Oxymorphone hydrochloride, a potent opioid analgesic, is not carcinogenic in rats or mice

Toxicological Sciences

Volumn 96, Issue 1, 2007, Pages 162-173

  Shuey, Dana L ^a   Woodland, Cindy ^b   Tremblay, Claudine ^b   Gregson, Richard ^b   Gerson, Ronald J ^a  

^a ENDO PHARMACEUTICALS INC   (United States)

^b CHARLES RIVER LABORATORIES   (United States)

Author keywords

Analgesics; Carcinogenicity; Opioids

Indexed keywords

OPIATE; OXYMORPHONE;

ANIMAL EXPERIMENT; ANIMAL MODEL; ANIMAL TISSUE; AREA UNDER THE CURVE; ARTICLE; BLOOD TOXICITY; CONTROLLED STUDY; DRUG ABSORPTION; DRUG BLOOD LEVEL; DRUG CARCINOGENICITY; DRUG ELIMINATION; DRUG HALF LIFE; DRUG MEGADOSE; DRUG SAFETY; EYE TOXICITY; EYELID REFLEX; FEMALE; LUNG TOXICITY; MALE; MOUSE; MYDRIASIS; NEPHROTOXICITY; NONHUMAN; OBSTRUCTIVE UROPATHY; RAT; SEX DIFFERENCE; SURVIVAL RATE; TIME TO MAXIMUM PLASMA CONCENTRATION; TOXICOKINETICS; TOXIN ANALYSIS; URINE RETENTION; WEIGHT GAIN; WEIGHT REDUCTION;

ANALGESICS, OPIOID; ANIMALS; BODY WEIGHT; CARCINOGENICITY TESTS; CARCINOGENS; DOSE-RESPONSE RELATIONSHIP, DRUG; EATING; EYE; FEMALE; HUMANS; LEUKOCYTE COUNT; LUNG; MALE; MICE; OXYMORPHONE; RATS; RATS, SPRAGUE-DAWLEY; TIME FACTORS; TOXICITY TESTS, CHRONIC; UROGENITAL SYSTEM;

ANIMALIA; MUS; RATTUS;

EID: 33847304650     PISSN: 10966080     EISSN: 10960929     Source Type: Journal    
DOI: 10.1093/toxsci/kfl178     Document Type: Article

References (37)

1. Adams, M.P., and Ahdieh, H. (2004). Pharmacokinetics and dose-proportionality of oxymorphone extended release and its metabolites: Results of a randomized crossover study. Pharmacotherapy 24, 468-476.
2. Asanami, S., and Shimono, K. (1997). High body temperature induces micronuclei in mouse bone marrow. Mutat. Res. 390, 79-83.
3. Bryant, H. U., Bernton, E. W., and Holaday, J. W. (1987). Immunosuppressive effects of chronic morphine treatment in mice. Life Sci. 41, 1731-1738.
4. Craft, R. M., Stratmann, J. A., Bartok, R. E., Walpole, T. I., and King, S. J. (1999). Sex differences in development of morphine tolerance and dependence in the rat. Psychopharmacology 143, 1-7.
5. Das, R. K., and Swain, N. (1982). Mutagenic evaluation of morphine sulfate and pethidine hydrochloride in mice by the micronucleus test. Indian J. Med. Res. 75, 112-117.
6. Dunn, O. J. (1964). Multiple comparisons using rank sums. Technometrics 6, 241-256.
7. Falek, A., Jordan, R. B., King, B. J., Arnold, P. J., and Skelton, W. D. (1972). Human chromosomes and opiates. Arch. Gen. Psychiatry 27, 511-515.
8. Gutstein, H. B., and Akil, H. (2001). Opioid Analgesics. In Goodman & Gilman's The Pharmacologic Basis of Therapeutics, 10th ed. (J. G. Hardman, L. E. Limbird, A. G. Gilman, Eds.), pp. 569-619. McGraw-Hill, New York, NY.
9. Hall, J. A., Magne, M. L., and Twedt, D. C. (1987). Effect of acepromazine, diazepam, fentanyl-dorperidol, and oxymorphone on gastroesophageal sphincter pressure in healthy dogs. Am. J. Vet. Res. 48, 556-557.
10. International Conference on Harmonization (ICH). (1995). S1C: Guideline for industry. Dose selection for carcinogenicity studies of pharmaceuticals. Fed. Regist. 60, 11277-11281. Available at: http://www.fda.gov/cder/guidance/ichs1c.pdf.
11. Kamei, J. (1996). Role of opioidergic and serotonergic mechanisms in cough and antitussives. Pulm. Pharmacol. 9, 349-356.
12. Kamenetsky S., Rabinowitz, R., Urca, G., and Korczyn, A. D. (1997). Neuroanatomical aspects of mydriatic action of morphine in rats. J. Ocul. Pharmacol. Ther. 13, 405-413.
13. Keenan, K. P., Ballam, G. C., Soper, K. A., Laroque, P., Coleman, J. B., and Dixit, R. (1999). Diet, caloric restriction, and the rodent bioassay. Toxicol. Sci. 52(Suppl.), 24-34.
14. Kest, B., Palmese, C., and Hopkins, E. (2000). A comparison of morphine analgesic tolerance in male and female mice. Brain Res. 879, 17-22.
15. LeVier, D. G., McCay, J. A., Stern, M. L., Harris, L. S., Page, D., Brown, R. D., Musgrove, D. L., Butterworth, L. F., White, K. L., Jr, and Munson, A. E. (1994). Immunotoxicological profile of morphine sulfate in B6C3F1 females mice. Fundam. Appl. Toxicol. 22, 525-542.
16. Lin, K. K., and Rahman, M. A. (1998). Overall false positive rates in tests for linear trend in tumor incidence in animal carcinogenicity studies of new drugs. J. Biopharm. Stat. 8, 1-15.
17. Ling, G. S., Paul, D., Simantov, R., and Pasternak, G. W. (1989). Differential development of acute tolerance to analgesia, respiratory depression, gastrointestinal transit and hormone release in a morphine infusion model. Life Sci. 45, 1627-1636.
18. Mas, M., Sabater, E., Olaso, M. J., Horga, J. F., and Faura, C. C. (2000). Genetic variability in morphine sensitivity and tolerance between different strains of rats. Brain Res. 866, 109-115.
19. Mucha, R. F., Kalant, H., and Kim, C. (1987). Tolerance to hyperthermia produced by morphine in rat. Psychopharmacology 92, 452-458.
20. National Research Council. (1996). Guide for the care and use of laboratory animals. National Academy Press, Washington, DC.
21. National Toxicology Program. (1996). NTP toxicology and carcinogenesis studies of codeine (CAS No. 76-57-3) in F344 rats and B6C3F1 mice (feed studies). Natl. Toxicol. Program Tech. Rep. Ser. 455, 1-275.
22. National Toxicology Program. (1997). Effect of dietary restriction on toxicology and carcinogenesis studies in F344/N rats and B6C3F1 mice. Natl. Toxicol. Program Tech. Rep. Ser. 460, 1-411.
23. Peckham, E. M., and Traynor, J. R. (2006).Comparison of the antinociceptive response to morphine and morphine-like compounds in male and female Sprague-Dawley rats. J. Pharmacol. Exp. Ther. 316, 1195-1201.
24. Peto, R., Pike, M. C., Day, N. E., Gray, R. G., Lee, P. N., Parish, S., Peto, J., Richards, S., and Wahrendorf, J. (2000). Guidelines for simple, sensitive significance tests for carcinogenic effects in long-term animal experiments. In Long-term and Short-Term Screening Assays for Carcinogens: A Critical Appraisal. IARC Monographs, Supplement 2, pp. 311-426. IARC, Lyon, France.
25. Reisine, T., and Pasternak, G. (1996). Opioid Analgesics and Antagonists. In Goodman & Gilman's The Pharmacologic Basis of Therapeutics, 9th ed. (J. G. Hardman, L. E. Limbird, P. B. Molinoff, R. W. Ruddon, A. G. Gilman, Eds.), pp. 521-556. McGraw-Hill, New York, NY.
26. Roerig, S. C., and Fujimoto, J. M. (1988). Morphine antinociception in different strains of mice: Relationship of supraspinal-spinal multiplicative interactions to tolerance. J. Pharmacol. Exp. Ther. 247, 603-608.
27. Rosenkrantz, H., and Fleischman, R. W. (1988a). In vivo carcinogenesis assay of dl-methadone HCl in rodents. Fundam. Appl. Toxicol. 11, 640-651.
28. Rosenkrantz, H., and Fleischman, R.W. (1988b). In vivo carcinogenesis assay of L-α-acetylmethadol HCl in rodents. Fundam. Appl. Toxicol. 11, 626-639.
29. Sawant, S. G., and Couch, D. B. (1995). Induction of micronuclei in murine lymphocytes by morphine. Environ. Mol. Mutagen. 25, 279-283.
30. Shuey, D. L., Gudi, R., Krsmanovic, L., and Gerson, R. J. (2006). Evidence that oxymorphone-induced increases in micronuclei occur secondary to hyperthermia. Toxicol. Sci. 10.1093/toxsci/kfl148.
31. Solomon, R. E., Wasserman, E. A., and Gebhart, G. F. (1987). Tolerance to antinociceptive effects of morphine without tolerance to its effects on schedule-controlled behavior. Psychopharmacology 92, 327-333.
32. Swain, N., Das, R. K., and Paul, M. (1980). Cytogenetic assay of potential mutagenicity in vivo of two narcotic analgesics. Mutat. Res. 78, 97-100.
33. Tarone, R. E. (1975). Tests for trend in life table analysis. Biometrika 62, 679-682.
34. U.S. Food and Drug Administration (U.S. FDA). (2001). Guidance for industry: Statistical aspects of the design, analysis, and interpretation of chronic rodent carcinogenicity studies of pharmaceuticals (Draft guidelines). U.S. Department of Health and Human Services, Food and Drug Administration, Center for Drug Evaluation and Research (CDER).
35. U.S. Food and Drug Administration (U.S. FDA). (1997). Guidance for industry: Statistical aspects of design, analysis, and interpretation of animal carcinogenicity studies. (Draft guidelines). U.S. Department of Health and Human Services, Food and Drug Administration, Center for Drug Evaluation and Research (CDER).
36. West, J. P., Lysle, D. T., and Dykstra, L. A. (1997). Tolerance development to morphine-induced alterations of immune status. Drug Alcohol Depend. 46, 147-157.
37. Yoshitomi, K., and Boorman, A. G. (1990). Eye and associated glands. In Pathology of the Fischer Rat, 1st ed. (G. A. Boorman, S. L. Eustis, M. R. Elwell, C. Montgomery. Eds.), pp. 247. Academic Press, San Diego, CA.