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 1046
OP 1052
DO 10.1124/dmd.118.081273
VO 46
IS 7
A1 Emily J. Johnson
A1 Vanessa González-Peréz
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/46/7/1046.abstract
AB Pharmacokinetic interactions between natural products (NPs) and conventional medications (prescription and nonprescription) 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 vs. time curve, respectively), as well as mechanistic and descriptive in vitro and clinical 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.