Pharmacokinetic interactions between drugs and botanical dietary supplements

Abstract

The use of botanical dietary supplements has grown steadily over the last 20 years despite incomplete information regarding active constituents, mechanisms of action, efficacy, and safety. An important but underinvestigated safety concern is the potential for popular botanical dietary supplements to interfere with the absorption, transport, and/or metabolism of pharmaceutical agents. Clinical trials of drug-botanical interactions are the gold standard and are usually carried out only when indicated by unexpected consumer side effects or, preferably, by predictive preclinical studies. For example, phase 1 clinical trials have confirmed preclinical studies and clinical case reports that St. John's wort (Hypericum perforatum) induces CYP3A4/CYP3A5.However, clinical studies of most botanicals that were predicted to interact with drugs have shown no clinically significant effects. For example, clinical trials did not substantiate preclinical predictions that milk thistle (Silybum marianum) would inhibit CYP1A2, CYP2C9, CYP2D6, CYP2E1, and/or CYP3A4. Here, we highlight discrepancies between preclinical and clinical data concerning drug-botanical interactions and critically evaluate why some preclinical models perform better than others in predicting the potential for drug-botanical interactions. Gaps in knowledge are also highlighted for the potential of some popular botanical dietary supplements to interact with therapeutic agents with respect to absorption, transport, and metabolism.

Critical evaluation of causality assessment of herb–drug interactions in patients

“…However, preclinical investigations often do not correlate with findings in human subjects [23][24][25][26][27]. Clinical studies in patients adopting a population pharmacokinetic approach is considered as the gold standard to determine the clinical consequences of potential interaction of herbal medicines with prescribed medications [28]. Nevertheless, pharmacokinetic interaction studies are often conducted in healthy subjects [29,30].…”

Potential Interactions of Biologically Based Complementary Medicine in Gynecological Oncology

“…This may lead to subtherapeutic drug levels in the body as well as to prolonged activity and even toxicity of a drug. 23 Preclinical studies are essential to determine possible CDIs, but clinical trials have to prove whether these results are of clinical relevance to human health or not. For instance, preclinical data followed by clinical studies verified the danger of the well-documented pharmacokinetic interaction between SJW and drugs metabolized by CYP3A4.…”

“…Table 3 illustrates potential pharmacokinetic interactions between anticancer drugs and herbs. 17,18,[23][24][25][26][27][28][29][30][31][32] In 82 patients (82/448, 18.3%), those CDIs were evaluated on a pharmacokinetic basis that were suspected to have interactions with the metabolism of cytochrome P450 (CYP) enzymes and most frequently of CYP3A4 (Figure 1).…”

Restarting antidepressant and antipsychotic medication after intentional overdoses: need for evidence-based guidance

“…Although not widely used in present-day management of depression, it is of note that prolonged recovery may be produced by combinations of MAOIs and other drugs. On the other hand, induction of CYP3A4 occurs after chronic usage of other unrelated drugs, such as carbamazepine, phenytoin, rifampicin and herbal preparations such as St John’s wort ( Hypericum perforatum ), 72 with predicted faster recovery times after overdosage of drugs metabolized by CYP3A4. Fluvox-amine also prolongs the half-lives of drugs and consequently slows the recovery from drugs metabolized by CYP1A2 and CYP2C19 (Table 2).…”