Rasagiline Pharmacokinetics in CYP1A2 Variant Healthy Smokers & Non-smokers in Different Doses

Rabiea Bilal; Naseem Saud Ahmad; Sehrish Zaffar; Muhammad Usama Mazhar; Waqar Ahmed Siddiqui; Saba Tariq

doi:10.12669/pjms.38.3.4940

Rabiea Bilal CMH Lahore Medical College & Institute of Dentistry, NUMS
Naseem Saud Ahmad University of Health Sciences (UHS) Lahore, Pakistan
Sehrish Zaffar CMH Lahore Medical College & Institute of Dentistry, NUMS
Muhammad Usama Mazhar CMH Lahore Medical College & Institute of Dentistry, NUMS
Waqar Ahmed Siddiqui CMH Lahore Medical College & Institute of Dentistry, NUMS
Saba Tariq University Medical & Dental College, The University of Faisalabad, Pakistan.

DOI: https://doi.org/10.12669/pjms.38.3.4940

Keywords: Bioavailability, Drug disposition, Genetic variation, Pharmacokinetics, Smokers

Abstract

Objectives: Rasagiline, a drug for Parkinson’s disease is metabolized by CYP1A2 enzyme. The objective of the study was to investigate the influence of cytochrome P450 1A2 variants and smoking status of healthy individuals on the pharmacokinetics of rasagiline.

Methods: A comparative, open label, interventional, single oral dose, pharmacokinetic study was performed on 108 healthy volunteers in UHS & UVAS, Lahore. Data collection was initiated in June 2016 and ended in January 2018. It was divided in three phases with 1, 2 and 5mg of rasagiline given to a group of 36 volunteers in each phase. Volunteers were sub-divided into six groups of AA smokers, AA non-smokers, AC smokers, AC non-smokers, CC smokers & CC non-smokers on the basis of genotyping and smoking status. Serial blood sampling was performed at 0, 0.25, 0.5, 0.75, 1, 1.5, 2, 3, 4, 6, 8 & 12 hours after administration of rasagiline tablets. Plasma concentrations were determined using High Performance Liquid Chromatography (HPLC) method. Pharmacokinetic (PK) parameters were calculated using software (APO) pharmacological analysis.

Results: Analysis of variance (ANOVA) showed significant difference between AA and CC groups. Multiple group comparison with post hoc Tukey’s revealed that AA-smokers had significantly less tmax (p<0.001), t1/2 (p<0.012), AUC (p<0.008) and highest Cl (p<0.001) as compared to CC-smokers. The trend was same across all three doses.

Conclusion: The study concludes that the systemic metabolism of rasagiline is significantly increased in CYP1A2*AA variants while smoking status did not show consistent difference in PK parameters.

Registered Trial: ISRCTN68198254

doi: https://doi.org/10.12669/pjms.38.3.4940

How to cite this:
Bilal R, Ahmad NS, Zaffar S, Mazhar MU, Siddiqui WA, Tariq S. Rasagiline Pharmacokinetics in CYP1A2 Variant Healthy Smokers & Non-smokers in Different Doses. Pak J Med Sci. 2022;38(3):589-594. doi: https://doi.org/10.12669/pjms.38.3.4940

This is an Open Access article distributed under the terms of the Creative Commons Attribution License (http://creativecommons.org/licenses/by/3.0), which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited.