Pharmacokinetic and pharmacodynamic studies of cytisine – a smoking cessation medicine
Independent thesis Advanced level (degree of Master (Two Years)), 20 credits / 30 HE creditsStudent thesis
Introduction: The use of tobacco is the greatest cause of preventable deaths in the world. Cytisine is a partial agonist at the α4β2 nicotinic acetylcholine receptor (nAChR). It is a low cost, smoking cessation treatment which has been used in Eastern Europe since the 1960’s. It has been shown to havesimilar efficacy to varenicline, another α4β2-nAChR partial agonist, and to be well tolerated. Despite decades of use, there are significant gaps in the knowledge around human pharmacokinetics, concentration-effect-relationship and tolerability. The elements of this project formed part of the C-DRAKS trials investigating these areas.
Aims: A. To develop, validate and perform an HPLC-UV assay for external quality control of the amount of cytisine present in the drug Desmoxan®. B. To generate a model predicting the plasma concentrations of cytisine in the participants throughout a one day, single dose trial and afive day multi dose trial of cytisine with three different dosing regimens.
Materials and Methods: A. The assay was developed using a reversed phase C18 column with an isocratic mobile phase of 50 mM ammonium formate buffer, pH 4.5 and acetonitrile (ACN) 92.5:7.5 (v/v). Cytisine was monitored at 310 nm and the internal standard at 260 nm. B. The predictive modelling was conducted usingthe Berkeley Madonna software.
Results: A. The average cytisine content in Desmoxan® was calculated to be 1.38±0.08 mg (1.5 mg stated) which is within the acceptable range. B. Plasma concentrations of cytisine would be expected to accumulate over the 5 days of multidose studies and Cmax on day 5 to be the same in the three groups.
Conclusions: The plasma concentrations at days 4-5 of the multidose study may be higher than ever recorded, which makes close monitoring of potential adverse effects very important.
Place, publisher, year, edition, pages
2016. , 23 p.
cytisine, pharmacokinetics, HPLC, smoking cessation, smoking cessation treatment, quit smoking, PK modelling
IdentifiersURN: urn:nbn:se:uu:diva-302973OAI: oai:DiVA.org:uu-302973DiVA: diva2:970517
The University of Auckland, Auckland, New Zealand; -
Subject / course
Master of Science Programme in Pharmacy
Sheridan, Janie, Professor
Hammarlund-Udenaes, Margareta, Professor