Abstract
Pharmacokinetic interactions between natural products (NPs) and conventional medications (prescription and non-prescription) are a longstanding but understudied problem in contemporary pharmacotherapy. Consequently, there are no established methods for selecting and prioritizing commercially available NPs to evaluate as precipitants of NP-drug interactions (NPDIs). As such, NPDI discovery remains largely a retrospective, bedside-to-bench process. This Recommended Approach, developed by the Center of Excellence for Natural Product Drug Interaction Research (NaPDI Center), describes a systematic method for selecting NPs to evaluate as precipitants of potential clinically significant pharmacokinetic NPDIs. Guided information-gathering tools were used to score, rank, and triage NPs from an initial list of 47 candidates. Triaging was based on the presence and/or absence of an NPDI identified in a clinical study (≥20% or <20% change in the object drug area under the concentration versus time curve, respectively), as well as mechanistic and descriptive in vitro and in vivo data. A qualitative decision-making tool, termed the "fulcrum model", was developed and applied to 11 high-priority NPs for rigorous study of NPDI risk. Application of this approach produced a final list of five high-priority NPs, four of which are currently under investigation by the NaPDI Center.
- cytochrome P450
- drug-drug interactions
- efflux transporters (P-gp, BCRP, MRP, MATE, BSEP, etc)
- glucuronidation/UDP-glucuronyltransferases/UGT
- hepatocytes
- human/clinical
- natural products
- pharmacokinetics
- Uptake transporters (OATP, OAT, OCT, PEPT, MCT, NTCP, ASBT, etc.)
- The American Society for Pharmacology and Experimental Therapeutics