Effect of Oral Administration of Valerian Extract at Different Doses on Pharmacokinetic Parameters of Carbamazepine in Rabbits
Keywords:Carbamazepine, CYP3A4, Valerian, Herb-drug interaction Pharmacokinetic parameters.
Carbamazepine (CBZ) is a narrow therapeutic index drug used in the treatment of trigeminal neuralgia and psychiatric disorders. Valerian (VAL) is a popular herbal product which should be prescribed to treat insomnia and anxiety. The study was designed to investigate the presence of significant pharmacokinetic (PK) interaction between Valerian (VAL) at different concentrations on Carbamazepine (CBZ) pharmacokinetic parameters in healthy male rabbits. In an in vivo, parallel-randomized controlled trial, the rabbits in three groups "first (control), second and third" were given oral doses of CBZ (50 mg/kg), for "second and third" groups (as test groups) rabbits were given (20 and 40 mg/kg/day) of the VAL respectively, as suspension in normal saline for eight consecutive days. On the eighth day, CBZ was co-administered an hour after adding the last dose of VAL suspension. Venous blood samples (1.0-1.5 mL) were obtained from rabbits' ears' marginal vein at predetermined different periods. The plasma of this blood separation was done using centrifugation and stored at -80°C, prior to analysis by using CBZ chemiluminescent enzyme immunoassay detection kit. Different PK parameters such as Cmax, tmax, t½, ke, AUC0-24 and AUC0-∞ were determined for the three groups, applying Statistical testing (ANOVA). The results showed statistical insignificant differences for all PK parameters among the three groups with (p˃0.05). The findings showed that VAL at both concentrations is not likely to interfere with PK parameters related to CBZ, Further confirmation in humans shoud be done before these findings are applied to patient care.
Fugh-Berman A. Herb-drug interactions. Lancet. 2000; 355(9198):134-138.
Chavez ML, Jordan MA, Chavez PI. Evidence-based drug-herbal interactions. Life Sci. 2006;78(18):2146-2157.
Nolan SJ, Marson AG, Weston J, Tudur SC. Carbamazepine versus phenobarbitone monotherapy for epilepsy: an individual participant data review. Cochrane Data base Syst Rev. 2015;23(7):CD001904.
Viktoriia B, Galia Z, Sidika S, Pham G, Vladimir Z, Martin R. Tissue-specific expression and activity of cytochrome P450 1A and 3A in rainbow trout (Oncorhynchus mykiss). Toxicology Letters. 2021;341:1-10.
Kane GC, Lipsky JJ. Drug-grapefruit juice interactions, Mayo Clinic Proceedings. 2000;75(9):933–942.
Ekor M. The growing use of herbal medicines: issues relating to adverse reactions and challenges in monitoring safety. Front Pharmacol. 2014;4:177.
Chen L, Chen Y, Chou M, Lin M, Yang L, Yen K. Pharmacokinetic Interactions between Carbamazepine and the Traditional Chinese Medicine Paeoniae Radix. Biol. Pharm. Bull. 2002;25(4):532-535.
Bibi Z. Role of cytochrome P450 in drug interactions. Nutrition & metabolism 2008;5:27.
Houghton PJ. The scientific basis for the reputed activity of valerian. Journal of Pharmacy and Pharmacology. 1999;51:505-512.
Krystal AD, Ressler I. The use of valerian in neuropsychiatry. CNS Spectrums. 2001;6:841-847.
Fong SYK., Gao Q, Zuo Z. Interaction of carbamazepine with herbs, dietary supplements, and food: A systematic review. Evidence-Based Complementary and Alternative Medicine. 2013;2013:898261.
Patsalos PN, Perucca E. Clinically important drug interactions in epilepsy: general features and interactions between antiepileptic drugs. Lancet Neurol. 2003;2(6): 347-356.
Tang J, Song X, Zhu M. Study on the pharmacokinetics drug-drug interaction potential of Glycyrrhiza uralensis, a traditional Chinese medicine, with lidocaine in rats. Phytother. Res. 2009;23:603–607.
Parasuraman S, Raveendran R, Kesavan R. Blood sample collection in small laboratory animals. Journal of Pharmacology and Pharmacotherapeutics. 2010; 1(2):87–93.
Svein I, Johannessen Cecilie JL. Antiepileptic Drug Interactions-Principles and Clinical Implications. Current Neuropharmacology. 2010;8:254-267.
Landmark CJ, Patsalos PN. Interactions between antiepileptic drugs and herbal medicines. Bol Latinoam Caribe Plant Med. 2008;7:109–118.
Mohamed MF, Frye RF. Effects of herbal supplements on drug glucuronidation. Review of clinical, animal and in vitro studies. Planta Medica. 2011;77(4):311–321.
Thabrew I, Munasinghe J, Chackrewarthi S, Senarath S. The effects of Cassia auriculata and Cardiospermum halicacabum teas on the steady state blood level and toxicity of carbamazepine. Journal of Ethnopharmacology. 2004;90(1):145–150.
Pattanaik S, Hota D, Prabhakar S, Kharbanda P, Pandhi P. Pharmacokinetic interaction of single dose of piperine with steady-state carbamazepine in epilepsy patients. Phytotherapy Research. 2009;23(9):1281–1286.
Liu P., Wei L. Effect of Platycodon grandiflorum on the blood concentration of carbamazepine in rabbits. Evaluation and Analysis of Drug-Use in Hospitals of China. 2008;8(5):366-369.
Chi YC, Lin SP, Hou YC. A new herb-drug interaction of Polygonum cuspidatum, a resveratrol-rich nutraceutical, with carbamazepine in rats. Toxicology and Applied Pharmacology. 2012;263(3):315–322.
Chandra RH, Rajkumar M, Veeresham C. Pharmacokinetic interaction of ginkgo biloba with carbamazepine. Planta Medica. 2009;(4):454.
Zhang ZJ, Kang WH, Li Q, Tan Q. The beneficial effects of the herbal medicine free and easy wanderer plus (FEWP) for mood disorders: double-blind, placebo-controlled studies. Journal of Psychiatric Research. 2007;41(10):828–836.
Li W, Tan Q, Zhang Z. Randomized double-blind controlled clinical trial of the combination of Xiao-yao-san and carbamazepine in the treatment of bipolar disorders. Zhong Guo Lin Chuang Yao Li Xue Za Zhi. 2005;21:336–340.
Qiu W, Jiang XH, Liu CX, Ju Y, Jin JX. Effect of Berberine on the Pharmacokinetics of Substrates of CYP3A and P-gp. Phytother. Res. 2009;23:1553–1558.
Ohnishi N, Nakasako S, Okada k, Umehara S, Takara k, Nagasawa k. et al. Interactions between Traditional Herbal and Western Medicines. Lack of Pharmacokinetic Interactions between Saiko-ka-ryukotsu-borei-to and Carbamazepine in Rats. European Journal of Drug Metabolism and Pharmacokinetics. 2001;26(1, 2):129-135.
Burstein A, Horton R, Dunn T, Alfaro R, Piscitelli S, Theodore W. Lack of effect of St John’s Wort on carbamazepine pharmacokinetics in healthy volunteers. Clin. Pharmacol Ther. 2000;68:605-612.
Abushammala IM, El-Shaikh Ali FK, Abu Shammaleh KF, Taha MM, Miqdad MY. Effect of Panax ginseng on Carbamazepine Pharmacokinetics in Rabbits. Turk J Pharm Sci. 2021;25:18(1):17-20.
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