Abstract
Because physiological changes that potentially alter pharmacokinetics occurs in diabetes mellitus patients, pharamacokinetics of drugs used in the treatment of hypertension was studied using acebutolol as a model anti-hypertensive drug. Thus, the pharmacokinetics of acebutolol was investigated after oral administration of acebutolol (15 mg/kg) to control rabbits and rabbits with acute or chronic diabetes mellitus induced by alloxan. Kidney and liver functions were documented for acute and chronic diabetes mellitus groups based on plasma chemistry data. After oral administration of acebutolol to acute and chronic groups, the plasma concentrations appeared higher; As a result, area under the plasma concentration-time curve from time zero to time infinityl0575 and 8668 μg h/mL for acute and chronic group, respectively. In comparison, the area was apparently smaller in the control group (i.e., 7132 μgh/mL). The half-life in acute groups was significantly prolonged 8.45 h compared with the half-life in the control group (i.e., 6.30 h). Alteration in acebutolol pharmacokinetics was more pronounced in the acute group as evidenced by the significantly higher values the area under the plasma concentration time curve, absorption rate constant and maximum plasma concentration compared with chronic or control group. Therefore, these observations indicate that acebutolol pharmacokinetics may be affected in patients with diabetes mellitus, especially in the early stage of the disease
Similar content being viewed by others
References
Alhenz-Gelas, F., Plouin, P. F., Ducrocq, M. B., Corvol, P. E., and Menard, J., Comparison of the antihypertensive and hormonal effects of a cardioselective beta-blocker acebutolol and diuretics in essential hypertension.Am. J. Med., 64, 1005–1012 (1978).
Baker, P. G. and Goulton, J. A., Multicentre study of a once daily dosage of acebutolol in the treatment of hypertension in general practice.J. Int. Med. Res., 7, 201–214 (1979).
Basil, J. and Jordan, R., Pharmacological properties of diacetolol, a major metabolite of acebutolol.Eur. J. Pharmacol., 80, 47–56 (1982).
Buskin, J. N., Upton, R. A., Jones, R., and Williams, R. L., High performance liquid chromatography assay of acebutolol and its metabolites in plasma and urine.J. Chromatogr., 230, 438–442 (1982).
Choi, Y. J., Lee, H. J., Kwon, J. W., Kim, W. B., Yang, J., and Lee, M. G., Pharmacokinetic change of M1, M2, M3, and M4 after intravenous administration of a new anthracycline, DA-125, to alloxan-induced diabetes mellitus.Res. Commun. Mol. Pathol. Pharmacol., 94, 181–192 (1996).
Choi, J. S. and Kim, Y.G., Pharmacokinetic changes of diltiazem anddesacetyldiltiazem after oral administration of diltiazem in rabbits with diabetes mellitus induced by alloxan.Biopharm. Drug Dispos., 23, 115–120 (2002)
Choi, J. S. and Choi, B. C., Pharmacokinetic changes of sulfamethoxazole in rabbits with diabetes mellitus induced by alloxan.Res. Commun. Mol. Pathol. Pharmacol., 108, 332–340 (2000).
Flouvat, B., Roux, A., and Chau, N. P., Pharmacokinetics and bioavailability of diacetolol, the main matabolite of acebutolol.Eur. J. Clin. Pharmacol., 19, 287–292 (1981).
Gwilt, P. R., Nahhas, P. R., and Tracewell, W. G., The effects of diabetes mellitus on pharmacokinetics and pharmacodynamics in humans.Clin. Pharmacokinet, 20, 477–490 (1991).
Gabriel, R., Kaye, C. M., and Sankey, M. G., Preliminary observations on the excretion of acebutolol and its acetyl matabolite in the urine and feces of man.J. Pharm. Pharmacol., 33, 386–387 (1981).
George, C. F. and Gruchy, B. S., Elimination of drugs by active intestinal transport.J. Pharm. Pharmacol., 31, 643–644 (1979).
Gulaid, A. A., James, I. M., and Kaye, C. M., The Pharmacokinetics of acebutolol in man, following the oral administration of acebutolol as a single dose and during and after repeated oral dosing.Biopharm. Drug Dispos., 2, 103–114 (1981).
Kim, S. H., Kim, W. B., and Lee, M. G., Pharmacokinetics of a new carbapenem, DA-1131, after intravenous administration to rats with alloxan-induced diabetes mellitus.Biopharm. Drug Dispos., 19, 303–308 (1998).
Lee, H. J., Paik, W. H., and Lee, M. G., Pharmacokinetic and tissue distribution changes of adriamycin and adriamycinol after intravenous administration of adriamycin to alloxan-induced diabetes mellitus rats.Res. Commun. Mol. Pathol. Pharmacol., 89, 165–178. (1995).
Martin, M. A., Phillips, C. A., and Smith, A. J., Acebutolol in hypertension a double blind trial against placebo.Br. J. Clin. Pharmcol., 6, 351–356 (1978).
Mclean, A. J., Mcnamara, R. J., Souich, P. D., Gibaldi, M., and Lalka, D., Food, splanchnic blood flow and bioavailability of drugs subject to first pass metabolism.Clin. Pharmacol. Then., 24, 5–10 (1978).
O’Connor, P. and Feely, J., Clinical pharmacokinetics and endocrine disorders. Therapeutic implications.Clin. Pharmacokinet., 13, 345–364 (1987).
Park, J. H., Lee, W. I., and Lee, M. G., Pharmacokinetic and pharmacodynamic changes of furosemide after intravenous and oral administration to rats with alloxan-induced diabetes mellitus.Biopharm. Drug Dispos., 19, 357–364 (1998).
Park, K. J., Yoon, W. H., and Lee, M.G., Pharmacokinetics and pharmacodynamics of azosemide after intravenous and oral administration to rats with alloxan-induced diabetes mellitus.J. Pharm. Pharmacol., 48, 1093–1097 (1996).
Pickup, J. C. and Williams, G., Textbook of Diabetes, Blackwell Scientific Publications, Oxford, England, 1, 151–155 (1991).
Roux, A., Flouvat, B., Chau, N. P., Letac, B. and Lucsko, B., Pharmacokinetics of acebutolol after intravenous bolus administration.Br. J. Clin. Pharmacol., 9, 215–217 (1980).
Yamaoka, K., Tanigawara, Y., Nakagawa, T., and Uno, T., A pharmacokinetics analysis program for microcomputer.J. Pharm. Dyn., 4, 879–883 (1971).
Author information
Authors and Affiliations
Corresponding author
Rights and permissions
About this article
Cite this article
Choi, D.H., Bae, H.Y. & Choi, J.S. Pharmacokinetic changes of acebutolol after orall administration in rabbits with diabetes mellitus induced by Alloxan. Arch Pharm Res 26, 499–503 (2003). https://doi.org/10.1007/BF02976870
Received:
Issue Date:
DOI: https://doi.org/10.1007/BF02976870