Cigarette smoking induces cytochrome P450 1A2 (CYP1A2) expression and activity, while smoking cessation normalizes the levels of this enzyme. The aim of this publication is to summarize the data on CYP1A2 gene expression and activity in preclinical and clinical studies on the Tobacco Heating System (THS), currently marketed as IQOS® with HEETs®, and to summarize the potential effects on CYP1A2 to be expected upon switching to reduced-risk products (RRPs).To get more news about HNB, you can visit hitaste.net official website.

Data from four preclinical mouse and rat studies showed that, upon either cessation of cigarette smoke exposure or switching to THS exposure, the upregulation of CYP1A2 observed with exposure to cigarette smoke reverted close to fresh-air levels. Data from four clinical studies yielded similar results on CYP1A2 activity within a time frame of five days. Furthermore, the effects of switching to THS were similar to those seen after smoking cessation. Because smoking cessation and switching to either electronic cigarettes or THS seem to have similar effects on CYP1A2 activity, the same measures taken for patients treated with narrow therapeutic index drugs that are metabolized by CYP1A2 and who quit smoking should be recommended for those switching to RRPs.

The cytochrome P450 (CYP) family of mono-oxygenases are important enzymes involved in the metabolism of drugs, pesticides, and endogenous metabolites [1]. Of these, human CYP1A enzymes should be considered not only in pharmacology but also in physiopathology, as they are involved in the detoxification of drugs as well as metabolic activators of harmful xenobiotics, such as aromatic amines and heterocyclic aromatic amines, that have carcinogenic potential [2,3]. There are two CYP1A isoforms expressed in humans out of which CYP1A2 is preferentially expressed and accounts for 13–15 % of the total hepatic CYP content, while CYP1A1 is considered an extrahepatic enzyme in humans [[2], [3], [4]]. Furthermore, there is no evidence of expression of CYP1A2 in extrahepatic tissues [5]. CYP1A2 is involved in the metabolism of about 9% of marketed drugs [3], such as theophylline [6], propranolol [7], verapamil [8], and clozapine [9], among others. Plasma concentrations of such drugs, therefore, depend on the activity of this enzyme [10]. Because some of the medications metabolized by CYP1A2 have a narrow therapeutic index (e.g., theophylline and clozapine), actual individual enzyme activity may have an important effect on their efficacy and tolerability, and a correspondingly individualized dose is often required for such drugs. Large inter- and intra-individual variability of CYP1A2 activity has been observed in humans [11]. This variability is partly because CYP1A2 is induced or inhibited by other drugs, environmental compounds, and dietary or lifestyle-related factors.

Cigarette smoking, for instance, has been shown to induce CYP1A2 activity, which has been quantified to be 1.72-fold higher in heavy smokers (≥20 cigarettes per day) compared to nonsmokers [12]. Additionally, sudden smoking cessation and the subsequent abolishment of CYP1A2 induction could lead to adverse drug reactions [10]. Case reports describing adverse reactions caused by elevated concentrations of different drugs after smoking cessation suggest that dose adjustment should be conducted whenever patients cease smoking while under treatment with CYP1A2-metabolized drugs, particularly those with narrow therapeutic indices [[13], [14], [15], [16], [17]]. Specifically, it is the exposure to polycyclic amino hydrocarbons (PAHs) which are products of incomplete combustion of organic matter through tobacco smoking that results in the induction of drug-metabolizing enzymes [2]. Because the effect on hepatic microsomal enzymes is not related to the nicotine component of tobacco, nicotine replacement will not alter this effect [18].