4.1. Pharmacokinetic Interactions
Predicting pharmacokinetic herb-drug interactions is difficult because the pharmacological actions of the interacting drugs are often not related. This is also the case with the subject of this review, valerian as a treatment of insomnia, and chemically defined cytostatic therapies. Herb-drug interactions can occur on the levels of absorption, distribution, metabolism, or excretion and can change the amount and duration of the availability of a drug at the site of action. The interactions due to drug metabolism can be, as mentioned above, based on phase 1 metabolism (mainly involving cytochrome P 450 isoenzymes) or, rather rare, on phase 2 metabolism involving, for example, P-glycoproteins (P-gp), which is relevant for outward bound transport processes, for example, in the intestinal wall, or on conjugation, for example, with glucuronic acid [43]. In case that a specific herb-drug interaction is identified, its clinical significance depends on the degree of accumulation and the therapeutic window of the respective drug [44]. Also the dosage, time of administration, galenic properties, and coadministration as well as intrinsic and extrinsic factors may be of importance.