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

*Corresponding author for this work

Research output: Contribution to journalArticlepeer-review

2 Citations (Scopus)
19 Downloads (Pure)

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.

Original languageEnglish
Pages (from-to)589-594
Number of pages6
JournalPakistan Journal of Medical Sciences
Volume38
Issue number3
DOIs
Publication statusPublished - 26 Jan 2022

Bibliographical note

Funding Information:
We are grateful to University of Health Sciences (UHS) Lahore, Pakistan for partly funding this project and University of Veterinary and Animal Sciences (UVAS) Lahore, Pakistan to provide us their laboratory for carrying out HPLC related work. Source of funding: Self-funded and partly by University of Health Sciences (UHS) Lahore, Pakistan.

Keywords

  • Bioavailability
  • Drug disposition
  • Genetic variation
  • Pharmacokinetics
  • Smokers

ASJC Scopus subject areas

  • General Medicine

Fingerprint

Dive into the research topics of 'Rasagiline Pharmacokinetics in CYP1A2 Variant Healthy Smokers & Non-smokers in Different Doses'. Together they form a unique fingerprint.

Cite this