Effects of Resveratrol Co-Administration on Celecoxib Disposition and
                    Pharmacokinetics in Healthy Volunteers

Nagwa I. Helal; Noha M. El-Khodary; Gamal A. Omran; Soha M. El-Masry

doi:10.1055/a-2160-2186

Drug Research, Table of Contents

Drug Res (Stuttg) 2023; 73(09): 520-527
DOI: 10.1055/a-2160-2186

Original Article

Effects of Resveratrol Co-Administration on Celecoxib Disposition and Pharmacokinetics in Healthy Volunteers

Nagwa I. Helal

¹Department of Clinical Pharmacy & Pharmacy Practice, Faculty of Pharmacy Damanhour University, Damanhour City, Egypt

,

Noha M. El-Khodary

²Department of Clinical Pharmacy, Faculty of Pharmacy Kafrelsheikh University, Kafrelsheikh City, Egypt

,

Gamal A. Omran

³Department of Biochemistry, Faculty of Pharmacy Damanhour University, Damanhour City, Egypt

,

Soha M. El-Masry

⁴Department of Pharmaceutics, Faculty of Pharmacy Damanhour University, Damanhour City, Egypt

› Author Affiliations

Abstract

The objective of the current study was to investigate the effects of resveratrol (RSV), a natural herbal remedy used as an adjacent anti-inflammatory supplement on, the pharmacokinetics of celecoxib in healthy male volunteers. Twelve healthy human participants were involved in two-period open-labeled trial. Celecoxib (200 mg) was given as a single oral dose under fasting conditions as a control phase. Afterward, RSV (500 mg) commenced as a single oral dose for ten days as a treatment phase. Blood samples were collected during the control and treatment phases and analyzed using the validated High-performance liquid chromatography (HPLC) method. RSV pre-exposure significantly increased the area under the curve (AUC_0–24), peak plasma concentration (C_max), absorption rate constant (ka), and prolongated half-life (t_1/2), along with a decrease in elimination rate constant (ke). Meanwhile, the volume of distribution (Vd/F) and apparent total body clearance (CL/F) were significantly decreased for celecoxib. There was no significant change in the time it takes for celecoxib to reach the maximum concentration (t_max) was observed. The obtained results suggested the presence of a beneficial pharmacokinetic interaction between RSV and celecoxib. Consequently, combining resveratrol as an herbal remedy and celecoxib as an anti-inflammatory drug may synergistically reduce inflammation and osteoarthritis with minimal side effects.

Key words

Resveratrol - celecoxib - P-glycoprotein - CYP2C9 - CYP3A4 - pharmacokinetic interactions

Full Text

References

References
1 Chen YF, Jobanputra P, Barton P. et al Cyclooxygenase-2 selective non-steroidal anti-inflammatory drugs (etodolac, meloxicam, celecoxib, rofecoxib, etoricoxib, valdecoxib and lumiracoxib) for osteoarthritis and rheumatoid arthritis: a systematic review and economic evaluation. Health Technol Assess 2008; 12: 1-278 iii
2 Fung HB, Kirschenbaum HL. Selective cyclooxygenase-2 inhibitors for the treatment of arthritis. Clin Ther 1999; 21: 1131-1157
3 Sostres C, Gargallo CJ, Arroyo MT. et al. Adverse effects of non-steroidal anti-inflammatory drugs (NSAIDs, aspirin and coxibs) on upper gastrointestinal tract. Best Pract Res Clin Gastroenterol 2010; 24: 121-132
4 García-Rayado G, Navarro M, Lanas A. NSAID induced gastrointestinal damage and designing GI-sparing NSAIDs. Expert Rev Clin Pharmacol 2018; 11: 1031-1043
5 Thomas D, Ali Z, Zachariah S. et al. Coxibs Refocus Attention on the Cardiovascular Risks of Non-Aspirin NSAIDs. Am J Cardiovasc Drugs 2017; 17: 497-498
6 Barcella CA, Lamberts M, McGettigan P. et al. Differences in cardiovascular safety with non-steroidal anti-inflammatory drug therapy – A nationwide study in patients with osteoarthritis. Basic Clin Pharmacol Toxicol 2019; 124: 629-641
7 Sandberg M, Yasar Ü, Strömberg P. et al. Oxidation of celecoxib by polymorphic cytochrome P450 2C9 and alcohol dehydrogenase. Br J Clin Pharmacol 2002; 54: 423-429
8 Yan YX, Li WZ, Huang YQ. et al. The COX-2 inhibitor Celecoxib enhances the sensitivity of KB/VCR oral cancer cell lines to Vincristine by down-regulating P-glycoprotein expression and function. Prostaglandins Other Lipid Mediat 2012; 97: 29-35
9 Soleas GJ, Diamandis EP, Goldberg DM. Resveratrol: a molecule whose time has come? And gone?. Clin Biochem 1997; 30: 91-113
10 Kaur A, Tiwari R, Tiwari G. et al. Resveratrol: A Vital Therapeutic Agent with Multiple Health Benefits. Drug Res (Stuttg) 2022; 72: 5-17
11 Kung H-C, Lin K-J, Kung C-T. et al. Oxidative stress, mitochondrial dysfunction, and neuroprotection of polyphenols with respect to resveratrol in Parkinson’s disease. Biomedicines. 2021; 9: 918
12 Ansari MY, Ahmad N, Haqqi TM. Oxidative stress and inflammation in osteoarthritis pathogenesis: Role of polyphenols. Biomed Pharmacother 2020; 129: 110452
13 Jiang M, Li X, Yu X. et al. Oral administration of resveratrol alleviates osteoarthritis pathology in C57BL/6J mice model induced by a high-fat diet. Mediators Inflamm. 2017 7659023. doi: 10.1155/2017/7659023
14 Ma C, Wang Y, Dong L. et al. Anti-inflammatory effect of resveratrol through the suppression of NF-κB and JAK/STAT signaling pathways. Acta Biochim Biophys Sin (Shanghai) 2015; 47: 207-213
15 Marouf BH, Hussain SA, Ali ZS. et al. Clinical efficacy of resveratrol as an adjuvant with meloxican in the treatment of knee osteoarthritis patients: A double-blind, randomised, placebo-controlled trial. Braz J Pharm Sci 2018; 54: e17773
16 Robinson K, Mock C, Liang D. Pre-formulation studies of resveratrol. Drug Dev Ind Pharm 2015; 41: 1464-1469
17 Chan WK, Delucchi AB. Resveratrol, a red wine constituent, is a mechanism-based inactivator of cytochrome P450 3A4. Life Sci 2000; 67: 3103-3112
18 Bedada SK, Yellu NR, Neerati P. Effect of resveratrol on the pharmacokinetics of fexofenadine in rats: Involvement of P-glycoprotein inhibition. Pharmacol Rep 2016; 68: 338-343
19 Cassileth BR, Heitzer M, Wesa K. The public health impact of herbs and nutritional supplements. Pharm Biol 2009; 47: 761-767
20 Rombolà L, Scuteri D, Marilisa S. et al. Pharmacokinetic interactions between herbal medicines and drugs: their mechanisms and clinical relevance. Life (Basel) 2020; 10: 106
21 Abdelkawy KS, Abdelaziz RM, Abdelmageed AM. et al. Effects of green tea extract on atorvastatin pharmacokinetics in healthy volunteers. Eur J Drug Metab Pharmacokinet 2020; 45: 351-360
22 Athukuri B, Neerati P. Enhanced oral bioavailability of diltiazem by resveratrol in healthy human subjects: an open-label, two-period, sequential study. J Nat Sci Biol Med 2020; 11
23 Jia Y, Liu Z, Wang C. et al. P-gp, MRP2 and OAT1/OAT3 mediate the drug-drug interaction between resveratrol and methotrexate. Toxicol Appl Pharmacol 2016; 306: 27-35
24 Helmy SA, El-Bedaiwy HM, El-Masry SM. Effect of pineapple juice on the pharmacokinetics of celecoxib and montelukast in humans. Ther Deliv 2020; 11: 301-11.
25 Chen ML, Shah V, Patnaik R. et al. Bioavailability and bioequivalence: an FDA regulatory overview. Pharm Res 2001; 18: 1645-1650
26 US Dept of Health and Human Services, Food and Drug Administration, Center for Drug Evaluation and Research and Center for Veterinary Medicine. Guidance for Industry. Bioanalytical Method Validation, May 2018. Available from: https://www.fda.gov/files/drugs/published/Bioanalytical-Method-Validation-Guidance-for-Industry.pdf (Last assessed July, 2023)
27 International Conference on Harmonisation of Technical Requirements for Registration of Pharmaceuticals for Human use. ICH harmonised tripartite guideline: guideline for good clinical practice (2018). available from https://cc.bingj.com/cache.aspx?q = 19.+International+Conference+on+Harmonisation+of+Technical+Requirements+for+Registration+of+Pharmaceuticals+for+Human+use.+ICH++harmonised+tripartite+guideline%3a+guideline+for+good+clinical+practice.+(2018).+&d=5019988066780405&mkt=en-XA&setlang=en-US&w=u5fVPor7lJbq0674YgLSlh05wmduANTL
28 Hedaya MA. Basic Pharmacokinetics (2nd ed.). 2012. Routledge; accessed February 10, 2012.
29 Foster DavidM., Vicini Paolo. Chapter 8 - Noncompartmental and compartmental approaches to pharmacokinetic data analysis, Editor(s): Shiew-Mei Huang, Juan J.L. Lertora, Paolo Vicini, Arthur J. Atkinson, Atkinson’s Principles of Clinical Pharmacology (Fourth Edition). Elsevier; 2022: 113-135 https://www.sciencedirect.com/science/article/pii/B9780128198698000355
30 SAS Institute Inc. SAS/STAT User’s Guide, Version 6 4th Edition, Vol. 2, SAS Institute, NC, USA accessed 1990.
31 Diletti E, Hauschke D, Steinijans VW. Sample size determination for bioequivalence assessment by means of confidence intervals. Int J Clin Pharmacol Ther Toxicol 1992; 30: S51-S58
32 Chow SC. Bioavailability and bioequivalence in drug development. Wiley Interdiscip Rev Comput Stat 2014; 6: 304-312
33 Sakpal TV. Sample size estimation in clinical trial. Perspect Clin Res 2010; 1: 67
34 Shein-Shung C, Jun S, Hansheng W. " Sample Size Calculations in Clinical Research (3rd ed.). ". New York: 2003. Available at
35 ICH Topic E 9, Statistical Principal for Clinical Trials Step 4, Consensus guideline, 05Feb1998 Note for Guidance On Statistical Principles For Clinical Trial. Available at http://www.ich.org
36 Dinić J, Podolski-Renić A, Jeremić M. et al. Potential of natural-based anticancer compounds for P-glycoprotein inhibition. Curr Pharm Des 2018; 24: 4334-54.
37 Rahman MM, Islam MR, Shohag S. et al. The multifunctional role of herbal products in the management of diabetes and obesity: a comprehensive review. Molecules. 2022; 27: 1713
38 Lim JW, Chee SX, Wong WJ. et al. Traditional Chinese medicine: herb-drug interactions with aspirin. Singapore Med J 2018; 59: 230
39 Khojah HM, Ahmed S, Abdel-Rahman MS. et al. Resveratrol as an effective adjuvant therapy in the management of rheumatoid arthritis: a clinical study. Clin Rheumatol 2018; 37: 2035-42.
40 Manna SK, Mukhopadhyay A, Aggarwal BB. Resveratrol suppresses TNF-induced activation of nuclear transcription factors NF-κB, activator protein-1, and apoptosis: potential role of reactive oxygen intermediates and lipid peroxidation. J Immunol 2000; 164: 6509-6519
41 Li X, Li F, Wang F. et al. Resveratrol inhibits the proliferation of A549 cells by inhibiting the expression of COX-2. Onco Targets Ther 2018; 11: 2981
42 Pirola L, Fröjdö S. Resveratrol: one molecule, many targets. IUBMB life 2008; 60: 323-332
43 Adhami VM, Afaq F, Ahmad N. Suppression of ultraviolet B exposure-mediated activation of NF-κB in normal human keratinocytes by resveratrol. Neoplasia. 2003; 5: 74-82
44 Song Y, Li C, Liu G. et al. Drug-Metabolizing Cytochrome P450 Enzymes Have Multifarious Influences on Treatment Outcomes. Clin Pharmacokinet 2021; 60: 585-601
45 Younas M, Hano C, Giglioli-Guivarc’h N. et al. Mechanistic evaluation of phytochemicals in breast cancer remedy: current understanding and future perspectives. RSC Adv 2018; 8: 29714-44
46 Pervaiz S, Holme AL. Resveratrol: its biologic targets and functional activity. Antioxid Redox Signal 2009; 11: 2851-2897
47 Davies NM, McLachlan AJ, Day RO. et al. Clinical pharmacokinetics and pharmacodynamics of celecoxib: a selective cyclo-oxygenase-2 inhibitor. Clin Pharmacokinet 2000; 38: 225-242
48 Zubiaur P, Koller D, Saiz-Rodríguez M. et al. Important pharmacogenetic information for drugs prescribed during the SARS-CoV-2 infection (COVID-19). Clin Transl Sci 2020; 13: 1023-1033
49 Detampel P, Beck M, Krähenbühl S. et al. Drug interaction potential of resveratrol. Drug Metab Rev 2012; 44: 253-265