Impairment of Hepatic Drug Oxidation by Propoxyphene
Authors: Darrell R. Abernethy, David J. Greenblatt, Knight Steel, Richard I. Shader
Journal: Annals of Internal Medicine (1982)

Brief Reports1 August 1982Impairment of Hepatic Drug Oxidation by PropoxypheneDARRELL R. ABERNETHY, M.D., Ph.D., DAVID J. GREENBLATT, M.D., KNIGHT STEEL, M.D., RICHARD I. SHADER, M.D.DARRELL R. ABERNETHY, M.D., Ph.D.Search for more papers by this author, DAVID J. GREENBLATT, M.D.Search for more papers by this author, KNIGHT STEEL, M.D.Search for more papers by this author, RICHARD I. SHADER, M.D.Search for more papers by this authorAuthor, Article, and Disclosure Informationhttps://doi.org/10.7326/0003-4819-97-2-223 SectionsAboutPDF ToolsAdd to favoritesDownload CitationsTrack CitationsPermissions ShareFacebookTwitterLinkedInRedditEmail ExcerptPropoxyphene, a widely used analgesic, may act synergistically with other centrally active drugs resulting in unexpectedly severe or sometimes fatal central nervous system depression (1). The mechanism of such an interaction has not been defined. In-vitro data suggest inhibition of cytochrome P-450 hepatic oxidative drug metabolism by propoxyphene (2), but conclusive in-vivo data showing propoxyphene impairment of human oxidative drug metabolism are not reported.We report a doxepin-treated patient whose doxepin plasma levels were monitored before and during propoxyphene therapy. The pharmacokinetic interaction was further assessed by a study of antipyrine metabolism, used as a marker for drug oxidation (3),...References1. WETLI C and BEDNARCZYK L. Deaths related to propoxyphene overdose: A ten-year assessment. South Med J. 1980;73:1205-9. CrossrefMedlineGoogle Scholar2. PETERSON G, HOSTETLER R, LEHMAN T, and COVAULT H. Acute inhibition of oxidative drug metabolism by propoxyphene (Darvon). Biochem Pharmacol. 1979;28:1783-9. CrossrefMedlineGoogle Scholar3. VESELL E. The antipyrine test in clinical pharmacology: conceptions and misconceptions. Clin Pharmacol Ther. 1979;26:275-86. CrossrefMedlineGoogle Scholar4. ABERNETHY D, GREENBLATT D, and SHADER R. Tricyclic antidepressant determination in human plasma by gas-liquid chromatography using nitrogen-phosphorous detection: Application to single-dose pharmacokinetic studies. Pharmacology. 1981;23:57-63. CrossrefMedlineGoogle Scholar5. BRODIE B, AXELROD J, SOBERMAN R, and LEVY B. The estimation of antipyrine in biological materials. J Biol Chem. 1949;179:25-9. CrossrefMedlineGoogle Scholar6. ABERNETHY D, GREENBLATT D, and ZUMBO A. Antipyrine determination in human plasma by gas-liquid chromatography using nitrogenphosphorous detection. J Chromatogr. 1981;223:432-7. CrossrefMedlineGoogle Scholar7. GREENBLATT D and KOCH-WESER J. Clinical pharmacokinetics. N Engl J Med. 1975;293:702-5, 964-70. CrossrefMedlineGoogle Scholar8. KUTT H. Biochemical and genetic factors regulating dilantin metabolism in man. Ann NY Acad Sci. 1971;179:704-22. CrossrefGoogle Scholar9. DAM M, KRISTENSEN C, HANSEN B, and CHRISTIANSEN J. Interaction between carbamazepine and propoxyphene in man. Acta Neurol Scand. 1979;56:603-7. CrossrefGoogle Scholar10. HANSEN B, DAM M, and BRANDT J. Influence of dextropropoxyphene on steady state serum levels and protein binding of three anti-epileptic drugs in man. Acta Neurol Scand. 1980;61:357-67. CrossrefMedlineGoogle Scholar This content is PDF only. To continue reading please click on the PDF icon. Author, Article, and Disclosure InformationAuthors: DARRELL R. ABERNETHY, M.D., Ph.D.; DAVID J. GREENBLATT, M.D.; KNIGHT STEEL, M.D.; RICHARD I. SHADER, M.D.Affiliations: Tufts University School of Medicine New England Medical Center Hospital Boston University School of Medicine Jewish Memorial Hospital Boston, Massachusetts PreviousarticleNextarticle Advertisement FiguresReferencesRelatedDetails Metrics Cited byDRUG–DRUG INTERACTIONS IN PEDIATRIC PSYCHOPHARMACOLOGYOpioid Drug-Drug Interactions: A ReviewCatastrophic neurologic signs due to drug interaction: Tegretol and darvonThe basis for variability of response to anti-rheumatic drugsPsychotropic Drug Interactions in the Patient with Late-Onset Depression or PsychosisDextropropoxyphene OverdoseBenzodiazepines: selective administrationAltered distribution of debrisoquine oxidation phenotypes in patients with systemic lupus erythematosusUpdate of cardiovascular drug interactionsInteraction of propoxyphene with diazepam, alprazolam and lorazepam.Opioid analgesics and narcotic antagonistsIbuprofen Does Not Impair Antipyrine Clearance 1 August 1982Volume 97, Issue 2Page: 223-224KeywordsAnalgesicsCentral nervous systemClinical pharmacologyDrug interactionsDrug metabolismDrugsGeriatricsHospital medicineMedical servicesPharmacokinetics ePublished: 1 December 2008 Issue Published: 1 August 1982 PDF downloadLoading ...