CYP1A2'de Rasagiline Farmakokinetiği Farklı Dozlarda Varyant Sağlıklı Sigara İçenler ve Sigara İçenler.

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ObjectivesRasagiline, 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.MethodsA 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.ResultsAnalysis 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 (p1/2 (pConclusionThe 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.

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