The Effect of Spinach (Amaranthus hybridus) on the Pharmacokinetic and Pharmacodynamic Profile of Warfarin in New Zealand White Rabbits

Norisca Aliza Putriana,1 Taofik Rusdiana,1 Tina Rostinawati,2 Irma Rahayu Latarissa3 1Department of Pharmaceuticals and Pharmaceutical Technology, Faculty of Pharmacy, Universitas Padjadjaran, Sumedang, Indonesia; 2Department of Biology Pharmacy, Faculty of Pharmacy, Universitas Padjadjaran, Sumedan...

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Main Authors: Putriana NA, Rusdiana T, Rostinawati T, Latarissa IR
Format: Article
Language:English
Published: Dove Medical Press 2025-02-01
Series:Journal of Blood Medicine
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Online Access:https://www.dovepress.com/the-effect-of-spinach-amaranthus-hybridus-on-the-pharmacokinetic-and-p-peer-reviewed-fulltext-article-JBM
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author Putriana NA
Rusdiana T
Rostinawati T
Latarissa IR
author_facet Putriana NA
Rusdiana T
Rostinawati T
Latarissa IR
author_sort Putriana NA
collection DOAJ
description Norisca Aliza Putriana,1 Taofik Rusdiana,1 Tina Rostinawati,2 Irma Rahayu Latarissa3 1Department of Pharmaceuticals and Pharmaceutical Technology, Faculty of Pharmacy, Universitas Padjadjaran, Sumedang, Indonesia; 2Department of Biology Pharmacy, Faculty of Pharmacy, Universitas Padjadjaran, Sumedang, Indonesia; 3Department of Pharmacology and Clinical Pharmacy, Faculty of Pharmacy, Universitas Padjadjaran, Sumedang, IndonesiaCorrespondence: Norisca Aliza Putriana, Department of Pharmaceuticals and Pharmaceutical Technology, Faculty of Pharmacy, Universitas Padjadjaran, Jl. Raya Bandung Sumedang KM. 21, Jatinangor, West Java, 45363, Indonesia, Email norisca@unpad.ac.idIntroductions: Spinach (Amaranthus hybridus) is a green vegetable containing 380 μg/100 g of vitamin K, while warfarin serves as an antagonist in inhibiting vitamin K epoxide reductase subunit C1 (VKORC). In this context, the co-administration of warfarin and spinach is frequently encountered among Indonesian patients, potentially leading to drug-food interactions. This study aimed to investigate the effect of concomitant administration of spinach on the pharmacokinetic and pharmacodynamic profile of warfarin in New Zealand White rabbits.Methods: A total of 24 New Zealand White rabbits weighing about 1.5– 2 kg were used in this study. For 16 days, these rabbits were given oral warfarin at a dose of 0.4 mg/kg BW by 10.00 am. Subsequently, 3 mL of blood samples were withdrawn in the lateral vein of the ear on the 13th and 16th days. The Prothrombin Time-International Normalized Ratio (PT-INR) is used to evaluate the pharmacodynamic profile, while the plasma concentration of S(R)-warfarin (Cp (AV)), half-life (t&half;), area under the curve (AUC), volume of distribution (Vd), and clearance (CL) are analyzed to determine the pharmacokinetic effects of warfarin.Results: In the Fluconazole (FZ) group, there was a significant increase in the area under the curve (AUC) at maximum concentration (Cmax) after treatment, with a p-value of < 0.05. In the Amaranthus hybridus dose 1 (AH-1) and Amaranthus hybridus dose 2 (AH-2) groups, AUC and plasma drug concentration (Cp (AV)) were higher after treatment but the results of statistical analysis were not significant.Conclusion: There was no pharmacokinetic or pharmacodynamic interaction between spinach (Amaranthus hybridus) and warfarin. Additionally, patients subjected to warfarin therapy could consume spinach with a recommended portion size below 100 grams per day.Keywords: spinach, warfarin, vitamin K, New Zealand White rabbits, area under curve
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spelling doaj-art-7fd40dd370dd4bd4aa575f6ec1c154e92025-08-20T02:13:23ZengDove Medical PressJournal of Blood Medicine1179-27362025-02-01Volume 167582100263The Effect of Spinach (Amaranthus hybridus) on the Pharmacokinetic and Pharmacodynamic Profile of Warfarin in New Zealand White RabbitsPutriana NARusdiana TRostinawati TLatarissa IRNorisca Aliza Putriana,1 Taofik Rusdiana,1 Tina Rostinawati,2 Irma Rahayu Latarissa3 1Department of Pharmaceuticals and Pharmaceutical Technology, Faculty of Pharmacy, Universitas Padjadjaran, Sumedang, Indonesia; 2Department of Biology Pharmacy, Faculty of Pharmacy, Universitas Padjadjaran, Sumedang, Indonesia; 3Department of Pharmacology and Clinical Pharmacy, Faculty of Pharmacy, Universitas Padjadjaran, Sumedang, IndonesiaCorrespondence: Norisca Aliza Putriana, Department of Pharmaceuticals and Pharmaceutical Technology, Faculty of Pharmacy, Universitas Padjadjaran, Jl. Raya Bandung Sumedang KM. 21, Jatinangor, West Java, 45363, Indonesia, Email norisca@unpad.ac.idIntroductions: Spinach (Amaranthus hybridus) is a green vegetable containing 380 μg/100 g of vitamin K, while warfarin serves as an antagonist in inhibiting vitamin K epoxide reductase subunit C1 (VKORC). In this context, the co-administration of warfarin and spinach is frequently encountered among Indonesian patients, potentially leading to drug-food interactions. This study aimed to investigate the effect of concomitant administration of spinach on the pharmacokinetic and pharmacodynamic profile of warfarin in New Zealand White rabbits.Methods: A total of 24 New Zealand White rabbits weighing about 1.5– 2 kg were used in this study. For 16 days, these rabbits were given oral warfarin at a dose of 0.4 mg/kg BW by 10.00 am. Subsequently, 3 mL of blood samples were withdrawn in the lateral vein of the ear on the 13th and 16th days. The Prothrombin Time-International Normalized Ratio (PT-INR) is used to evaluate the pharmacodynamic profile, while the plasma concentration of S(R)-warfarin (Cp (AV)), half-life (t&half;), area under the curve (AUC), volume of distribution (Vd), and clearance (CL) are analyzed to determine the pharmacokinetic effects of warfarin.Results: In the Fluconazole (FZ) group, there was a significant increase in the area under the curve (AUC) at maximum concentration (Cmax) after treatment, with a p-value of < 0.05. In the Amaranthus hybridus dose 1 (AH-1) and Amaranthus hybridus dose 2 (AH-2) groups, AUC and plasma drug concentration (Cp (AV)) were higher after treatment but the results of statistical analysis were not significant.Conclusion: There was no pharmacokinetic or pharmacodynamic interaction between spinach (Amaranthus hybridus) and warfarin. Additionally, patients subjected to warfarin therapy could consume spinach with a recommended portion size below 100 grams per day.Keywords: spinach, warfarin, vitamin K, New Zealand White rabbits, area under curvehttps://www.dovepress.com/the-effect-of-spinach-amaranthus-hybridus-on-the-pharmacokinetic-and-p-peer-reviewed-fulltext-article-JBMspinachwarfarinvitamin knew zealand white rabbitsarea under curve
spellingShingle Putriana NA
Rusdiana T
Rostinawati T
Latarissa IR
The Effect of Spinach (Amaranthus hybridus) on the Pharmacokinetic and Pharmacodynamic Profile of Warfarin in New Zealand White Rabbits
Journal of Blood Medicine
spinach
warfarin
vitamin k
new zealand white rabbits
area under curve
title The Effect of Spinach (Amaranthus hybridus) on the Pharmacokinetic and Pharmacodynamic Profile of Warfarin in New Zealand White Rabbits
title_full The Effect of Spinach (Amaranthus hybridus) on the Pharmacokinetic and Pharmacodynamic Profile of Warfarin in New Zealand White Rabbits
title_fullStr The Effect of Spinach (Amaranthus hybridus) on the Pharmacokinetic and Pharmacodynamic Profile of Warfarin in New Zealand White Rabbits
title_full_unstemmed The Effect of Spinach (Amaranthus hybridus) on the Pharmacokinetic and Pharmacodynamic Profile of Warfarin in New Zealand White Rabbits
title_short The Effect of Spinach (Amaranthus hybridus) on the Pharmacokinetic and Pharmacodynamic Profile of Warfarin in New Zealand White Rabbits
title_sort effect of spinach amaranthus hybridus on the pharmacokinetic and pharmacodynamic profile of warfarin in new zealand white rabbits
topic spinach
warfarin
vitamin k
new zealand white rabbits
area under curve
url https://www.dovepress.com/the-effect-of-spinach-amaranthus-hybridus-on-the-pharmacokinetic-and-p-peer-reviewed-fulltext-article-JBM
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