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Smoking cessation can alter these metabolic processes, increasing the risk of ADRs or lack of therapeutic efficacy ( While the interactions between tobacco smoking and medications such as antipsychotics, antidepressants, and anticoagulants are relatively well-documented, especially in certain groups of individuals ( Pioglitazone undergoes extensive metabolism in the liver through hydroxylation and oxidation, leading to four primary metabolites (M-I, M-II, M-IV, and M-V) and two secondary metabolites (M-III and M-VI), with M-III being derived from M-IV ( In vitro studies indicate that CYP2C8 primarily metabolizes pioglitazone, with a lesser role for CYP3A4 (Muschler et al., 2009)

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