LIQUORICE BEVERAGE EFFECT ON THE PHARMACOKINETIC PARAMETERS OF ATORVASTATIN, SIMVASTATIN, AND LOVASTATIN BY LIQUID CHROMATOGRAPHY-MASS SPECTROSCOPY/MASS SPECTROSCOPY
Objective: The objective of this study is to examine the effects of pre-consumption of freshly prepared liquorice beverage (4 ml/kg) on the
pharmacokinetic (PK) parameters of (80 mg/kg) oral dose of atorvastatin, simvastatin, and lovastatin in healthy rats plasma.
Methods: A simple, rapid, and applicable analytical method was developed for the determination of each statin in rats' plasma. This method uses
liquid chromatography-mass spectroscopy/mass spectroscopy. The mobile phase composed of methanol and formic acid in water and glimepiride as
an internal standard. 108 rats were used in this study. Liquorice juice was given, and then each of the statins was given to test groups and liquorice
only to the control groups, and then plasma samples were withdrawn on specific time schedule then PK analysis was performed.
Results: The analytical method showed acceptable linearity, recovery, precision, and accuracy. Administration of liquorice resulted in a significant
increase in maximum concentration in plasma (C
) of the three statins, also the area under plasma level-time curves (area under curve) was increased
significantly. Moreover, the bioavailability of the drugs. On the other hand, the elimination of the three drugs showed no great changes, which suggests
an interaction between liquorice and the transporting system of statins on the gut and biliary wall.
Conclusion: Consumption of liquorice results in increase bioavailability of atorvastatin, simvastatin, and lovastatin.
Keywords: Liquorice, Atorvastatin, Liquid chromatography-mass spectroscopy/mass spectroscopy, Simvastatin, Lovastatin, Pharmacokinetic
Alshehri MM. A validated capillary electrophoresis method for
simultaneous determination of ezetimibe and atorvastatin in
pharmaceutical formulations. Saudi Pharm J 2012;20(2):143-8.
Stancu C, Sima A. Statins: Mechanism of action and effects. J Cell Mol
Goldberg A, Hopkins P, Toth P, Ballantyne C, Rader D, Robinson J, et al.
Familial hypercholesterolemia: Screening, diagnosis and management
of pediatric and adult patients: Clinical guidance from the National
Lipid Association Expert Panel on Familial Hypercholesterolemia.
J Clin Lipidol 2011;5(3):1-8.
Khan FN, Dehghan MH. Enhanced bioavailability of atorvastatin
calcium from stabilized gastric resident formulation. AAPS
Qinna NA, Kamona BS, Alhussainy TM, Taha H, Badwan AA,
Matalka KZ. Effects of prickly pear dried leaves, artichoke leaves,
turmeric and garlic extracts, and their combinations on preventing
dyslipidemia in rats. ISRN Pharmacol 2012;2012:167979.
Braamskamp M, Wijburg F, Wiegman A. Drug therapy of
hypercholesterolaemia in children and adolescent. Drugs
Whirl-Carrillo M, McDonagh EM, Hebert JM, Gong L, Sangkuhl K,
Thorn CF, et al. Pharmacogenomics knowledge for personalized
medicine. Clin Pharmacol Ther 2012;92(4):414-7.
LennernÃ¤s H. Clinical pharmacokinetics of atorvastatin. Clin
Mauro VF. Clinical pharmacokinetics and practical applications of
simvastatin. Clin Pharmacokinet 1993;24(3):195-202.
Kantola T, KivistÃ¶ KT, Neuvonen PJ. Grapefruit juice greatly increases
serum concentrations of lovastatin and lovastatin acid. Clin Pharmacol
Genser D. Food and drug interaction: Consequences for the nutrition/
health status. Ann Nutr Metab 2008;52 Suppl 1:29-32.
Tamimi L, Dayyih WA, Qinna N, Mallah E, Arafat T. Pioglitazone
levels and its pharmacokinetic application in presence of sucralose in
animals plasma, by HPLC method. Pharm Anal Acta 2014;5(9):318-25.
Le Goff-Klein N, Koffel JC, Jung L, Ubeaud G. In vitro inhibition of
simvastatin metabolism, a HMG-CoA reductase inhibitor in human and
rat liver by bergamottin, a component of grapefruit juice. Eur J Pharm
Tbeekh HT, Dayyih WA, Mallah E, Qinna N, Awad RM, Arafat TA.
Pomegranate juice effects on pharmacokinetic parameters of
metronidazole by using HPLC-MS. World J Pharm Pharm Sci
Siracusa L, Saija A, Cristani M, Cimino F, Dâ€™Arrigo M, Trombetta D,
et al. Phytocomplexes from liquorice (Glycyrrhiza glabra L.)
leaves â€“ Chemical characterization and evaluation of their
antioxidant, anti-genotoxic and anti-inflammatory activity. Fitoterapia
Obolentseva GV, Litvinenko VI, Ammosov AS, Popova TP,
Sampiev AM. Pharmacological and therapeutic properties of licorice
preparations (a review). Pharm Chem J 1999;33(24):31-7.
Fiore C, Eisenhut M, Ragazzi E, Zanchin G, Armanini D. A history
of the therapeutic use of liquorice in Europe. J Ethnopharmacol
Al-Deeb ID, Arafat TA, Irshaid YM. The effect of licorice drink on
the systemic exposure of verapamil in rabbits. Drug Metab Lett
Won CS, Oberlies NH, Paine MF. Mechanisms underlying food-
drug interactions: Inhibition of intestinal metabolism and transport.
Pharmacol Ther 2012;136(2):186-201.
Neuvonen PJ, Niemi M, Backman JT. Drug interactions with lipidlowering
drugs: Mechanisms and clinical
Dayyih WA, Al-Fayez A, Tamimi L, Mallah E, Arafat T. Simultaneous
determination of Atorvastatin, Glimepiride and Amlodipine in solution
and plasma matrix using HPLC/UV method. J Chem Pharm Res
Fukazawa I, Uchida N, Uchida E, Yasuhara H. Effects of grapefruit
juice on pharmacokinetics of atorvastatin and Simvastatin in Japanese.
Br J Clin Pharmacol 2004;57(4):448-5.
Code of Federal Regulation, Title 21, vol. 3. Available from: http:
www.accessdata.fda.gov. [Last accessed on 2015 Apr].
United State Pharmacopeia. Validation of compendial methods. US
Pharmacopial Convention. Ch. 1225. Rockville, MD: USP; 2010. p. 29.
Paine M, Khalighi M, Fisher J, Shen D, Kunze K, Mars C, et al.
Characterization of interintestinal and intraintestinal variations
in human CYP3A-dependent metabolism. J Pharmacol ExpTher
Paine S, Parker A, Gardiner P, Webborn P, Riley R. Prediction of the
pharmacokinetics of atorvastatin, cerivastatin, and indomethacin using
kinetic models applied to isolated rat hepatocytes. Drug Metab Dispos
Paine SW, Parker AJ, Gardiner P, Webborn PJ, Riley RJ. Prediction
of the pharmacokinetics of atorvastatin, cerivastatin, and indomethacin
using kinetic models applied to isolated rat hepatocytes. Drug Metab
Chouksey R, Pandey H, Jain AK, Soni H, Saraogi GK. Preparation
and evaluation of the self-emulsifying drug delivery system
containing atorvastatin HMG-COA inhibitors. Int J Pharm Pharm Sci
Kent UM, Aviram M, Rosenblat M, Hollenberg PF. The licorice root
derived isoflavan glabridin inhibits the activities of human cytochrome
P450S 3A4, 2B6, and 2C9. Drug Metab Dispos 2002;30(6):709-15.
Kuhn MA. Herbal remedies: Drug-herb interactions. Crit Care Nurse
Watanabe T, Kusuhara H, Maeda K, Kanamaru H, Saito Y, Hu Z, et al.
Investigation of the rate-determining process in the hepatic elimination
of HMG-CoA reductase inhibitors in rats and humans. Drug Metab
Idkaidek M, Najib N, Arafat T, Al-Ghazawi A. Population
Pharmacokinetics of Atorvastatin, simvastatin and Pravastatin after oral
administration in human. Saudi Pharm J 2008;16(1):82-4.
Omar HR, Komarova I, El-Ghonemi M, Fathy A, Rashad R,
Abdelmalak HD, et al. Licorice abuse: Time to send a warning message.
Ther Adv Endocrinol Metab 2012;3(4):125-38.
Lilja JJ, Neuvonen M, Neuvonen PJ. Effects of regular consumption
of grapefruit juice on the pharmacokinetics of simvastatin. Br J Clin
Wang X, Zhang H, Chen L, Shan L, Fan G, Gao X. Liquorice, a unique
guide drugâ€ of traditional Chinese medicine: A review of its role in
drug interactions. J Ethnopharmacol 2013;150(3):781-90.
Hou YC, Lin SP, Chao PD. Liquorice reduced cyclosporine
bioavailability by activating P-glycoprotein and CYP 3A. Food Chem
Tachjian A, Maria V, Jahangir A. Use of herbal products and potential
interactions in patients with cardiovascular diseases. J Am Coll Cardiol
Nowack R. Review article: Cytochrome P450 enzyme, and transport
protein mediated herb-drug interactions in renal transplant patients:
Grapefruit juice, St Johnâ€™s Wort - and beyond! Nephrology (Carlton)
Gunturu S. Drugâ€“nutrient interactions. In: Pitchumoni CS,
Dharmarajan T, editors. Geriatric Gastroenterology. New York:
Springer; 2012. p. 89-98.
Izzo AA. Interactions between herbs and conventional drugs: Overview
of the clinical data. Med Princ Pract 2012;21(5):404-28.
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