Department of Pharmacology, College of Pharmacy, Mother Theresa Post Graduate and Research Institute of Health sciences, Puducherry, India.
Department of Pharmacology, College of Pharmacy, Mother Theresa Post Graduate and Research Institute of Health sciences, Puducherry, India.
* Corresponding author

Article Main Content

P-glycoprotein, an efflux transporter prevents intracellular accumulation of xenobiotics. Cyclosporine A and acitretin are used to treat psoriasis. The present research work aims to investigate the possible role of P-glycoprotein in Cyclosporine- Acitretin drug interaction due to evidence of both drugs having affinity for P-glycoprotein.The study has three different objective namely to assess apparent permeability coefficient of cyclosporine in presence of acitretin by non-everted sac technique, to study the intestinal permeation and absorption kinetics of cyclosporine in presence of acitretin by single pass intestinal perfusion (SPIP) technique and to study the influence of acitretin on oral bioavailability of cyclosporine in Wistar rats.The result of ex vivo, in situ and in vivo study showed that cyclosporine level increased in a time dependent manner. As the dose of acitretin increases the cyclosporine concentration in all three methods tend to increase and was statistically significant. The improvement in absorption of cyclosporine may be due to the inhibition of P-glycoprotein transporter in the intestine by acitretin. Thus acitretin may enhance the oral pharmacokinetics of cyclosporine. Hence this combination may require close monitoring for better therapeutic outcome. Our study confirmed the inhibitory role of acitretin on P-glycoprotein leading to increase concentration of cyclosporine.

References

  1. FJ. Sharom, “The P-Glycoprotein Multidrug Transporter,” Essays Biochem, Vol. 50, No. 1, pp 161-78, Sep. 2011.
    DOI  |   Google Scholar
  2. L. Saaby, B. A. Brodin, “Critical View on In vitro Analysis of P-glycoprotein (P-gp) Transport Kinetics,” Journal of Pharmaceutical Science, vol. 106, no. 9, pp 2257-64, Sep 2017.
    DOI  |   Google Scholar
  3. RL. Linardi, CC. Natalini, “Multi-drug resistance (MDR1) gene and P-glycoprotein Influence on pharmacokinetic and pharmacodymanic of therapeutic drugs,” Ciencia Rural, vol. 36, no. 1, pp. 336-41, Jan 2006.
    DOI  |   Google Scholar
  4. J T.Shikawa, H.Hirano, Y.Onishi, A.Sakurai, S.Tarui, “Functional Evaluation of ABCB 1 (P-Glycoprotein) Polymorphisms: High-Speed Screening and Structure-Activity Relationship Analyses,” Drug Metab Pharmacokinet, Vol.19, No.1, pp. 1-14, Feb 2004.
    DOI  |   Google Scholar
  5. ALA. Kuijpers, RJ. Van Dooren-Greebe, PCM. Van de Kerkhof, “Failure of Combination Therapy with Acitretin and Cyclosporin A in 3 Patients with Erythrodermic Psoriasis,” Dermatolog, Vol. 194, No. 1, pp. 88-90, 1997.
    DOI  |   Google Scholar
  6. C. Chang, PM. Bahadduri, JE. Polli, PW. Swaan, S.Ekins, “Rapid Indentification of P-Glycoprotein Substrates and Inhibitors,” Drug Metab Dispos, Vol. 34, 12, pp. 1976-84, Dec 2006.
    DOI  |   Google Scholar
  7. BL. Athukuri, P. Neerati, “Enhanced Oral Bioavailability of Domperidone with Piperine in Male Wistar Rats: Involvement of CYP3A1 and P-gp Inhibition,” J Pharm Pharm Sci, vol. 20, pp. 28-37, Jan 2017.
    DOI  |   Google Scholar
  8. Wahajuddin, KSR. Raju, SP. Singh, I. Taneja, “Investigation of the functional role of p-glycoprotein in limiting the oral bioavailability of lumefantrine,” Antimicrob Agents chemother, vol. 8, no. 1, pp. 489-94,
    DOI  |   Google Scholar
  9. Jan 2014.
     Google Scholar
  10. R. Jain, S. Duvvuri,V. Kansara, NK. Mandava, AK. Mitra,“Intestinal absorption of novel-dipeptide prodrugs of saquinavir in rats,”Int J Pharm, vol. 336, no. 2, pp. 233-40, May 2007.
    DOI  |   Google Scholar
  11. S. Yigitaslan, K. Erol, C. Cengelli, “The effect of p-glycoprotein inhibition and activation on the absorption and serum levels of cyclosporine and tacrolimus in rats,” Adv Clin Exp Med, vol. 25, no. 2, pp. 237-42, Mar-Apr 2016.
    DOI  |   Google Scholar
  12. D.Tsambaos, K.Bolsen, S.Georgiou, A.Kalofoutis, G.Goerz, “Effect of Oral Administration of Acitretin on Rat Liver Microsomal phospholipids, P-450 Content and Monooxygenase,” Skin Pharmacol, vol. 7, pp. 320-3, Mar 1994.
    DOI  |   Google Scholar
  13. A. Parsa, R. Saadati, Z. Abbasian, S. Azad Aramaki, S. Dadashzadeh, “Enhanced Permeability of Etoposide across Everted Sacs of Rat Small Intestine by Vitamin E-TPGS,” Iran J Pharm Res, vol. 12, pp. 37-46, Mar 2013.
     Google Scholar