Journal article
Effect of a herbal extract containing curcumin and piperine on midazolam, flurbiprofen and paracetamol (acetaminophen) pharmacokinetics in healthy volunteers
British journal of clinical pharmacology, Vol.75(2), pp.450-462
02/2013
Handle:
https://hdl.handle.net/2376/104787
PMCID: PMC3579260
PMID: 22725836
Abstract
Aims
Turmeric extract derived curcuminoids (curcumin, demethoxycurcumin and bisdemethoxycurcumin) are currently being evaluated for the treatment of cancer and Alzheimer's dementia. Previous in vitro studies indicate that curcuminoids and piperine (a black pepper derivative that enhances curcuminoid bioavailability) could inhibit human CYP3A, CYP2C9, UGT and SULT dependent drug metabolism. The aim of this study was to determine whether a commercially available curcuminoid/piperine extract alters the pharmacokinetic disposition of probe drugs for these enzymes in human volunteers.
Methods
A randomized placebo‐controlled six way crossover study was conducted in eight healthy volunteers. A standardized curcuminoid/piperine preparation (4 g curcuminoids plus 24 mg piperine) or matched placebo was given orally four times over 2 days before oral administration of midazolam (CYP3A probe), flurbiprofen (CYP2C9 probe) or paracetamol (acetaminophen) (dual UGT and SULT probe). Plasma and urine concentrations of drugs, metabolites and herbals were measured by HPLC. Subject sedation and electroencephalograph effects were also measured following midazolam dosing.
Results
Compared with placebo, the curcuminoid/piperine treatment produced no meaningful changes in plasma Cmax, AUC, clearance, elimination half‐life or metabolite levels of midazolam, flurbiprofen or paracetamol (α = 0.05, paired t‐tests). There was also no effect of curcuminoid/piperine treatment on the pharmacodynamics of midazolam. Although curcuminoid and piperine concentrations were readily measured in plasma following glucuronidase/sulfatase treatment, unconjugated concentrations were consistently below the assay thresholds (0.05–0.08 μm and 0.6 μm, respectively).
Conclusion
The results indicate that short term use of this piperine‐enhanced curcuminoid preparation is unlikely to result in a clinically significant interaction involving CYP3A, CYP2C9 or the paracetamol conjugation enzymes.
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Details
- Title
- Effect of a herbal extract containing curcumin and piperine on midazolam, flurbiprofen and paracetamol (acetaminophen) pharmacokinetics in healthy volunteers
- Creators
- Laurie P Volak - Sackler School of Graduate Biomedical Sciences, Tufts UniversityMichael J Hanley - Sackler School of Graduate Biomedical Sciences, Tufts UniversityGina Masse - Tufts University School of MedicineSuwagmani Hazarika - Tufts University School of MedicineJerold S Harmatz - Tufts University School of MedicineVladimir Badmaev - Sabinsa CorporationMuhammed Majeed - Sabinsa CorporationDavid J Greenblatt - Tufts University School of MedicineMichael H Court - Tufts University School of Medicine
- Publication Details
- British journal of clinical pharmacology, Vol.75(2), pp.450-462
- Academic Unit
- Veterinary Clinical Sciences, Department of
- Number of pages
- 13
- Grant note
- Alternative Medicine (NCCAM) (F31AT060682) National Center for Complementary (F31AT003973) National Institute of General Medical Sciences (NIGMS) (R01GM061834) National Institutes of Health
- Identifiers
- 99900546713201842
- Language
- English
- Resource Type
- Journal article