Abstract
The EEG response and drug kinetics after intravenous infusion of diazepam at 1-0 mg/min until nystagmus, dysarthria, and moderate sedation developed, has been investigated in five normal subjects and 17 patients with chronic liver disease. Diazepam induced adequate premedication with a similar clinical response in all subjects with no adverse reactions. Maximal response was during or within five minutes of infusion. The dose of diazepam required in liver chronic disease was 17-9 +/- 1-4 mg (M +/- SEM) compared with 27 +/- 5-4 mg in controls (p less than 0-01). Dose correlated significantly with serum albumin (p less than 0-05). Baseline mean dominant frequency (MDF) and slow wave index (SWI) significantly correlated with albumin (p less than 0-01). After diazepam, the MDF decreased and SWI increased. The change was greatest at the time of maximal clinical response. It was greater in liverdisease and was greatest in patients with previous hepaticencephalopathy. In spite of reduced dose requirements in liver disease, there was no significant difference in plasma concentration at the end of drug infusion...
Full text
PDFSelected References
These references are in PubMed. This may not be the complete list of references from this article.
- Andreasen P. B., Ranek L., Statland B. E., Tygstrup N. Clearance of antipyrine-dependence of quantitative liver function. Eur J Clin Invest. 1974 Apr;4(2):129–134. doi: 10.1111/j.1365-2362.1974.tb00383.x. [DOI] [PubMed] [Google Scholar]
- BICKFORD R. G., BUTT H. R. Hepatic coma: the electroencephalographic pattern. J Clin Invest. 1955 Jun;34(6):790–799. doi: 10.1172/JCI103134. [DOI] [PMC free article] [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]
- CAESAR J., SHALDON S., CHIANDUSSI L., GUEVARA L., SHERLOCK S. The use of indocyanine green in the measurement of hepatic blood flow and as a test of hepatic function. Clin Sci. 1961 Aug;21:43–57. [PubMed] [Google Scholar]
- De Silva J. A., Koechlin B. A., Bader G. Blood level distribution patterns of diazepam and its major metabolite in man. J Pharm Sci. 1966 Jul;55(7):692–702. doi: 10.1002/jps.2600550706. [DOI] [PubMed] [Google Scholar]
- Fischer J. E., Baldessarini R. J. False neurotransmitters and hepatic failure. Lancet. 1971 Jul 10;2(7715):75–80. doi: 10.1016/s0140-6736(71)92048-4. [DOI] [PubMed] [Google Scholar]
- Klotz U., Avant G. R., Hoyumpa A., Schenker S., Wilkinson G. R. The effects of age and liver disease on the disposition and elimination of diazepam in adult man. J Clin Invest. 1975 Feb;55(2):347–359. doi: 10.1172/JCI107938. [DOI] [PMC free article] [PubMed] [Google Scholar]
- LAIDLAW J., READ A. E. The E.E.G. in hepatic encephalopathy. Clin Sci. 1963 Feb;24:109–120. [PubMed] [Google Scholar]
- LAIDLAW J., READ A. E. The electroencephalographic diagnosis of manifest and latent 'delirium' with particular reference to that complicating hepatic cirrhosis. J Neurol Neurosurg Psychiatry. 1961 Feb;24:58–70. doi: 10.1136/jnnp.24.1.58. [DOI] [PMC free article] [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]
- Marcucci F., Fanelli R., Mussini E., Garattini S. Further studies on species difference in diazepam metabolism. Eur J Pharmacol. 1970 Feb;9(2):253–256. doi: 10.1016/0014-2999(70)90308-0. [DOI] [PubMed] [Google Scholar]
- Mawer G. E., Miller N. E., Turnberg L. A. Metabolism of amylobarbitone in patients with chronic liver disease. Br J Pharmacol. 1972 Mar;44(3):549–560. doi: 10.1111/j.1476-5381.1972.tb07292.x. [DOI] [PMC free article] [PubMed] [Google Scholar]
- Morgan M. H., Bolton C. H., Morris J. S., Read A. E. Medium chain triglycerides and hepatic encephalopathy. Gut. 1974 Mar;15(3):180–184. doi: 10.1136/gut.15.3.180. [DOI] [PMC free article] [PubMed] [Google Scholar]
- Morgan M. H., Read A. E. Antidepressants and liver disease. Gut. 1972 Sep;13(9):697–701. doi: 10.1136/gut.13.9.697. [DOI] [PMC free article] [PubMed] [Google Scholar]
- Murray-Lyon I. M., Young J., Parkes J. D., Knill-Jones R. P., Williams R. Clinical and electroencephalographic assessment of diazepam in liver disease. Br Med J. 1971 Oct 30;4(5782):265–266. doi: 10.1136/bmj.4.5782.265. [DOI] [PMC free article] [PubMed] [Google Scholar]
- READ A. E., LAIDLAW J., HASLAM R. M., SHERLOCK S. Neuropsychiatric complications following chlorothiazide therapy in patients with hepatic cirrhosis: possible relation to hypokalaemia. Clin Sci. 1959 Aug;18:409–423. [PubMed] [Google Scholar]
- Read A. E., Laidlaw J., McCarthy C. F. Effects of chlorpromazine in patients with hepatic disease. Br Med J. 1969 Aug 30;3(5669):497–499. doi: 10.1136/bmj.3.5669.497. [DOI] [PMC free article] [PubMed] [Google Scholar]
- SHERLOCK S., SUMMERSKILL W. H., WHITE L. P., PHEAR E. A. Portal-systemic encephalopathy; neurological complications of liver disease. Lancet. 1954 Sep 4;267(6836):454–457. [PubMed] [Google Scholar]
- Schwartz M. A., Koechlin B. A., Postma E., Palmer S., Krol G. Metabolism of diazepam in rat, dog, and man. J Pharmacol Exp Ther. 1965 Sep;149(3):423–435. [PubMed] [Google Scholar]
- Shand D. G., Nuckolls E. M., Oates J. A. Plasma propranolol levels in adults with observations in four children. Clin Pharmacol Ther. 1970 Jan-Feb;11(1):112–120. doi: 10.1002/cpt1970111112. [DOI] [PubMed] [Google Scholar]
- van der Klejin E., van Rossum J. M., Muskens E. T., Rijntjes N. V. Pharmacokinetics of diazepam in dogs, mice and humans. Acta Pharmacol Toxicol (Copenh) 1971;29 (Suppl 3):109–127. doi: 10.1111/j.1600-0773.1971.tb03291.x. [DOI] [PubMed] [Google Scholar]