uu.seUppsala University Publications
Change search
ReferencesLink to record
Permanent link

Direct link
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
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
Educational program
Master of Science Programme in Pharmacy
Available from: 2016-09-14 Created: 2016-09-14 Last updated: 2016-09-14Bibliographically approved

Open Access in DiVA

No full text

Search in DiVA

By author/editor
Smedshammar, Emelie
By organisation
Department of Pharmaceutical Biosciences
Pharmaceutical Sciences

Search outside of DiVA

GoogleGoogle Scholar
The number of downloads is the sum of all downloads of full texts. It may include eg previous versions that are now no longer available

ReferencesLink to record
Permanent link

Direct link