Ruzu herbal bitters altered the pharmacokinetic profile of metformin tablets in healthy Nigerian volunteers following concurrent administration
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Abstract
Background: Ruzu® Herbal bitters (RHB) is a commercial polyherbal formulation made from a blend of various parts and fruits of plant of Uvaria chamae P. Beauv., Curculigo pilosa Schumach. & Thonn and Citrullus colocynthis (L) Schrad. It is claimed to be used for the management of diabetes, cure weak erection in men, boost the immune system and effective against typhoid and malaria.
Objectives: This study was carried out to investigate the potential interactions between metformin tablets when co-administered with RHB.
Methods: A total of ten healthy volunteers were recruited and assigned into two groups. One group ingested 500 mg single dose metformin tablet orally using table water while the other group took 30 mL of the herbal formulation daily for 4 days, followed by 500 mg single oral dose of metformin tablet taken with same volume of the bitters on the fifth day. Blood samples were collected and analyzed using a validated High performance Liquid Chromatography.
Results: All the pharmacokinetic parameters evaluated were altered in the presence of RHB. The terminal half-life (t1/2, p = 0.01), apparent volume of distribution (Vd/F, p = 0.008), systemic clearance (Cl/F, p = 0.034) and mean residence time (MRT, p = 0.03) were reduced while terminal elimination rate constant (Kel, p = 0.005) was elevated with Ruzu herbal bitters. This influence is likely mediated by competitive inhibition or induction of the metformin transporters such as organic cation transporter-1(OCT-1), Plasma membrane monoamine transporter (PMAT) by the phytochemical constituents of RHB. The changes observed were statistically significant for the t1/2, Kel, Vd/F, Cl/F and MRT (p < 0.05).
Conclusion: The results obtained from the study showed that co-administration of metformin and RHB altered the pharmacokinetic parameters of Metformin.
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Oreagba IA, Oshikoya KA, Amachree M (2011). Herbal medicine use among urban residents in Lagos, Nigeria. BMC Complementary and
Alternative Medicine 11: 117. doi: 10.1186/1472-6882-11-117. PMID: 22117933; PMCID: PMC3252251. 84 West African Journal of Pharmacy (2023) 34 (2)
Awodele O, Amagon KI, Usman SO, Obasi PC (2014). Safety of herbal medicines use: case study of ikorodu residents in Lagos, Nigeria. Current Drug Safety 9(2): 138-44.
El Hajj M, Holst L (2020). Herbal Medicine Use During Pregnancy: A Review of the Literature with a Special Focus on Sub-Saharan Africa. Frontiers in Pharmacology 11, 866. doi: 10.3389/fphar.2020.00866.
Olisa NS, Oyelola FT (2009). Evaluation of use of herbal medicines among ambulatory hypertensive patients attending a secondary health care facility in Nigeria. International Journal of Pharmacy Practice 17(2): 101-5. PMID: 20214258.
Onyeka TC, Ezike HA, Nwoke OM, Onyia EA, Onuorah EC, Anya SU, Nnacheta TA (2012). Herbal Medicine: a survey of use in Nigerian presurgical patients booked for ambulatory anaesthesia. BMC Complementary and Alternative Medicine 12, 30. http://www.biomedcentral.com/1472-6882/12/130.
Amaeze OU, Aderemi-Williams RI, Ayo-Vaughan MA, Ogundemuren DA, Ogunmola DS, Anyika EN (2018). Herbal medicine use among Type 2
diabetes mellitus patients in Nigeria: understanding the magnitude and predictors of use. International Journal of Clinical Pharmacology 40(3): 580-588. doi: 10.1007/s11096-018-0648-2.
Amaeze OU, Olugbake OA, Lawal M (2020). Knowledge of Herbal Medicines and Herb-drug Interaction Among Medical and Pharmacy Students of the University of Lagos, Nigeria. Nigerian Journal of Pharmaceutical Research 16 (1): 61-70
Bent S (2008). Herbal medicine in the United States: review of efficacy, safety, and regulation: grand rounds at University of California, San
Francisco Medical Center. Journal of General Internal Medicine 23(6): 854-9. doi: 10.1007/s11606-008-0632-y.
Chang HY, Wallis M, Tiralongo E (2007). Use of complementary and alternative medicine among people living with diabetes: literature review. Journal of Advanced Nursing 58(4): 307-319. doi: 10.1111/j.1365-2648.2007.04291.x. [PubMed] [CrossRef] [Google Scholar]
Radwan H, Hasan H, Hamadeh R, Hashim M, AbdulWahid Z, Gerashi MH, Hilali MA, Naja F (2020). Complementary and alternative medicine
use among patients with type 2 diabetes living in the United Arab Emirates. BMC Complementary Medicine and Therapies 20: 216.
https://doi.org/10.1186/s12906-020-03011-5
Ezeome ER, Anarado AN (2007). Use of complementary and alternative medicine by cancer patients at the University of Nigeria Teaching
Hospital, Enugu, Nigeria. BMC Complementary and Alternative Medicine 7: 28. doi: 10.1186/1472- 6882-7-28.
Ogbera AO, Dada O, Adeyeye F, Jewo PI (2010). Complementary and alternative medicine use in diabetes mellitus. West African Journal of Medicine 29(3): 158-62. doi: 10.4314/wajm. v29i3.68213. PMID: 20665458.
Ilomuanya MO, Okubanjo OO, Azubuike C, Adeyemi O, Ajiboye D, Maduka C (2017). Evaluation of the frequency of use of herbal drugs with concomitant administration of highly active antiretroviral therapy and its effect on medication adherence in two healthcare facilities in South-Western Nigeria. Journal of AIDS and HIV Research 9 (1): 8-16. https://doi.org/10.5897/JAHR2016.0399
Gerber W, Steyn JD, Kotzé AF, Hamman JH (2018). Beneficial Pharmacokinetic Drug Interactions: A Tool to Improve the Bioavailability of Poorly Permeable Drugs. Pharmaceutics 10(3): 106. doi: 10.3390/pharmaceutics10030106.
Gurley BJ (2012). Pharmacokinetic herb-drug interactions (part 1): origins, mechanisms, and the impact of botanical dietary supplements. Planta medica 78(13): 1478-1489. https://doi.org/10.1055/s-0031-1298273.
Gupta RC, Chang D, Nammi S, Bensoussan A, Bilinski K, Roufogalis BD (2017). Interactions between antidiabetic drugs and herbs: an overview of mechanisms of action and clinical implications. Diabetology and Metabolic Syndrome 9: 59. doi: 10.1186/s13098-017-0254-9.
Izzo AA (2012). Interactions between herbs and conventional drugs: overview of the clinical data. Medical Principles and Practice 21(5): 404-28. doi: 10.1159/000334488. Epub 2012 Jan 11. PMID: 22236736.
Shi S, Klotz U (2012). Drug interactions with herbal medicines. Clinical Pharmacokinetics 51(2): 77-104. doi: 10.2165/11597910-000000000-00000. PMID: 22257149.
Bailey CJ (2017). Metformin: historical overview. Diabetologia 60: 1566-1576. https://doi.org/10.1007/s00125-017-4318-z
Rena G, Hardie DG, Pearson ER (2017). The mechanisms of action of metformin. Diabetologia 60: 1577-1585 https://doi.org/10.1007/s00125- 85 West African Journal of Pharmacy (2023) 34 (2) 017-4342-z
Graham GG, Punt J, Arora M, Day RO, Doogue MP, Duong JK, Furlong TJ, Greenfield JR, Greenup LC, Kirkpatrick CM, Ray JE, Timmins P, Williams KM (2011). Clinical Pharmacokinetics of Metformin. Clinical Pharmacokinetics 50(2): 81-98.
Kawoosa F, Shah ZA, Masoodi SR, Amin A, Rasool R, Fazili KM, Dar AH, Lone A, ul Bashir S (2022). Role of human organic cation transporter-1 (OCT- 1/SLC22A1) in modulating the response to metformin in patients with type 2 diabetes. BMC Endocrine Disorders 22: 140.
https://doi.org/10.1186/s12902-022-01033-3
Shu Y, Sheardown SA, Brown C, Owen RP, Zhang S, Castro RA, Ianculescu AG, Yue L, Lo JC, Burchard EG, Brett CM, Giacomini KM (2007). Effect of genetic variation in the organic cation transporter 1 (OCT1) on metformin action. The Journal of Clinical investigation 117(5): 1422-31. doi: 10.1172/JCI30558. PMID: 17476361; PMCID: PMC1857259.
Zolk O, Solbach TF, König J, Fromm MF (2009). Structural determinants of inhibitor interaction with the human organic cation transporter OCT2 (SLC22A2). Naunyn-Schmiedeberg's Archives of Pharmacology 379(4): 337-48. doi: 10.1007/s00210-008-0369-5. Epub 2008 Nov 11.
PMID: 19002438.
Kale OE, Akinpelu OB, Bakare AA, Yusuf FO, Gomba R, Araka D C, Ogundare T O, Okolie A C, Adebawo O, Odutola O (2018). Five traditional Nigerian Polyherbal remedies protect against high fructose fed, Streptozotocin-induced type 2 diabetes in male Wistar rats. BMC complementary and alternative medicine 18(1): 160. https://doi.org/10.1186/s12906-018-2225-6
Obasi DC, Ogugua VN (2021a). Effect of Ruzu Herbal Bitters on the Liver Function and Lipid Profile Parameters of Alloxan-Induced Diabetic Rats. Journal of Clinical and Experimental Hepatology DOI:10.1016/j.jceh.2021.09.012
Obasi DC, Ogugua VN (2021b). GC-MS analysis, pH and antioxidant effect of Ruzu herbal bitters on alloxan-induced diabetic rats. Biochemistry and Biophysics Reports 27: 101057. doi: 10.1016/j.bbrep.2021.101057.
Briggs ON, Elechi-amadi KN, Aleruchi-Didia TN, Anyalebechi E O, Agwor S (2022). Effects of the Anti- diabetic Polyherbal (Ruzu Bitters) on Glucose, Hepatic and Renal Parameters in Alloxan-induced Diabetic Rats. Journal of Advances in Medical and Pharmaceutical Sciences 24(4), 44-51. https://doi.org/10.9734/jamps/2022/v24i430296
Ogunlana OO, Ogunlana OE, Ugochukwu SK, Adeyemi AO (2018). Assessment of the Ameliorative Effect of Ruzu Herbal Bitters on the
Biochemical and Antioxidant Abnormalities Induced by High Fat Diet in Wistar Rats. International Journal of Pharmacology 14: 329-341. DOI: 10.3923/ijp.2018.329.341. https://scialert.net/abstract/?doi=ijp.2018.329.341
Ogunlana OO, Ogunlana OE, Adekunbi TS, Adetuyi BO, Adegboye BE, Iheagwam FN (2020). "Anti- inflammatory Mechanism of Ruzu Bitters on Diet- Induced Nonalcoholic Fatty Liver Disease in Male Wistar Rats", Evidence Based Complementary & Alternative Medicine
https://doi.org/10.1155/2020/5246725
Odangowei IO, Frank-Oputu A, Shonubi OO, Ruth OA (2022). Biochemical Study on the Effects of Ruzu Herbal Bitters Formulation on Wistar Albino Rats. Biomedical Journal of Scientific & Technical Research 41(1): DOI:10.26717/BJSTR.2022.41.006558
Valizadeh H, Nayyeri-Maleki P, Ghanbarzadeh S, Sheikhloo A, Servat H, Nemati M, Zekeri-Milani P (2014). Pharmacokinetics and bioequivalence of two brands of metformin 500 mg tablets in Iranian healthy volunteers. Journal of Pharmaceutical Investigation 44: 61-68. 10.1007/s40005-013- 0102-3 https://api.semanticscholar.org/CorpusID:256309835
Yuangang Zu, Chunying Li, Yujie Fu, Chunjian Zhao (2006). Simultaneous determination of catechin, 86 West African Journal of Pharmacy (2023) 34 (2) rutin, quercetin,kaempferol and isorhamnetin in the extract of sea buckthorn (Hippophae rhamnoidesL.) leaves by RP-HPLC with DAD. Journal of Pharmaceutical and Biomedical Analysis 41: 714- 719
Appiah-Opong R, Commanduer JN, Axson C, Vermeulen NP (2008). Interactions between cytochromes P450, glutathione S-transferases and
Ghanaian medicinal plants. Food and Chemical Toxicology 46: 3598-3603. doi: 10.1016/j.fct.2008.09.002. [PubMed] [CrossRef] [Google Scholar].
Yannan Li, Jing Ning, Yan Wang, Chao Wang, Chengpeng Sun, Xiaokui Huo, Zhenlong Yu, Lei Feng, Baojing Zhang, Xiangge Tian, Xiaochi Ma
(2018). Drug interaction study of flavonoids toward CYP3A4 and their quantitative structure activity relationship (QSAR) analysis for predicting
potential effects. Toxicology Letters 294: 27 - 36. https://doi.org/10.1016/j.toxlet.2018.05.008.
Stage TB, Brøsen K, Christensen MM. 2015. A Comprehensive Review of Drug-Drug Interactions with Metformin. Clinical Pharmacokinetics 54(8): 811-24. doi: 10.1007/s40262-015-0270-6. PMID: 25943187.
Sheleme T (2021). Clinical Pharmacokinetics of Metformin. Metformin - Pharmacology and Drug Interactions. IntechOpen DOI:
5772/intechopen.99343.
Pakkir Maideen, NM, Jumale A, Balasubramaniam R (2017). Drug Interactions of Metformin Involving Drug Transporter Proteins. Advanced
Pharmaceutical Bulletin 7(4):501-505. doi: 10.15171/apb.2017.062. Epub 2017 Dec 31. PMID: 29399540; PMCID: PMC5788205.