Pharmacokinetics of cytisine after single intravenous and oral administration in rabbits

Henri Astroug,Dobrin Svinarov,Nikolay Danchev,Roumiana Simeonova,Lilia Kassabova

doi:10.2478/v10102-010-0003-5

Abstract

The aim of this study is to develop a sensitive HPLC method for the quantitative determination of cytisine in serum and to characterize the pharmacokinetic behaviour of cytisine after oral and intravenous administration in rabbits. The pharmacokinetic behaviour of cytisine is studied in male and female New Zealand rabbits after oral and intravenous administration. Cytisine is administered orally (dose of 5 mg/kg b.w.) under fasting condition (12 hours) and intravenously (dose 1 mg/kg b.w.) in the marginal ear vein. Cytisine serum concentrations are measured using a highly selective and sensitive validated HPLC method with UV detection. Linearity of the method is in the range 12–2 400 µg/L; accuracy and precision are both within ± 10%, and the limit of detection is 4 µg/L. Selectivity and stability are also validated. Basic pharmacokinetic parameters of cytisine after single oral and intravenous administration are calculated using TOPFIT software. Pharmacokinetic analysis suggests a rapid but incomplete absorption of cytisine after oral administration.

Highlights

Tobacco smoking is the first avoidable cause of deaths and morbidity in developed countries (Mokdad et al, 2004)
The aim of this study is to develop a sensitive HPLC method for the quantitative determination of cytisine in serum and to characterize the pharmacokinetic behaviour of cytisine after oral and intravenous administration in rabbits
Linearity of the method is in the range 12–2 400 μg/L; accuracy and precision are both within ± 10%, and the limit of detection is 4 μg/L

Summary

Introduction

Tobacco smoking is the first avoidable cause of deaths and morbidity in developed countries (Mokdad et al, 2004). Smoking the leaves of Cytisus laburnum L. (golden rain tree) or Ulex europaeus is proposed for the treatment of tobacco dependence in 1955 (Lickint, 1956). Tabex® is an original Bulgarian drug of plant origin, intended for treatment of nicotine dependence. The preparation is developed and introduced in 1964 on the basis of the alkaloid cytisine contained in the plant Laburnum anagyroides Medic. Cytisine possesses similar mechanism of action to that of nicotine. It excites autonomic nervous ganglia, increases adrenaline release by the adrenal gland, stimulates the locomotor center and elevates arterial blood pressure.

Objectives

Methods

Results

Conclusion