Archives of Pharmacal Research

The Pharmaceutical Society of Korea (대한약학회)
권호 표지

Pharmacokinetics of Acebutolol and Its Main Metabolite, Diacetolol After Oral Administration of Acebutolol in Rabbits with Carbon Tetrachloride-Induced Hepatic Failure

  • Published : 2002.08.01
Download PDF
⟨ Previous Next ⟩

Abstract

Pharmacokinetic characteristics of Acebutolol and its main metabolite, diacetolol, following a single 10 mg/kg oral dose, were investigated in rabbits with carbon tetrachloride-induced hepatic failure. Plasma concentrations of acebutolol and diacetolol were determined by a high performance liquid chromatography assay. The area under the plasma concentration-time curves (AUC) and maximum plasma concentration ($C_{max}$) of acebutolol were significantly increased in moderate and severe carbon tetrachloride-induced hepatic failure rabbits. The ratio of the diacetolol to total acebutolol in plasma (i.e., metabolite percentage rate) was significantly decreased in moderate and severe carbon tetrachloride-induced hepatic failure rabbits. Volume of distribution ($V_{d}$) and total body clearance ($CL_{t}$) of acebutolol were significantly decreased in moderate and severe carbon tetrachloride-induced hepatic failure rabbits. Slope of terminal phase ($\beta$) of acebutolol was significantly decreased in hepatic failure rabbits. These findings suggest that the $V_{d},{\;}CL_{t}$ and $\beta$ of acebutolol were significantly decreased as a result of inhibition of the hepatic metabolism in moderate to severe hepatic failure rabbits. Therefore, dose adjustment may be necessary for acebutolol in hypertensive patients with hepatic damage.

Keywords

References

  1. 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) https://doi.org/10.1016/0002-9343(78)90456-4
  2. 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. lnt. Med. Res., 7, 201-214 (1979)
  3. Basi, J. and Jordan, R., Pharmacological properties of ciacetolol, a major metabolite of acebutolol. Eur. J. Pharmacol., 80, 47-56 (1982) https://doi.org/10.1016/0014-2999(82)90176-5
  4. Borchard, U., Pharmacokinetics of beta-adrenoceptor blocking agents: clinical significance of hepatic and renal clearance. Clin. Physio.l Biochem., 8, 28-34(1990)
  5. Branch, R. A., Kornhauser, D. M., Shand, D. G., Wilkinson, G. R., and Wood , A. J., Biological determinants of propranolol disposition in normal subjects and patients with cirrhosis. J. Cin. Pharmacol. 4, 630-637 (1987)
  6. 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) https://doi.org/10.1016/S0378-4347(00)80496-X
  7. Castleden, C. M. and George, C. F., The effect of ageing on the hepatic clearance of propranolol. Br. J. Clin. Pharmacol., 3, 49-54 (1979)
  8. 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) https://doi.org/10.1007/BF00562806
  9. 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) https://doi.org/10.1111/j.2042-7158.1981.tb13811.x
  10. George, C. F. and Gruchy, B. S., Elimination of drugs by active intestinal transport. J. Pharm. Pharmacol., 31, 643-644 (1979) https://doi.org/10.1111/j.2042-7158.1979.tb13613.x
  11. 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) https://doi.org/10.1002/bdd.2510020202
  12. Homeida, M., Jackson, L. and Roberts, C. J., Decreased first-pass metabolism of labetalol in chronic liver disease. Br. Med. J., 14, 1048-1050 (1988)
  13. Lejeune, P., Desager, J. P., Meunier, H. and Harvengt, C., Kinetics of a single dose combination of acebutolol in patients with chronic liver disease. Intern. J. Clin. Pharm.Ther. Taxicol., 26, 513-516 (1988)
  14. 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) https://doi.org/10.1111/j.1365-2125.1978.tb00863.x
  15. 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. Ther., 24, 5-10 (1978) https://doi.org/10.1002/cpt19782415
  16. Regardh, C. G., Jordo, L., Ervik, M., Lundborg, P., Olsson, R. and Rann, O., Pharmacokinetics of metoprolol in patients with hepatic cirrhosis. Clin. Pharmacokinet., 6, 375-388 (1981) https://doi.org/10.2165/00003088-198106050-00004
  17. 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) https://doi.org/10.1111/j.1365-2125.1980.tb05837.x
  18. Yamaoka, K., Tanigawara, Y., Nakagawa, T. and Uno, T., A pharmacokinetics analysis program for microcomputer. J. Pharm. Dyn., 4, 879-883 (1971)
  19. Zaman, R., Jack, D. B., Wilkins, M. R. and Kendall, M. J., Lack of effect of liver disease on the pharmacokinetics of acebutolol and diacetolol: a single dose study. Biopharm. Drug Disp., 6, 131-137 (1985) https://doi.org/10.1002/bdd.2510060204