Interaction of Warfarin with Herbs Based on Pharmacokinetic and Pharmacodynamic Parameters

Warfarin is an oral anticoagulant that has been widely used and has strong efficacy, but the use of warfarin is still a concern because of its narrow therapeutic index which cause interactions when co-administration with drugs, herbs or food. This interaction can affect the pharmacokinetics and pharmacodynamics of warfarin and the most fatal effect from warfarin interactions is bleeding. In this review article data on warfarin-herbs interactions were collected based on pharmacokinetic parameters (AUC0-∞, Cmax, T1/2, Cl/F, and V/F), while pharmacodynamic parameters (International normalized ratio (INR), platelet aggregation, AUC INR and Protombine Time). As a result some herbs had significant interactions with warfarin. Herbs that affect warfarin pharmacokinetic were Danshen gegen, echinacea, St. John's wort and caffeine and herbs that affect pharmacodynamic were policosanol, Ginkgo biloba, cranberry, St. John's wort, ginseng, pomegranate, Psidium guajava and curcumin, so co-administration warfarin with herbs need to be considered.Keywords: Warfarin, Interactions, Herbs, Pharmacokinetics, Pharmacodynamics

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Bidirectional Influences of Cranberry on the Pharmacokinetics and Pharmacodynamics of Warfarin with Mechanism Elucidation

Nutrients ◽

10.3390/nu13093219 ◽

2021 ◽

Vol 13 (9) ◽

pp. 3219

Author(s):

Chung-Ping Yu ◽

Meng-Syuan Yang ◽

Pei-Wen Hsu ◽

Shiuan-Pey Lin ◽

Yu-Chi Hou

Keyword(s):

Breast Cancer Resistance Protein ◽

Plasma Concentrations ◽

Therapeutic Index ◽

Cancer Resistance ◽

Pharmacokinetics And Pharmacodynamics ◽

Narrow Therapeutic Index ◽

Combined Use ◽

Ingestion Time ◽

Resistance Protein ◽

Metabolizing Enzyme

Cranberry is a dietary supplement popularly used for the prophylaxis of urinary tract infection. Interestingly, cranberry–warfarin interactions in clinical reports have shown bidirectional outcomes. (±) Warfarin, a widely prescribed anticoagulant, but with a narrow therapeutic index, contains equal amounts of S- and R-warfarin, of which S-warfarin is more active. The aim of this study was to investigate the effects of different ingestion times of cranberry on the pharmacokinetics and pharmacodynamics of warfarin. Rats were orally administered (±) warfarin (0.2 mg/kg) with and without cranberry (5.0 g/kg) at 0.5 h prior to the warfarin, and at 10 h after the warfarin. The plasma concentrations of S- and R-warfarin were determined by LC/MS. The results indicate that cranberry ingested at 0.5 h before (±) warfarin significantly decreased the systemic exposures of S-warfarin and R-warfarin. Conversely, when cranberry was ingested at 10 h after (±) warfarin, the elimination of S-warfarin was significantly inhibited, and the anticoagulation effect of (±) warfarin was significantly enhanced. The results of the mechanism studies indicate that cranberry activated the breast cancer resistance protein (BCRP), which mediated the efflux transports of S-warfarin and R-warfarin. Moreover, the metabolites of cranberry inhibited cytochrome P450 (CYP) 2C9, the main metabolizing enzyme for S-warfarin. In conclusion, cranberry affected the pharmacokinetics of (±) warfarin in a bidirectional manner by activating the BCRP by CJ during absorption and inhibiting the BCRP and CYP2C9 by CMs during elimination, depending on the ingestion time of CJ. The combined use of cranberry with warfarin should be avoided.

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Genetic-based dosing in orthopedic patients beginning warfarin therapy

Blood ◽

10.1182/blood-2007-01-069609 ◽

2007 ◽

Vol 110 (5) ◽

pp. 1511-1515 ◽

Cited By ~ 134

Author(s):

Eric A. Millican ◽

Petra A. Lenzini ◽

Paul E. Milligan ◽

Leonard Grosso ◽

Charles Eby ◽

...

Keyword(s):

Warfarin Therapy ◽

Smoking Status ◽

Warfarin Dose ◽

Therapeutic Index ◽

International Normalized Ratio ◽

Narrow Therapeutic Index ◽

Therapy Initiation ◽

Estimated Blood Loss ◽

Epoxide Reductase ◽

Orthopedic Patients

AbstractHigh variability in drug response and a narrow therapeutic index complicate warfarin therapy initiation. No existing algorithm provides recommendations on refining the initial warfarin dose based on genetic variables, clinical data, and international normalized ratio (INR) values. Our goal was to develop such an algorithm. We studied 92 patients undergoing primary or revision total hip or knee replacement. From each patient we collected a blood sample, clinical variables, current medications, and preoperative and postoperative laboratory values. We genotyped for polymorphisms in the cytochrome P450 (CYP) 2C9 and vitamin K epoxide reductase (VKORC1) genes. Using stepwise regression, we developed a model for refining the warfarin dose after the third warfarin dose. The algorithm explained four fifths of the variability in therapeutic dose (R2adj of 79%). Significant (P > .05) predictors were INR value after 3 doses (47% reduction per 0.25-unit rise), first warfarin dose (+7% per 1 mg), CYP2C9*3 and CYP2C9*2 genotype (−38% and −17% per allele), estimated blood loss (interacting with INR3), smoking status (+20% in current smokers), and VKORC1 (−11% per copy of haplotype A). If validated, this model should provide a safer, more effective process for initiating warfarin therapy.

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Effects of St John's wort and CYP2C9 genotype on the pharmacokinetics and pharmacodynamics of gliclazide

British Journal of Pharmacology ◽

10.1038/sj.bjp.0707685 ◽

2008 ◽

Vol 153 (7) ◽

pp. 1579-1586 ◽

Cited By ~ 58

Author(s):

H Xu ◽

K M Williams ◽

W S Liauw ◽

M Murray ◽

R O Day ◽

...

Keyword(s):

Pharmacokinetics And Pharmacodynamics ◽

Cyp2c9 Genotype ◽

St John’S Wort ◽

St John's Wort

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Effects of Hypericum perforatum (St John's wort) on the pharmacokinetics and pharmacodynamics of rivaroxaban in humans

British Journal of Clinical Pharmacology ◽

10.1111/bcp.14553 ◽

2020 ◽

Author(s):

Irene Scholz ◽

Evangelia Liakoni ◽

Felix Hammann ◽

Katharina Elisabeth Grafinger ◽

Urs Duthaler ◽

...

Keyword(s):

Hypericum Perforatum ◽

Pharmacokinetics And Pharmacodynamics ◽

St John’S Wort ◽

St John's Wort

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Ginger Significantly Decreased the Oral Bioavailability of Cyclosporine in Rats

The American Journal of Chinese Medicine ◽

10.1142/s0192415x06004338 ◽

2006 ◽

Vol 34 (05) ◽

pp. 845-855 ◽

Cited By ~ 17

Author(s):

Hsiu-Mei Chiang ◽

Pei-Dawn Lee Chao ◽

Su-Lan Hsiu ◽

Kuo-Ching Wen ◽

Shang-Yuan Tsai ◽

...

Keyword(s):

Oral Bioavailability ◽

Therapeutic Index ◽

Zingiber Officinale ◽

Compartment Model ◽

Pharmacokinetic Parameters ◽

Fluorescence Polarization Immunoassay ◽

Crossover Designs ◽

Narrow Therapeutic Index ◽

Blood Samples ◽

Zingiber Officinale Roscoe

Ginger (roots of Zingiber officinale ROSCOE) is a popular spice and herbal medicine worldwide. Cyclosporine is clinically used as an important immunosupressant with narrow therapeutic index. This study attempted to investigate the effect of ginger juice on the pharmacokinetics of cyclosporine in rats. Rats were orally administered cyclosporine alone and in combination with ginger juice (5 ml/kg) concomitantly, as well as 2 hours after the ginger juice, respectively, in crossover designs. In addition, rats were intravenously administered cyclosporine with and without an oral dose of ginger juice (5 ml/kg). The blood samples were withdrawn via cardiopuncture at determined time points and cyclosporine concentrations were determined by a specific monoclonal fluorescence polarization immunoassay. The pharmacokinetic parameters of cyclosporine were calculated using a non-compartment model of WINNONLIN. The results indicated that concomitant intake of ginger significantly decreased Cmaxand AUC0–tof oral cyclosporine by 70.9% and 63.1%, respectively. The intake of ginger 2 hours before cyclosporine significantly decreased Cmaxand AUC0–tby 51.4% and 40.3%, respectively. In contrast, the pharmacokinetics of intravenous cyclosporine not altered by orally in combination with ginger juice. In conclusion, ginger significantly decreased the oral bioavailability of cyclosporine, and the interaction should occur at the absorption phase. Patients treated with cyclosporine should be discouraged from using ginger products to ensure the efficacy of cyclosporine.

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Effect of St. John's Wort on The Pharmacokinetics and Pharmacodynamics of Quazepam

Clinical Pharmacology & Therapeutics ◽

10.1016/s0009-9236(03)90518-2 ◽

2003 ◽

Vol 73 (2) ◽

pp. P44-P44 ◽

Cited By ~ 2

Author(s):

A. Kawaguchi ◽

M. Ohmori ◽

S. Tsuruoka ◽

K. Harada ◽

A. Fujimura

Keyword(s):

Pharmacokinetics And Pharmacodynamics ◽

St John’S Wort ◽

St John's Wort

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Therapeutic Drug Monitoring of Cytotoxic Drugs

International Journal of Drug Delivery Technology ◽

10.25258/ijddt.10.2.16 ◽

2020 ◽

Vol 10 (02) ◽

pp. 284-291

Author(s):

Qutaiba Ahmad Al Khames Aga ◽

Yazan A. Bataineh ◽

Hala Mousa Sbaih

Keyword(s):

Therapeutic Drug Monitoring ◽

Drug Monitoring ◽

Malignant Tumors ◽

Therapeutic Index ◽

Review Article ◽

Cytotoxic Drugs ◽

Therapeutic Drug ◽

Narrow Therapeutic Index ◽

Time Curve ◽

The Common

The majority of anticancer drugs are recognized with a narrow therapeutic index, the area under the plasma levels vs. time curve (AUC) is the common pharmacokinetic (PK) parameter, which utilizes specifically for cytotoxic drugs. Therapeutic drug monitoring (TDM) approach in these drugs has never been completely applied due to different reasons, for example, the use of combination chemotherapies for different malignant tumors, and the behavior of intracellular compounds; it is possible to eliminate these limitations by using specific concentrations of cytotoxic drugs and measure AUC after certain conditions. In this review article, we discussed the common TDM parameters, methods of analysis, and some of drug interactions for a group of cytotoxic drugs.

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Interactions between Antidepressants and Warfarin: A Review

Current Psychiatry Research and Reviews ◽

10.2174/2666082216999200622135657 ◽

2021 ◽

Vol 16 (3) ◽

pp. 194-204

Author(s):

Sukru Alperen Korkmaz ◽

Tekin Guney ◽

Imdat Dilek ◽

Ali Caykoylu

Keyword(s):

Systematic Review ◽

Interaction Potential ◽

Empirical Data ◽

Therapeutic Index ◽

International Normalized Ratio ◽

Google Scholar ◽

Narrow Therapeutic Index ◽

Hand Search ◽

Risk Of Bleeding ◽

Sufficient Knowledge

Background: Since warfarin has a very narrow therapeutic index, the interaction between warfarin and antidepressants is very critical and has potentially severe consequences. It is unclear whether clinicians have sufficient knowledge about the risk of bleeding when warfarin and antidepressants are used concomitantly. Objective: In this systematic review, we discuss the main considerations when using warfarin with antidepressants. Methods: The information about warfarin-antidepressant interactions was obtained from Google Scholar®, PubMed/MEDLINE® and a hand search of the published literature. The following research terms which were systematically combined with each other to find articles: warfarin, anticoagulant, interactions, antidepressant (and each antidepressant name individually), SSRI, SNRI, TCA, MAOI. Results: Several possible mechanisms that can cause bleeding when antidepressants and warfarin are used concomitantly, have been discussed. According to the available data, sertraline and citalopram/ escitalopram are safer antidepressants to use with warfarin, whereas fluoxetine and fluvoxamine have a higher interaction potential with warfarin. The remaining antidepressants appear to lie somewhere in between and have little empirical data to guide the clinicians. Conclusion: It is recommended that when an antidepressant is prescribed to a patient using warfarin, patient’s international normalized ratio (INR) level should be checked regularly. In this review, the interaction between warfarin and antidepressants, including new ones, were evaluated inclusively and in detail.

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