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Pharmacokinetic and pharmacodynamic studies of cytisine – a smoking cessation medicine
Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Pharmacy, Department of Pharmaceutical Biosciences.
2016 (English)Independent thesis Advanced level (degree of Master (Two Years)), 20 credits / 30 HE creditsStudent thesis
Abstract [en]

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.
Keyword [en]
cytisine, pharmacokinetics, HPLC, smoking cessation, smoking cessation treatment, quit smoking, PK modelling
National Category
Pharmaceutical Sciences
Identifiers
URN: urn:nbn:se:uu:diva-302973OAI: oai:DiVA.org:uu-302973DiVA: diva2:970517
External cooperation
The University of Auckland, Auckland, New Zealand; -
Subject / course
Pharmacokinetics
Educational program
Master of Science Programme in Pharmacy
Supervisors
Examiners
Available from: 2016-09-14 Created: 2016-09-14 Last updated: 2016-09-14Bibliographically approved

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