Gender Differences in the Pharmacokinetics of Rivastigmine in Rats

Abstract

The effect of gender on the pharmacokinetics of rivastigmine (CAS 123441-03-2) was studied in male and female Wistar rats following intravenous bolus administration. The area under the plasma concentration-time curve (AUC), apparent volume of distribution (Vd), systemic clearance (CL), and terminal plasma half-life (t_1/2) of rivastigmine were compared between male and female rats. Compared to male rats, female rats exhibited higher plasma rivastigmine levels showing significantly (p < 0.05) larger AUC (226.77 vs. 149.68 ng h/ml), V_d (6.70 vs. 4.13 L), t_1/2 (0.84 vs. 0.34 h) and a lower CL (5.51 vs. 8.35 L/h).

The male rats had a 2.5 fold greater elimination rate constant than female rats (2.02 vs. 0.82 h⁻¹). Gender had a significant effect on the pharmacokinetics of rivastigmine. Gender differences were reported due to gonadal hormones, and the observed difference in pharmacokinetics of rivastigmine might be attributed to testosterone in male rats.

Key words

Acetylcholine esterase inhibitor - CAS 123441-03-2 - Rivastigmine, gender differences, pharmacokinetics

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