PMID- 24670388
OWN - NLM
STAT- PubMed-not-MEDLINE
DCOM- 20140327
LR  - 20211021
IS  - 2163-8306 (Print)
IS  - 2163-8306 (Electronic)
IS  - 2163-8306 (Linking)
VI  - 3
IP  - 3
DP  - 2014 Mar 26
TI  - Physiologically based pharmacokinetic modeling framework for quantitative 
      prediction of an herb-drug interaction.
PG  - e107
LID - 10.1038/psp.2013.69 [doi]
AB  - Herb-drug interaction predictions remain challenging. Physiologically based 
      pharmacokinetic (PBPK) modeling was used to improve prediction accuracy of 
      potential herb-drug interactions using the semipurified milk thistle preparation, 
      silibinin, as an exemplar herbal product. Interactions between silibinin 
      constituents and the probe substrates warfarin (CYP2C9) and midazolam (CYP3A) 
      were simulated. A low silibinin dose (160 mg/day x 14 days) was predicted to 
      increase midazolam area under the curve (AUC) by 1%, which was corroborated with 
      external data; a higher dose (1,650 mg/day x 7 days) was predicted to increase 
      midazolam and (S)-warfarin AUC by 5% and 4%, respectively. A proof-of-concept 
      clinical study confirmed minimal interaction between high-dose silibinin and both 
      midazolam and (S)-warfarin (9 and 13% increase in AUC, respectively). 
      Unexpectedly, (R)-warfarin AUC decreased (by 15%), but this is unlikely to be 
      clinically important. Application of this PBPK modeling framework to other 
      herb-drug interactions could facilitate development of guidelines for 
      quantitative prediction of clinically relevant interactions.CPT Pharmacometrics 
      Syst. Pharmacol. (2014) 3, e107; doi:10.1038/psp.2013.69; advance online 
      publication 26 March 2014.
FAU - Brantley, S J
AU  - Brantley SJ
AD  - Eshelman School of Pharmacy, The University of North Carolina at Chapel Hill, 
      Chapel Hill, North Carolina, USA.
FAU - Gufford, B T
AU  - Gufford BT
AD  - College of Pharmacy, Washington State University, Spokane, Washington, USA.
FAU - Dua, R
AU  - Dua R
AD  - Eshelman School of Pharmacy, The University of North Carolina at Chapel Hill, 
      Chapel Hill, North Carolina, USA.
FAU - Fediuk, D J
AU  - Fediuk DJ
AD  - Eshelman School of Pharmacy, The University of North Carolina at Chapel Hill, 
      Chapel Hill, North Carolina, USA.
FAU - Graf, T N
AU  - Graf TN
AD  - Department of Chemistry and Biochemistry, The University of North Carolina at 
      Greensboro, Greensboro, North Carolina, USA.
FAU - Scarlett, Y V
AU  - Scarlett YV
AD  - School of Medicine, The University of North Carolina at Chapel Hill, Chapel Hill, 
      North Carolina, USA.
FAU - Frederick, K S
AU  - Frederick KS
AD  - Boehringer Ingelheim Pharmaceuticals, Inc., Ridgefield, Connecticut, USA.
FAU - Fisher, M B
AU  - Fisher MB
AD  - ProPharma Services, LLC, Oxford, Connecticut, USA.
FAU - Oberlies, N H
AU  - Oberlies NH
AD  - Department of Chemistry and Biochemistry, The University of North Carolina at 
      Greensboro, Greensboro, North Carolina, USA.
FAU - Paine, M F
AU  - Paine MF
AD  - College of Pharmacy, Washington State University, Spokane, Washington, USA.
LA  - eng
GR  - R01 GM077482/GM/NIGMS NIH HHS/United States
GR  - UL1 TR000083/TR/NCATS NIH HHS/United States
PT  - Journal Article
DEP - 20140326
PL  - United States
TA  - CPT Pharmacometrics Syst Pharmacol
JT  - CPT: pharmacometrics & systems pharmacology
JID - 101580011
PMC - PMC4042458
EDAT- 2014/03/29 06:00
MHDA- 2014/03/29 06:01
PMCR- 2014/03/01
CRDT- 2014/03/28 06:00
PHST- 2013/08/12 00:00 [received]
PHST- 2013/10/28 00:00 [accepted]
PHST- 2014/03/28 06:00 [entrez]
PHST- 2014/03/29 06:00 [pubmed]
PHST- 2014/03/29 06:01 [medline]
PHST- 2014/03/01 00:00 [pmc-release]
AID - psp201369 [pii]
AID - 10.1038/psp.2013.69 [doi]
PST - epublish
SO  - CPT Pharmacometrics Syst Pharmacol. 2014 Mar 26;3(3):e107. doi: 
      10.1038/psp.2013.69.