ArticleBMC complementary and alternative medicine2019
Critical pharmacokinetic and pharmacodynamic drug-herb interactions in rats between warfarin and pomegranate peel or guava leaves extracts.
Article in BMC complementary and alternative medicine, 2019. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 12 papers.
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Who cites it
12 citing papers in PubMed, 36 citations in OpenAlex.
- Model-Based Evaluation of the Warfarin-Sulfamethoxazole Drug-Drug Interaction.European journal of drug metabolism and pharmacokinetics · 2026Article
- A reproducible rat model for warfarin studies: Prothrombin time assessment with minimal blood using the CoaguChek XS and determination of an effective warfarin dosage.Veterinarni medicina · 2026Article
- The Effect of Spinach (Journal of blood medicine · 2025Article
- Antidepressant- and Anxiolytic-like Effects of Pomegranate: Is It Acting by Common or Well-Known Mechanisms of Action?Plants (Basel, Switzerland) · 2024Review
- A comprehensive survey of warfarin-induced hepatic toxicity using histopathological, biomarker, and molecular evaluation.Heliyon · 2024Article
- Safety Issues of Herb-Warfarin Interactions.Current drug metabolism · 2024Review
- Impact of Pomegranate Juice on the Pharmacokinetics of CYP3A4- and CYP2C9-Mediated Drugs Metabolism: A Preclinical and Clinical Review.Molecules (Basel, Switzerland) · 2023Review
- Potential profound fluctuation in tacrolimus concentration on consumption of pomegranate rind extract: A Pharmacokinetic Experiment.Frontiers in pharmacology · 2023Article
- Effects of naringenin on the pharmacokinetics of tofacitinib in rats.Pharmaceutical biology · 2020Article
- Strong and Selective Inhibitory Effects of the Biflavonoid Selamariscina A against CYP2C8 and CYP2C9 Enzyme Activities in Human Liver Microsomes.Pharmaceutics · 2020Article
- Effect of You-Gui Yin on the Activities of Seven Cytochrome P450 Isozymes in Rats.Evidence-based complementary and alternative medicine : eCAM · 2020Article
- Current trends in drug metabolism and pharmacokinetics.Acta pharmaceutica Sinica. B · 2019Review
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Authors and funding
6 authors at 1 institution in 1 country.
Funding
Abstract
backgroundIn-depth information of potential drug-herb interactions between warfarin and herbal compounds with suspected anticoagulant blood thinning effects is needed to raise caution of concomitant administration. The current study aimed to investigate the impact of co-administration of pomegranate peel and guava leaves extracts, including their quality markers namely; ellagic acid and quercetin, respectively, on warfarin's in vivo dynamic activity and pharmacokinetic actions, in addition to potential in vitro cytochrome P450 enzymes (CYP) inhibition.
methodsInfluence of mentioned extracts and their key constituents on warfarin pharmacodynamic and kinetic actions and CYP activity were evaluated. The pharmacodynamic interactions were studied in Sprague Dawley rats through prothrombin time (PT) and International Normalized Ratio (INR) measurements, while pharmacokinetic interactions were detected in vivo using a validated HPLC method. Furthermore, potential involvement in CYP inhibition was also investigated in vitro on isolated primary rat hepatocytes.
resultsPreparations of pomegranate peel guava leaf extract, ellagic acid and quercetin in combination with warfarin were found to exert further significant increase on PT and INR values (p < 0.01) than when used alone (p < 0.05). Pomegranate peel extract showed insignificant effects on warfarin pharmacokinetics (p > 0.05), however, its constituent, namely, ellagic acid significantly increased warfarin C
conclusionAll combinations enhanced the anticoagulant activity of warfarin as the results of in vivo and in vitro studies were consistent. The current investigation confirmed serious drug herb interactions between warfarin and pomegranate peel or guava leaf extracts. Such results might conclude a high risk of bleeding from the co-administration of the investigated herbal drugs with warfarin therapy. In addition, the results raise attention to the blood-thinning effects of pomegranate peel and guava leaves when used alone.
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