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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):---------. 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.

Introduction Astragalus species have been widely used in Chinese herbal medicine to treat gastrointestinal and inflammatory disorders. This study was conducted to evaluate the efficacy of Astragalus sarcocolla (ASE) and to rationalize its medicinal use as an antispasmodic drug for the treatment of spasmodic gastrointestinal and inflammatory disorders associated with increased intestinal motility. Methods The ethanolic extract of ASE was studied to examine its antispasmodic effect on the isolated rabbit ileum preparations, and the contractions were recorded on PowerLab (ADInstruments, Sydney, Australia). Results ASE was able to inhibit spontaneous ileum contractions. It also completely inhibited K + (25 mM)-induced contractions but was unable to inhibit high K + (80 mM)-induced sustained contractions. Pretreatment of the tissue with glibenclamide, a potassium channel blocker, caused a rightward shift of the dose-response curve when stimulated with K + (25 mM) in the presence of an increasing concentration of the extract. Verapamil at very low doses inhibited both the 25 mM and 80 mM K +-induced contractions. Conclusion The results of our study demonstrated the spasmolytic activity of ASE with the potential mechanism of activation of K + ATP, which provides a strong basis for its medicinal use in motility and inflammatory disorders of the intestine.

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