH and AMP pharmacokinetics are dependent upon gestational time. If similar changes were found in humans, they could impact mothers and their unborn children. (Funded by NIDA grant DA07610 and GlaxoSmithKline Fellowship).