RT Journal Article
SR Electronic
T1 Selection of Priority Natural Products for Evaluation as Potential Precipitants of Natural Product-Drug Interactions: a NaPDI Center Recommended Approach
JF Drug Metabolism and Disposition
JO Drug Metab Dispos
FD American Society for Pharmacology and Experimental Therapeutics
SP dmd.118.081273
DO 10.1124/dmd.118.081273
A1 Emily J. Johnson
A1 Vanessa Gonzalez-Perez
A1 Dan-Dan Tian
A1 Yvonne S. Lin
A1 Jashvant D. Unadkat
A1 Allan E. Rettie
A1 Danny D. Shen
A1 Jeannine S. McCune
A1 Mary F. Paine
YR 2018
UL http://dmd.aspetjournals.org/content/early/2018/05/07/dmd.118.081273.abstract
AB 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.