The pharmacokinetics and bioavailability of dihydroergotoxine mesylate after nasal administration to rats

Purpose: To prepare different dihydroergotoxine mesylate (DHETM) nasal formulations and study their pharmacokinetics in rats after nasal administration. Methods: DHETM was nasally administered at doses of 2 and 4 mg/kg. An HPLC fl uorometric method was used to measure the concentrations of DHETM in rat plasma. A non-compartmental statistical moment method was used to analyse the pharmacokinetics data, and the absolute bioavailability of nasal administration was calculated by comparison with DHETM intravenous injection. Results: Tmax, Cmax, MRT values and absolute bioavailability of group I (2 and 4 mg/kg), II (4 mg/kg), III (4 mg/kg) were 110, 110, 110 and 55 min; 257.84, 361.89, 299.41 and 246.22 ng/ml; 137.00, 140.06, 130.92 and 76.80 min; 35.81%, 25.52%, 20.21% and 11.64%, respectively. The MRT, CL and Vss after i.v. administration (2 mg/kg) to rats were 195.29 min, 0.1220 l/min⋅kg and 4.32 l/kg, respectively. Conclusion: The absolute bioavailability of both 2.00 and 4.00 mg/kg in group I were higher than that group II and III, which indicated that some of the adjuncts could enhance the bioavailability of DHETM.