Abstract
The effect of chronic liver disease on the rate of elimination and extent of "first-pass" metabolism of labetalol was studied. Pharmacokinetic measurements were made after both oral and intravenous administration to seven healthy subjects and to 10 patients with chronic liver disease. Plasma half life was similar in the two groups. Plasma concentrations were considerably higher in the patients than in the healthy subjects after oral administration but similar after intravenous injection. Thus the bioavailability of labetalol was increased in liver disease due to reduced first-pass metabolism. Bioavailability in the group of patients correlated negatively with serum albumin concentration. There were falls in supine heart rate and blood pressure which tended to be greater after oral administration in the patients with liver disease, suggesting an exaggerated response related to the increased bioavailability. Oral dosage requirements of labetalol and possibly other drugs susceptible to first-pass metabolism are reduced in the presence of liver disease.
Full text
PDF


Selected References
These references are in PubMed. This may not be the complete list of references from this article.
- Ablad B., Borg K. O., Johnsson G., Regårdh C. G., Sölvell L. Combined pharmacokinetic and pharmacodynamic studies on alprenolol and 4-hydroxy-alprenolol in man. Life Sci. 1974 Feb 16;14(4):693–704. doi: 10.1016/0024-3205(74)90452-4. [DOI] [PubMed] [Google Scholar]
- Branch R. A., Herbert C. M., Read A. E. Determinants of serum antipyrine half-lives in patients with liver disease. Gut. 1973 Jul;14(7):569–573. doi: 10.1136/gut.14.7.569. [DOI] [PMC free article] [PubMed] [Google Scholar]
- Branch R. A., James J., Read A. E. A study of factors influencing drug disposition in chronic liver disease, using the model drug (+)-propranolol. Br J Clin Pharmacol. 1976 Apr;3(2):243–249. doi: 10.1111/j.1365-2125.1976.tb00599.x. [DOI] [PMC free article] [PubMed] [Google Scholar]
- Branch R. A., Shand D. G. Propranolol disposition in chronic liver disease: a physiological approach. Clin Pharmacokinet. 1976;1(4):264–279. doi: 10.2165/00003088-197601040-00002. [DOI] [PubMed] [Google Scholar]
- Ehrnebo M., Boréus L. O., Lönroth U. Bioavailability and first-pass metabolism of oral pentazocine in man. Clin Pharmacol Ther. 1977 Dec;22(6):888–892. doi: 10.1002/cpt1977226888. [DOI] [PubMed] [Google Scholar]
- Farmer J. B., Kennedy I., Levy G. P., Marshall R. J. Pharmacology of AH 5158; a drug which blocks both - and -adrenoceptors. Br J Pharmacol. 1972 Aug;45(4):660–675. doi: 10.1111/j.1476-5381.1972.tb08125.x. [DOI] [PMC free article] [PubMed] [Google Scholar]
- Groszmann R., Kotelanski B., Cohn J. N., Khatri I. M. Quantitation of portasystemic shunting from the splenic and mesenteric beds in alcoholic liver disease. Am J Med. 1972 Dec;53(6):715–722. doi: 10.1016/0002-9343(72)90188-x. [DOI] [PubMed] [Google Scholar]
- Joekes A. M., Thompson F. D. Acute haemodynamic effects of labetalol and its subsequent use of an oral hypotensive agent. Br J Clin Pharmacol. 1976 Aug;3(4 Suppl 3):789–793. [PubMed] [Google Scholar]
- Kornhauser D. M., Wood A. J., Vestal R. E., Wilkinson G. R., Branch R. A., Shand D. G. Biological determinants of propranolol disposition in man. Clin Pharmacol Ther. 1978 Feb;23(2):165–174. doi: 10.1002/cpt1978232165. [DOI] [PubMed] [Google Scholar]
- Levi A. J., Sherlock S., Walker D. Phenylbutazone and isoniazid metabolism in patients with liver disease in relation to previous drug therapy. Lancet. 1968 Jun 15;1(7555):1275–1279. doi: 10.1016/s0140-6736(68)92292-7. [DOI] [PubMed] [Google Scholar]
- Martin L. E., Hopkins R., Bland R. Metabolism of labetalol by animals and man. Br J Clin Pharmacol. 1976 Aug;3(4 Suppl 3):695–710. [PubMed] [Google Scholar]
- Richards D. A., Maconochie J. G., Bland R. E., Hopkins R., Woodings E. P., Martin L. E. Relationship between plasma concentrations and pharmacological effects of labetalol. Eur J Clin Pharmacol. 1977 Jan 3;11(2):85–90. doi: 10.1007/BF00562897. [DOI] [PubMed] [Google Scholar]
- Shand D. G. Pharmacokinetic properties of the beta-adrenergic receptor blocking drugs. Drugs. 1974;7(1):39–47. doi: 10.2165/00003495-197407010-00003. [DOI] [PubMed] [Google Scholar]
- Shand D. G., Rangno R. E. The disposition of propranolol. I. Elimination during oral absorption in man. Pharmacology. 1972;7(3):159–168. doi: 10.1159/000136285. [DOI] [PubMed] [Google Scholar]
