Startseite In vitro modulation of cytochrome P450 isozymes and pharmacokinetics of caffeine by extracts of Hibiscus sabdariffa Linn calyx
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In vitro modulation of cytochrome P450 isozymes and pharmacokinetics of caffeine by extracts of Hibiscus sabdariffa Linn calyx

  • Johnson Segun Showande ORCID logo EMAIL logo , Sharon Iyobor Igbinoba , Marena Kajula , Juho Hokkanen , Ari Tolonen , Olayemi Modupe Adegbolagun und Titilayo Oyelola Fakeye
Veröffentlicht/Copyright: 5. April 2019
Journal of Basic and Clinical Physiology and Pharmacology
Aus der Zeitschrift Journal of Basic and Clinical Physiology and Pharmacology Band 30 Heft 3

Abstract

Background

Hibiscus sabdariffa beverage (HSB) is widely consumed as a medicinal herb and sometimes used concomitantly with drugs. This study evaluated the in vitro inhibitory potential of the aqueous extract of H. sabdariffa calyces (AEHS) on selected cytochrome P450 (CYP) isozymes and the effect of HSB on the pharmacokinetics of caffeine in vivo.

Methods

In vitro inhibitions of eight major CYP isozymes by AEHS were estimated by monitoring CYP-specific model reactions of 10 CYP probe substrates using N-in-one assay method. Subsequently, an open, randomized, two-period crossover design was used to evaluate the effect of HSB on the pharmacokinetics of single-dose 200 mg caffeine in six healthy human volunteers. Blood samples were obtained at specific times over a 24 h period. Probe drugs and metabolites were analyzed in their respective matrices with ultra-performance liquid chromatography/mass spectrometer/mass spectrometer and reversed-phase high-performance liquid chromatography/ultraviolet detection.

Results

The H. sabdariffa aqueous extract weakly inhibited the selected CYP isozymes in vitro, with IC50 of >100 μgmL-1 in the order of CYP1A2 > CYP2C8 > CYP2B6 >> CYP2D6 > CYP2C19 > CYP3A4 > CYP2A6 > CYP2C9. HSB decreased terminal t1/2 and Tmax of caffeine by 13.6% and 13.0%, respectively, and increased Cmax by 10.3%. Point estimates of primary pharmacokinetic endpoints, Cmax = 1.142 (90% confidence interval (CI) = 0.882, 1.480) and AUC0–∞ = 0.992 (90% CI = 0.745, 1.320), were outside the 90% CI of 0.8–1.25 bioequivalence limits.

Conclusion

The aqueous extract of H. sabdariffa weakly inhibited eight CYP isozymes in vitro, but HSB modified the exposure to caffeine in human. Caution should be exercised in administering HSB with caffeine or similar substrates of CYP1A2 until more clinical data are available.

Keywords: bioequivalence; caffeine; herb-drug interaction; Hibiscus sabdariffa; human; pharmacokinetics

Acknowledgments

We would like to appreciate Late Mr. Adegoke of the Central Science Laboratory, Obafemi Awolowo University, Ile-Ife, Nigeria, Mr Seyi Olalemi, Mrs Ogunremi, and Mrs Ayorinde of the Department of Clinical Pharmacy and Pharmacy Administration Laboratory, University of Ibadan, Nigeria, for their contributions to this study.

  1. Author contributions: All the authors have accepted responsibility for the entire content of this submitted manuscript and approved submission.

  2. Research funding: None declared.

  3. Employment or leadership: None declared.

  4. Honorarium: None declared.

  5. Competing interests: The funding organization(s) played no role in the study design; in the collection, analysis, and interpretation of data; in the writing of the report; or in the decision to submit the report for publication.

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Supplementary Material

The online version of this article offers supplementary material (DOI: https://doi.org/10.1515/jbcpp-2018-0206).

Received: 2018-08-09
Accepted: 2019-01-10
Published Online: 2019-04-05

©2019 Walter de Gruyter GmbH, Berlin/Boston

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https://doi.org/10.1515/jbcpp-2018-0206
Schlagwörter für diesen Artikel
bioequivalence; caffeine; herb-drug interaction; Hibiscus sabdariffa; human; pharmacokinetics

Artikel in diesem Heft

  1. Minireview
  2. Clinical assessment of arthritic knee pain by infrared thermography
  3. Original Articles
  4. Methanol stem bark extract of Adansonia digitata ameliorates chronic unpredictable mild stress-induced depression-like behavior: Involvement of the HPA axis, BDNF, and stress biomarkers pathways
  5. The protective effect of aqueous extract of Typha capensis rhizomes on cadmium-induced infertility in rats
  6. The aqueous and methanol extracts of Bambusa vulgaris (Poaceae) improve calcium and phosphorus levels, and bone microstructure in ovariectomized model of osteoporosis
  7. Assessment of epigenetic changes and oxidative DNA damage in rat pups exposed to polychlorinated biphenyls and the protective effect of curcumin in the prenatal period
  8. Assessment of heart rate variability for different somatotype category among adolescents
  9. Neuroprotective role of 6-Gingerol-rich fraction of Zingiber officinale (Ginger) against acrylonitrile-induced neurotoxicity in male Wistar rats
  10. Antioxidant activity of crude ethanolic extract and fractions of Ziziphus mauritiana Lam. (Rhamnaceae) leaves from Burkina Faso
  11. In vitro modulation of cytochrome P450 isozymes and pharmacokinetics of caffeine by extracts of Hibiscus sabdariffa Linn calyx
  12. Experimental hypogonadism: insulin resistance, biochemical changes and effect of testosterone substitution
  13. Accelerated wound healing process in rat by probiotic Lactobacillus reuteri derived ointment
  14. Evaluation of inductive effects of different concentrations of cyclosporine A on MMP-1, MMP-2, MMP-3, TIMP-1, and TIMP-2 in fetal and adult human gingival fibroblasts
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