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Effect of Smoking on Pharmacokinetics of Clopidogrel, an Antiplatelet Drug
Abstract
Purpose: To assess the influence of smoking cigarettes on the pharmacokinetics of the antiplatelet drug, clopidogrel.
Methods: Thirty four male patients, mean age and weight of 59.3 years and 81.1 kg, respectively, who underwent percutaneous coronary intervention (PCI), took part in the study. Each subject received an oral loading dose of 600 mg clopidogrel eight tablets, each 75 mg). Clopidogrel carboxylate plasma level was measured and non-compartmental analysis was used to determine peak plasma concentration (Cmax), time to achieve peak plasma concentration (Tmax), elimination half-life (t1/2e), and area under the curve (AUC0-∞). Other parameters measured include gamma-glutamyltransferase enzyme (GGT), low density lipoprotein cholesterol (LDL-cholesterol), blood urea nitrogen (BUN) and platelet count.
Results: Nineteen patients were smokers (55.9 %). Smokers had higher levels of GGT compared to non-smokers (31.73 ± 14.42 vs. 21.63 ± 11.41 IU/L, p = 0.08) as well as higher levels of LDL-cholesterol (116.79 ± 42.08 vs. 87.07 ± 27.34 mg/dl, p = 0.041, respectively). Smokers had shorter half-life (smokers: 3.47 ± 1.9 h vs. non-smokers: 5.83 ± 4.09 h, p = 0.012). Smoking behavior had no influence on Cmax (p = 0.16), AUC0-∞ (p = 0.65) or Tmax (p = 0.91). In general, the pharmacokinetic parameters were characterized by considerable inter-individual variation (Cmax = 23.2 ± 8.79 μg/ml, coefficient of variation (CV) = 37.9 %), (Tmax = 1.71 ± 1.15 h, CV = 67.2 %), (AUC0-∞ = 120.97 ± 44.4 μg.h/ml, CV = 36.7 %) and (t1/2e = 4.57 ± 3.15 h, CV = 68.9 %).
Conclusion: Smoking behavior may not be a significant determinant of the pharmacokinetics of clopidogrel following oral administration of 600 mg dose in patients undergoing PCI.
Keywords: Antiplatelet, Clopidogrel, Pharmacokinetics, Smoking, Cigarette
