Practical Considerations When Designing and Conducting Clinical Pharmacokinetic Herb–Drug Interaction Studies

Abstract

Pharmacokinetic herb–drug interaction (HDI) research has been ongoing for almost two decades and a significant body of information has been published on the subject, yet much of it is contradictory. Some of this disparity stems from the botanical dosage form itself, as product quality and dosage form performance can vary significantly among brands. Unless products are adequately characterized, HDI study results can be misleading. The purpose of this report is to identify several common weaknesses inherent in many prospective clinical HDI studies and to provide guidance in addressing these shortcomings. Topics such as study design, pharmacokinetic end points, product quality, dosage form performance, gauging clinical relevance, and efforts to minimize dietary influences while improving compliance are discussed.

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“…Of two available studies utilizing a probe drug approach, it appears that the activities of CYP1A2, CYP2D6, CYP2C9, and CYP3A4 enzymes are unlikely to be significantly influenced by modest GTE exposure [37,50]. This finding is generally at odds with in vitro reports, which suggested metabolic inhibition, but the disparate findings of in vitro vs. in vivo studies is not an uncommon finding in the field of botanical-drug interaction assessment [41].…”

“…Not Intended to Diagnose, Treat, Cure or Prevent Any Disease.” 25 Years of Botanical Dietary Supplement Research and the Lessons Learned

“…Furthermore, the results from rodent HDI studies may not always coincide with clinical findings. There are a number of limitations of murine HDI studies, species variation in metabolism and transport being the most obvious . In vitro assays and murine studies can, however, be useful in selecting BDS that may warrant further clinical evaluation.…”

An Appraisal of Drug-Drug Interactions with Green Tea (Camellia sinensis)

“…Patients typically receive the probe medications (representing the potential "victim" drug) on two occasions, once alone, and a second time concurrently with the suspected "perpetrator" agent (e.g., GTE). On both occasions serial blood concentrations are measured to enable investigators to determine if the suspected offending agent exerted any influence on the disposition of the respective probe drug [50]. Formal clinical studies are highlighted in ▶ Table 4.…”

“…To date, only a few clinical pharmacokinetic studies have been conducted in human subjects. Of two available studies utilizing a probe drug approach, it appears that the activities of CYP1A2, CYP2D6, CYP2C9, and CYP3A4 enzymes are unlikely to be significantly influenced by modest GTE exposure [37,50]. This finding is generally at odds with in vitro reports, which suggested metabolic inhibition, but the disparate findings of in vitro vs. in vivo studies is not an uncommon finding in the field of botanical-drug interaction assessment [41].…”