Pharmacogenetic studies uses genetic information to determine right drug for the right patient in right dose hence maximize drug efficacy and minimize adverse drug reactions. The present Pharmacogenetic study aimed to analyze the difference in plasma levels of Cetirizine and Levocetirizine in smokers and nonsmokers from with different polymorphic forms of CYP1A2 variants (wild type AA, heterozygous AC/CA and variant CC) belonging from Pashtun ethnic population Khyber Pakhtunkhwa, Pakistan. Volunteers with history of heavy smoking were enrolled for study in the age range of 15-35 years. Blood level of Cetirizine and Levocetirizine were determined on their respective T max using High Performance Liquid Chromatography (HPLC). Restriction Fragment Length Polymorphism was used for Genotyping. The Extraction and amplification of Genomic DNA was done using DNA extraction kit (Thermo Scientific, UK). Restriction enzyme Bsp120I was used for digestion of PCR products. The plasma levels of subject population was genotyped for CYP1A2 variants; wild type AA, heterozygous AC/CA and variant CC to get an inference for optimal therapeutic response in genetic perspective. Variation and frequency of alleles was calculated using one-way ANOVA and Hardy Weinberg Equation among different genotypes in smokers and non-smokers. The plasma concentration of Cetirizine was 83.80-±7.7 ng /ml and 98.54-±2.85 ng/ml in smokers and non-smokers respectively. The difference in plasma concentration of Cetirizine in smokers and non-smokers was significant with p-value of 0.027 (p < 0.05). The plasma concentration of Levocetirizine was 97.50 ±14.79 ng /ml and 99.40 ± 6.55 ng/ml in smokers and non-smokers respectively. The difference in plasma concentration of Levocetirizine in smokers and non-smokers was not significant with p- value of 0.069 (p < 0.05). The frequency of CYP1A2 variants (wild type AA, heterozygous AC/CA and variant CC) was 78.22%, 19.56% and 2.22% in Pashtun population respectively. The metabolism of Levocetirizine was observed at a higher rate in volunteers having heterozygous genotypes (AC/CA) of CYP1A2 gene. Smokers with different polymorphic forms of CYP1A2 gene showed significant difference in plasma concentration of Levocetirizine with p-value of 0.0003 (p<0.05). The findings of the present study suggests that in smokers polymorphic forms of CYP1A2 affects plasma levels of Levocetirizine while the plasma levels of Cetirizine is not affected.