Effect of Curcumin at Various Doses on the Pharmacokinetic Profile of Tacrolimus in Healthy Rabbits

Authors

  • Issam Mohammed Abushammala Assoc. Professor, Department of Pharmaceutics and Industrial Pharmacy, Faculty of Pharmacy, al-Azhar University, Gaza/Palestine
  • Belal Mohammed Mqat
  • Abdallah Mohammed Hamdan

DOI:

https://doi.org/10.31351/vol31iss1pp246-250

Keywords:

Tacrolimus, Curcumin, CYP 3A4, Herb-drug interaction, Pharmacokinetics

Abstract

The purpose of present study is to evaluate the effect of co-administration of curcumin (CUR) at various doses on the pharmacokinetic (PK) profile of tacrolimus (TAC), a CYP 3A4 substrate in healthy male rabbits. Healthy male rabbits (n=18) were employed in an in vivo, parallel-randomized study. Three groups of rabbits were selected and separated: The rabbits in the first group (control group) received 1 mg/kg TAC orally. Blood samples (1.5-2 mL) were drawn from rabbits' ear marginal veins at the following time frames:  15.0, 30.0, 45.0, 60.0, 90.0, 120.0, 150.0, 180.0 and 300 minutes after TAC administration post dosing and analyzed by using a TAC chemiluminescent enzyme immunoassay (CLIA) detection kit. In the second and third groups (test groups), rabbits received TAC (1mg/kg) at identical conditions as in the control group with volumes equivalent to (30 and 90 mg/kg/day) of prepared CUR suspension in normal saline for seven continuous days. Blood samples from the control group were obtained on the eighth day. Non-compartmental analysis was used to derive different PK parameters of TAC for the three groups. When CUR was co-administered at both concentrations, insignificant statistically small changes between the control and testing groups were found. Our results revealed that the differences for the three groups in PK parameters as Cmax, tmax, ke, AUC0-6 and AUC0-? were statistically insignificant (P>0.05). In conclusion, it has been found that CUR at the experimented doses does not affect the PK of TAC. Further confirmation of our findings is requiered before these results can be applied in patient care.

 

References

Schutte-Nutgen K, Tholking G, and Suwelack B, et al. Tacrolimus- Pharmacokinetic Considerations for Clinicians. Current Drug Metabolism. 2018;19:342-350.

Van Gelder T. Drug interactions with tacrolimus. Drug Safty. 2002;25:707-712.

Zhai X, Chen C, and Xu X, et al. Marked change in blood tacrolimus concentration levels due to grapefruit in a renal transplant patient. Journal of Clinical Pharmacy and Therapeutics. 2019; 44:819-822.

Christians U, Jacobsen W, and Benet LZ, et al. Mechanisms of clinically relevant drug interactions associated with tacrolimus. Clinical Pharmacokinetics. 2002;41:813-851.

Manikandan P, Nagini S. Cytochrome P450 Structure, Function and Clinical Significance: A Review. Current Drug Targets. 2018;19:38-54.

Newman DJ, Cragg GM, Snader KM. Natural products as sources of new drugs over the period. Journal of Natural Products. 2003;66:1022e1037.

Pandit S, Kim H, and Kim J, et al. Separation of an effective fraction from turmeric against Streptococcus mutans biofilms by the comparison of curcuminoid content and anti-acidogenic activity. Food Chemistry. 2011;126:1565-1570.

Paramasivam M, Poi R, and Banerjee H, et al. High-performance thin layer chromatographic method for quantitative determination of curcuminoids in Curcuma longa germplasm. Food Chemistry. 2009;113:640-644.

Tarirai C, Viljoen AM, Hamman JH. Herb-drug pharmacokinetic interactions reviewed. Expert Opinion on Drug Metabolism and Toxicology. 2010;6:1515-1538.

Bahramsoltani R, Rahimi R, Farzaei MH. Pharmacokinetic interactions of curcuminoids with conventional drugs: A review. Journal of Ethnopharmacology. 2017;209:1-12.

Quintieri L, Palatini P, Nassi A, Ruzza P, et al. Flavonoids diosmetin and luteolin inhibit midazolam metabolism by human liver microsomes and recombinant CYP 3A4 and CYP3A5 enzymes. Biochemical Pharmacology. 2008; 75:1426-1437.

Fasinu PS, Bouic PJ, Rosenkranz B. An overview of the evidence and mechanisms of herb-drug interactions. Frontiers in Pharmacology. 2012;3:69.

Hsieh YW, Huang CY, and Yang SY, et al. Oral intake of curcumin markedly activated CYP 3A4: in vivo and ex-vivo studies. Scientific Reports. 2014;4:6587.

Parasuraman S, Raveendran R, Kesavan R. Blood sample collection in small laboratory animals, Journal of Pharmacology and Pharmacotherapeutics. 2010; 1:87–93.

Staatz CE, Tett SE. Clinical pharmacokinetics and pharmacodynamics of tacrolimus in solid organ transplantation. Clinical Pharmacokinetics. 2004;43:623-653.

Wanwimolruk S, Prachayasittikul V. Cytochrome P450 enzyme mediated herbal drug interactions (Part 1). EXCLI Journal. 2014;13:347-391.

Iwasaki K. Metabolism of tacrolimus (FK506) and recent topics in clinical pharmacokinetics. Drug Metabolism and Pharmacokinetics. 2007;22:328-335.

Hebert MF, Park JM, and Chen YL, et al. Effects of St John’s wort (Hypericum perforatum) on tacrolimus pharmacokinetics in healthy volunteers. Journal of Clinical Pharmacology. 2004;44: 89–94.

Dave AA, Samuel J. Suspected Interaction of Cranberry Juice Extracts and Tacrolimus Serum Levels: A Case Report. Cureus. 2016;8:610.

Beppu N, Mori T, and Kato J, et al. Drug-herbal interaction between tacrolimus and rooibos tea in a recipient of allogeneic hematopoietic stem cell transplantation. Journal of Hematopoietic Cell Transplantation. 2013;2:109-111.

Carbajal R, Yisfalem A, and Pradhan N, et al. Case report: boldo (Peumus boldus) and tacrolimus interaction in a renal transplant patient. Transplantion Proceedings. 2014;46:2400-2402.

Peynaud D, Charpiat B, and Vial T, et al. Tacrolimus severe overdosage after intake of masked grapefruit in orange marmalade. European Journal of Clinical Pharmacology. 2007;63:721-2.

Xiao-ling Q, Jia-li L, and Si-han W, et al. Co-administration of Wuzhi tablet (Schisandra sphenanthera extract) alters tacrolimus pharmacokinetics in a dose- and time-dependent manner in rats. Journal of Ethnopharmacology. 2020;263:113233.

Egashira K, Sasaki H, and Higuchi S, et al. Food-drug interaction of tacrolimus with pomelo, ginger, and turmeric juice in rats. Drug Metabolism and Pharmacokinetics. 2012;27:242-247.

Mauro VF, Mauro LS, and Kleshinski JF, et al. Impact of Ginkgo biloba on the pharmacokinetics of digoxin. American journal of therapeutics. 2003;10:247-251.

Xin HW, Wu XC, and Li Q, et al. The effects of berberine on the pharmacokinetics of cyclosporin A in healthy volunteers. Methods and Findings in Experimantal and Clinical Pharmacology. 2006;28:25-29.

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.

Liu AC, Zhao LX, Lou HX. Curcumin alters the pharmacokinetics of warfarin and clopidogrel in Wistar rats but has no effect on anticoagulation or antiplatelet aggregation. Planta Medica. 2013;79:971-977.

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Published

2022-06-23