DOI QR코드

DOI QR Code

Effects of Hydrocortisone on the Pharmacokinetics of Loratadine after Oral and Intravenous Loratadine Administration to Rats

  • Published : 2009.04.30

Abstract

The present study investigated the effects of hydrocortisone on the pharmacokinetics of loratadine in rats after intravenous and oral administration. A single dose of loratadine was administered either orally (4 mg/kg) or intravenously (1 mg/kg) with or without oral hydrocortisone (0.3 or 1.0 mg/kg). Compared to the control group (without hydrocortisone), after oral administration of loratadine, the area under the plasma concentration-time curve (AUC) was significantly increased by 30.2-81.7% in the presence of hydrocortisone (p<0.05). The peak plasma concentration ($C_{max}$) was significantly increased by 68.4% in the presence of 1.0 mg/kg hydrocortisone after oral administration of loratadine (p<0.05). Hydrocortisone (1.0 mg/kg) significantly increased the terminal plasma half-life ($t_{1/2}$) of loratadine by 20.8% (p<0.05). Consequently, the relative bioavailability of loratadine was increased by 1.30- to 1.82-fold. In contrast, oral hydrocortisone had no effects on any pharmacokinetic parameters of loratadine given intravenously. This suggests that hydrocortisone may improve the oral bioavailability of loratadine by reducing first-pass metabolism of loratadine, most likely mediated by P-gp and/or CYP3A4 in the intestine and/or liver. In conclusion, hydrocortisone significantly enhanced the bioavailability of orally administered loratadine in rats, which may have been due to inhibition of both CYP 3A4-mediated metabolism and P-gp in the intestine and/or liver by the presence of hydrocortisone.

Keywords

References

  1. Amini, H. and Ahmadiani, A. (2004). Rapid determination of loratadine in small volume plasma samples by high-performance liquid chromatography with fluorescence detection. J. Chromatogr. B. Analyt. Technol. Biomed. Life Sci. 809, 227-230 https://doi.org/10.1016/j.jchromb.2004.06.022
  2. Benet, L. Z., Cummins, C. L. and Wu, C. Y. (2003). Transporter-enzyme interactions: implications for predicting drugdrug interactions from in vitro data. Curr. Drug Metab, 4, 393-398 https://doi.org/10.2174/1389200033489389
  3. Carr, R. A., Edmonds, A., Shi, H., Locke, C. S., Gustavson, L. E., Craft, J. C., Harris, S. I. and Palmer, R. (1998). Steady-state pharmacokinetics and electrocardiographic pharmacodynamics of clarithromycin and loratadine after individual or concomitant administration. Antimicrob. Agents Chemother. 42, 1176-1180
  4. Clissold, S. P., Sorkin, E. M., Goa, K. L. (1989). Loratadine, a preliminary review of its pharmacodynamic properties and therapeutic efficacy. Drugs 37, 42-57 https://doi.org/10.2165/00003495-198937010-00003
  5. Cummins, C. L., Jacobsen, W. and Benet, L. Z. (2002). Unmasking the dynamic interplay between intestinal P-glycoprotein and CYP3A4. J. Pharmacol. Exp. Ther. 300, 1036-1045 https://doi.org/10.1124/jpet.300.3.1036
  6. El-Sankary, W., Plant, N. J., Gibson, G. G. and Moore, D. J. (2000). Regulation of the CYP3A4 gene by hydrocortisone and xenobiotics: role of the glucocorticoid and pregnane X receptors. Drug Metab. Dispos. 28, 493-496
  7. Gibson, G. G., El-Sankary, W. and Plant, N. J. (2002). Receptordependent regulation of the CYP3A4 gene. Toxicology 181, 199-202 https://doi.org/10.1016/S0300-483X(02)00281-0
  8. Henz, B. M. (2001). The pharmacologic profile of desloratadine: a review. Allergy 56(Suppl), 65, 7-13 https://doi.org/10.1034/j.1398-9995.2001.00101.x
  9. Hilbert, J., Radwanski, E., Weglein, R., Luc, V., Perentesis, G., Symchowicz, S. and Zampaglione, N. (1987). Pharmacokinetics and dose proportionality of loratadine. J. Clin. Pharmacol. 27, 694-698 https://doi.org/10.1002/j.1552-4604.1987.tb03090.x
  10. Ito, K., Kusuhara, H. and Sugiyama, Y. (1999). Effects of intestinal CYP3A4 and P-glycoprotein on oral drug absorption; theoretical approach. Pharm. Res. 16, 225-231 https://doi.org/10.1023/A:1018872207437
  11. Kaminsky, L. S. and Fasco, M. J. (1991). Small intestinal cytochromes P450. Crit. Rev. Toxocol. 21, 407-422 https://doi.org/10.3109/10408449209089881
  12. Kosoglou, T., Salfi, M., Lim, J. M., Batra, V. K., Cayen, M. N. and Affrime, M. B. (2000). Evaluation of the pharmacokinetics and electrocardiographic pharmacodynamics of loratadine with concomitant administration of ketoconazole or cimetidine. Br. J. Clin. Pharmacol. 50, 581-589 https://doi.org/10.1046/j.1365-2125.2000.00290.x
  13. Kreutner, W., Hey, J. A., Anthes, J. and Barnett, A. (2000). Preclinical pharmacology of desloratadine, a selective and nonsedating histamine H1 receptor antagonist. 1st communication: receptor selectivity, antihistaminic activity, and antiallergenic effects. Arzneimittelforschung 50, 345-352
  14. Nakayama, A., Eguchi, O., Hatakeyama, M., Saitoh, H. and Takada, M. (1999). Different absorption behaviors among steroid hormones due to possible interaction with Pglycoprotein in the rat small intestine. Biol. Pharm. Bull. 22, 535-538 https://doi.org/10.1248/bpb.22.535
  15. Philpot, E. E. (2000). Safety of second generation antihistamines. Allerg. Asthma Proc. 21, 15-19 https://doi.org/10.2500/108854100778249033
  16. Pichard, L., Gillet, G., Fabre, I., Dalet-Beluche, I., Bonfils, C., Thenot, J. P. and Maurel, P. (1990). Identification of the rabbit and human cytochromes P-450 3A as the major enzymes involved in the N-demethylation of diltiazem. Drug Metab. Dispos. 18, 711-719
  17. Prenner, B. M., Capano, D. and Harris, A. G. (2000). Efficacy and tolerability of loratadine versus fexofenadine in the treatment of seasonal allergic rhinitis: a double-blind comparison with crossover treatment of nonresponders. Clin. Ther. 22, 760-769 https://doi.org/10.1016/S0149-2918(00)90009-2
  18. Ramaekers, J. G., Uiterwijk, M. M. and O'Hanlon, J. F. (1992). Effects of loratadine and cetirizine on actual driving and psychometric test performance and EEG during d-riving. Eur. J. Clin. Pharmacol. 42, 363-369 https://doi.org/10.1007/BF00280119
  19. Tarnasky, P. R. and Van Arsdel, P. P. (1990). Antihistamine therapy in allergic rhinitis. J. Fam. Prac. 30, 71-80
  20. Wacher, V. J., Silverman, J. A., Zhang, Y. and Benet, L. Z. (1998). Role of P-glycoprotein and cytochrome P450 3A in limiting oral absorption of peptides and peptidomimetics. J. Pharm. Sci. 87, 1322-1330 https://doi.org/10.1021/js980082d
  21. Wang, E. J., Casciano, C. N., Clement, R. P. and Johnson, W. W. (2001). Evaluation of the interaction of loratadine and desloratadine with P-glycoprotein. Drug. Metab. Dispo. 29, 1080-1083
  22. Wolozin, B., Kellman, W., Ruosseau, P., Celesia, G. G. and Siegel, G. (2000). Decreased prevalence of Alzheimer disease associated with 3-hydroxy-3-methyglutaryl coenzyme A reductase inhibitors. Arch. Neurol. 10, 1439-1443 https://doi.org/10.1001/archneur.57.10.1439
  23. Yates, C. R., Chang, C., Kearbey, J. D., Yasuda, K., Schuetz, E. G., Miller, D. D., Dalton, J. T. and Swaan, P. W. (2003). Structural determinants of P-glycoprotein-mediated transport of glucocorticoids. Pharm. Res. 20, 1794-1803 https://doi.org/10.1023/B:PHAM.0000003377.39548.f6
  24. Yin, O. Q., Shi, X. and Chow, M. S. (2003). Reliable and specific high-performance liquid chromatographic method for simultaneous determination of loratadine and its metabolite in human plasma. J. Chromatogr. B. Analyt. Technol. Biomed. Life Sci. 796, 165-172 https://doi.org/10.1016/j.jchromb.2003.08.023
  25. Yumibe, N., Huie, K., Chen, K. J., Snow, M., Clement, R. P. and Cayen, M. N. (1996). Identification of human liver cytochrome P450 enzymes that metabolize the nonsedating antihistamine loratadine. Formation of descarboethoxyloratadine by CYP3A4 and CYP2D6. Biochem. Pharmacol. 51, 165-172 https://doi.org/10.1016/0006-2952(95)02169-8
  26. Zhang, Y., Guo, X., Lin, E. T. and Benet, L. Z. (1998). Overlapping substrate specificities of cytochrome P450 3A and P-glycoprotein for a novel cysteine protease inhibitor. Drug Metab. Dispos. 26, 360-366

Cited by

  1. Negligible Effect of Ginkgo Biloba Extract on the Pharmacokinetics of Cilostazol vol.17, pp.3, 2009, https://doi.org/10.4062/biomolther.2009.17.3.311
  2. Monitoring of 35 illegally added steroid compounds in foods and dietary supplements vol.31, pp.9, 2014, https://doi.org/10.1080/19440049.2014.946100
  3. Screening for Corticosteroid Adulterants in Korean Herbal Medicines vol.61, pp.1, 2016, https://doi.org/10.1111/1556-4029.12906