Pharmacokinetics of cytisine after single intravenous and oral administration in rabbits

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Pharmacokinetics of cytisine after single intravenous and oral administration in rabbits

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.

Bioanalytical method validation. (2001). Guidance for industry. FDA/CDER/CVM/DHHS.

Coe J, Brooks P, Vetelino M, Wirtz M, Arnold E, Huang J, Sands S, Davis T, Lebel L, Fox C, Shrinkhande A, Heym J, Schaeffer E, Rollema H, Lu Y, Mansbach R, Chambers L, Rovetti C, and Schulz D. (2005). Varenicline: an alpha4beta2 nicotinic receptor partial agonist for smoking cessation. J Med Chem 48: 3474-3477.

Dobreva D, Danchev N, Nikolova I. (2005). Tabex - Sopharma - natural alternative for smoking cessation and treatment of nicotine dependence. Pharmacia 52: 30-35.

Gonzales D, Rennard S, Nides M, Oncken C, Azoulay S, Billing C, Watsky E, Gong J, Williams K and Reeves K. (2006). Varenicline, an alpha4beta2 nicotinic acetylocholine receptor partial agonist, vs. sustained-release bupropion and placebo for smoking cessation. A randomized controlled trial. JAMA 296: 47-55.

Imming P, Klaperski P, Stubbs M, Seitz G and Gündisch D. (2001). Syntheses and evaluation of halogenated cytisine derivatives and of bioisosteric thiocytisine as potent and selective nAChR ligands. Eur J Med Chem 36: 375-388.

Jorenby D, Hays J, Rigotti N, Azoulay S, Watsky E, Williams K, Billing C, Gong J and Reeves K. (2006). Efficacy of varenicline, an α4β2-nicotinic acetylcholine receptor partial agonist, vs. placebo or sustained-release bupropion for smoking cessation. A randomized controlled trial. JAMA 296: 56-63.

Klocking H, Richter M, and Damm G. (1980). Pharmacokinetic studies with 3Hcytisine. Arch Toxicol Suppl 4: 312-4.

Lickint F. (1956). Medikamentöse Unterstützung der Tabakenwöhnung. Therapiewoche 6: 444-448.

Mokdad A, Marks J, Stroup D and Gerberding J. (2004). Actual causes of death in the United States. JAMA 291: 1238-1245.

Sariev A, V Zherdev V, Sologova S, Litvin A, Rodionov A, Kolyvanov G and Vasilev A. (1999). Cytisine pharmacokinetics when used in a transdermal therapeutic system in rabbits. Exp Clin Pharmacol 62: 59-61.

Tonstad S, Tønnesen P, Hajek P, Williams K, Billing C and Reeves K. (2006). Effect of maintenance therapy with varenicline on smoking cessation. A randomized controlled trial. JAMA 296: 64-71.

Interdisciplinary Toxicology

The Journal of Institute of Experimental Pharmacology of Slovak Academy of Sciences

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CiteScore 2018: 1.78

SCImago Journal Rank (SJR) 2018: 0.274
Source Normalized Impact per Paper (SNIP) 2018: 0.671

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