**1. Introduction**

The oral bioavailability of many drugs is determined by first-pass metabolism taking place in human gu<sup>t</sup> and liver. In this regard, a considerable fraction of the administered dose is presystemically eliminated by intestinal and hepatic phase I and/or phase II drug metabolism Consequently, only a minor fraction of the administered dose reaches the central compartment and in turn the site of action. Thus, alterations of the aforementioned presystemic metabolism in terms of inhibition or induction of the involved metabolizing enzymes may result in two unwanted clinical scenarios: (1) increased drug exposure as caused by enzyme inhibition with an increased risk of side effects up to drug-related toxicity, and (2) subtherapeutic drug levels due to induction of the respective metabolizing enzymes, which may threaten the therapeutic drug effects [1,2].

During the last decades, it was clearly demonstrated that major cytochrome P450 (CYP) enzymes such as CYP3A4, CYP2C9/19, and CYP2D6 play a major role in first-pass metabolism of drugs [3–5]. Here, extensive pharmacokinetic and pharmacogenetic studies have been conducted and identified these enzymes as crucial determinants in the pharmacokinetics and, in turn, for efficacy and safety of their substrates [6–9]. However, beside these major enzymes, the information about other CYPs that are considerably expressed in the human intestine or liver and significantly involved in the metabolism of frequently used drugs is much more limited. Examples for these somewhat "under-investigated" enzymes are CYP1A1 and CYP1A2, which are involved in the metabolism of about 10% of the drugs on the market [10,11]. Despite their clinical relevance, considerably fewer studies related to human

pharmacokinetics and drug–drug interactions compared to the above-mentioned major enzymes have so far been published. For example, Medline search (via PubMed ®) on "human pharmacokinetics" and certain enzymes listed 6379 entries for CYP3A4, 2902 for CYP2C9/19, and 2794 for CYP2D6, but "only" 734 and 1749 have been found for CYP1A1 and CYP1A2, respectively (assessed 22 October, 2020). Thus, the aim of this mini review article is to provide an up-to-date overview about the current knowledge on the expression, regulation, and clinically relevant drug–drug interactions of CYP1A1 and CYP1A2 in humans.
