Skip to main content
PMC home page
British Journal of Clinical Pharmacology logoLink to British Journal of Clinical Pharmacology
. 1984 Jan;17(1):49–53. doi: 10.1111/j.1365-2125.1984.tb04998.x

Oxazepam pharmacokinetics in thyroid disease.

A K Scott, A S Khir, P D Bewsher, G M Hawksworth
PMCID: PMC1463289  PMID: 6419761

Abstract

The pharmacokinetics of oxazepam, a drug mainly eliminated by a single step glucuronidation reaction, were studied in seven hyperthyroid and six hypothyroid patients before and after treatment. Oxazepam elimination half-life was shorter and apparent oral clearance higher in untreated hyperthyroid patients than after treatment. There was no significant change in oxazepam elimination in hypothyroid subjects. Time to peak concentration (tmax) was reduced in the hyperthyroid state. Hypothyroidism had no significant effect on tmax. Serum bilirubin concentration was lower in the patients while hyperthyroid before treatment than when euthyroid and also lower than in the hypothyroid patients. There was no significant correlation between serum bilirubin concentrations and oxazepam elimination. These results suggest that glucuronyl transferase activity is increased in hyperthyroidism but is not altered in most patients with hypothyroidism. The extent of increase in glucuronyl transferase activity is similar to that produced by enzyme inducing drugs.

Full text

PDF
53

Selected References

These references are in PubMed. This may not be the complete list of references from this article.

  1. Bock K. W. Dual role of glucuronyl- and sulfotransferases converting xenobiotics into reactive or biologically inactive and easily excretable compounds. Arch Toxicol. 1977 Dec 30;39(1-2):77–85. doi: 10.1007/BF00343277. [DOI] [PubMed] [Google Scholar]
  2. Crooks J., Hedley A. J., Macnee C., Stevenson I. H. Proceedings: Changes in drug metabolizing ability in thyroid disease. Br J Pharmacol. 1973 Sep;49(1):156P–157P. [PMC free article] [PubMed] [Google Scholar]
  3. Das K. C., Mukherjee M., Sarkar T. K., Dash R. J., Rastogi G. K. Erythropoiesis and erythropoietin in hypo- and hyperthyroidism. J Clin Endocrinol Metab. 1975 Feb;40(2):211–220. doi: 10.1210/jcem-40-2-211. [DOI] [PubMed] [Google Scholar]
  4. Feely J., Stevenson I. H., Crooks J. Altered plasma protein binding of drugs in thyroid disease. Clin Pharmacokinet. 1981 Jul-Aug;6(4):298–305. doi: 10.2165/00003088-198106040-00004. [DOI] [PubMed] [Google Scholar]
  5. Forfar J. C., Pottage A., Toft A. D., Irvine W. J., Clements J. A., Prescott L. F. Paracetamol pharmacokinetics in thyroid disease. Eur J Clin Pharmacol. 1980 Oct;18(3):269–273. doi: 10.1007/BF00563010. [DOI] [PubMed] [Google Scholar]
  6. Kampmann J., Skovsted L. The kinetics of propylthiouracil in hyperthyroidism. Acta Pharmacol Toxicol (Copenh) 1975 Sep;37(3):201–210. doi: 10.1111/j.1600-0773.1975.tb00836.x. [DOI] [PubMed] [Google Scholar]
  7. Mølholm Hansen J., Skovsted L., Kampmann J. P., Lumholtz B. I., Siersbaek-Nielsen K. Unaltered metabolism of phenytoin in thyroid disorders. Acta Pharmacol Toxicol (Copenh) 1978 May;42(5):343–346. doi: 10.1111/j.1600-0773.1978.tb02214.x. [DOI] [PubMed] [Google Scholar]
  8. Patwardhan R. V., Yarborough G. W., Desmond P. V., Johnson R. F., Schenker S., Speeg K. V., Jr Cimetidine spares the glucuronidation of lorazepam and oxazepam. Gastroenterology. 1980 Nov;79(5 Pt 1):912–916. [PubMed] [Google Scholar]
  9. Scott A. K., Khir A. S., Steele W. H., Hawksworth G. M., Petrie J. C. Oxazepam pharmacokinetics in patients with epilepsy treated long-term with phenytoin alone or in combination with phenobarbitone. Br J Clin Pharmacol. 1983 Oct;16(4):441–444. doi: 10.1111/j.1365-2125.1983.tb02193.x. [DOI] [PMC free article] [PubMed] [Google Scholar]
  10. Shenfield G. M. Influence of thyroid dysfunction on drug pharmacokinetics. Clin Pharmacokinet. 1981 Jul-Aug;6(4):275–297. doi: 10.2165/00003088-198106040-00003. [DOI] [PubMed] [Google Scholar]
  11. Thomas F. B., Caldwell J. H., Greenberger N. J. Steatorrhea in thyrotoxicosis. Relation to hypermotility and excessive dietary fat. Ann Intern Med. 1973 May;78(5):669–675. doi: 10.7326/0003-4819-78-5-669. [DOI] [PubMed] [Google Scholar]
  12. Vesell E. S., Shapiro J. R., Passananti T., Jorgensen H., Shively C. A. Altered plasma half-lives of antipyrine, propylthiouracil, and methimazole in thyroid dysfunction. Clin Pharmacol Ther. 1975 Jan;17(1):48–56. doi: 10.1002/cpt197517148. [DOI] [PubMed] [Google Scholar]
  13. Watkins J. B., Gregus Z., Thompson T. N., Klaassen C. D. Induction studies on the functional heterogeneity of rat liver UDP-glucuronosyltransferases. Toxicol Appl Pharmacol. 1982 Jul;64(3):439–446. doi: 10.1016/0041-008x(82)90240-x. [DOI] [PubMed] [Google Scholar]
  14. 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]

Articles from British Journal of Clinical Pharmacology are provided here courtesy of British Pharmacological Society

RESOURCES