Abstract
1 The effect of intravenous administration of 100 units of heparin on plasma of diazepam, chlordiazepoxide, oxazepam and lorazepam was examined in fourteen normal subjects and five patients with cirrhosis. 2 In normal non-fasted subjects heparin caused a rapid 150--250% rise in the free fraction of diazepam, chlordiazepoxide and oxazepam but no change of lorazepam. The changes in free fraction were slightly smaller, but still significant, when the subjects were fasted. 3 These change in free fraction occurred within 90 s of administration of heparin and binding had returned to baseline by 30 to 45 min. 4 In the cirrhotic subjects the response to heparin was variable. 5 The use of heparin during drug disposition studies may affect the estimation of pharmacokinetic parameters and possibly pharmacological effects which are dependent on the circulating unbound drug level.
Full text
PDF
Selected References
These references are in PubMed. This may not be the complete list of references from this article.
- CHLOUVERAKIS C., HARRIS P. Nmn-esterified fatty acids and lipoprotein lipase activity in patients with cirrhosis of the liver. Gut. 1961 Sep;2:233–239. doi: 10.1136/gut.2.3.233. [DOI] [PMC free article] [PubMed] [Google Scholar]
- Gugler R., Shoeman D. W., Azarnoff D. L. Effect of in vivo elevation of free fatty acids on protein binding of drugs. Pharmacology. 1974;12(3):160–165. doi: 10.1159/000136534. [DOI] [PubMed] [Google Scholar]
- Holford N. H., Vozeh S., Coates P., Powell J. R., Thiercelin J. F., Upton R. More on heparin lock. N Engl J Med. 1977 Jun 2;296(22):1300–1301. doi: 10.1056/NEJM197706022962223. [DOI] [PubMed] [Google Scholar]
- Kessler K. M., Leech R. C., Spann J. F. Blood collection techniques, heparin and quinidine protein binding. Clin Pharmacol Ther. 1979 Feb;25(2):204–210. doi: 10.1002/cpt1979252204. [DOI] [PubMed] [Google Scholar]
- McQueen E. G., Wardell W. M. Drug displacement from protein binding: isolation of a redistributional drug interaction in vivo. Br J Pharmacol. 1971 Oct;43(2):312–324. [PMC free article] [PubMed] [Google Scholar]
- Oie S., Levy G. Effect of salicylic acid on pharmacokinetics of free and plasma protein-bound bilirubin in experimental unconjugated hyperbilirubinemia. J Pharm Sci. 1979 Jan;68(1):1–6. doi: 10.1002/jps.2600680105. [DOI] [PubMed] [Google Scholar]
- Olivecrona T., Hernell O., Egelrud T. Lipoprotein lipase. Adv Exp Med Biol. 1975;52:269–279. doi: 10.1007/978-1-4684-0946-8_24. [DOI] [PubMed] [Google Scholar]
- Rudman D., Bixler T. J., 2nd, Del Rio A. E. Effect of free fatty acids on binding of drugs by bovine serum albumin, by human serum albumin and by rabbit serum. J Pharmacol Exp Ther. 1971 Feb;176(2):261–272. [PubMed] [Google Scholar]
- Wilcox H. G., Dunn G. D., Schenker S. Plasma long chain fatty acids and esterified lipids in cirrhosis and hepatic encephalopathy. Am J Med Sci. 1978 Nov-Dec;276(3):293–303. doi: 10.1097/00000441-197811000-00006. [DOI] [PubMed] [Google Scholar]
- Wilkinson G. R., Shand D. G. Commentary: a physiological approach to hepatic drug clearance. Clin Pharmacol Ther. 1975 Oct;18(4):377–390. doi: 10.1002/cpt1975184377. [DOI] [PubMed] [Google Scholar]
- Wood M., Shand D. G., Wood A. J. Altered drug binding due to the use of indwelling heparinized cannulas (heparin lock) for sampling. Clin Pharmacol Ther. 1979 Jan;25(1):103–107. doi: 10.1002/cpt1979251103. [DOI] [PubMed] [Google Scholar]
- Wood M., Shand D. G., Wood A. J. Propranolol binding in plasma during cardiopulmonary bypass. Anesthesiology. 1979 Dec;51(6):512–516. doi: 10.1097/00000542-197912000-00006. [DOI] [PubMed] [Google Scholar]