D-Methylphenidate is non-genotoxic in in vitro and in vivo assays

Mutation Research - Genetic Toxicology and Environmental Mutagenesis

Volumn 537, Issue 1, 2003, Pages 67-79

  Teo, Steve K ^a   San, Richard H ^b   Wagner, Valentine O ^b   Gudi, Ramadevi ^b   Stirling, David I ^a   Thomas, Steve D ^a   Khetani, Vikram D ^a  

^a CELGENE CORPORATION   (United States)

^b BioReliance   (United States)

Author keywords

Attention deficit hyperactivity disorder; D MPH; Dexmethylphenidate; Enantiomer; Genetic toxicity; Genotoxicity; Methylphenidate

Indexed keywords

DEXMETHYLPHENIDATE; METHYLPHENIDATE;

ANIMAL CELL; ARTICLE; BACTERIAL MUTATION; BONE MARROW; CANCER RISK; CARCINOGENICITY; CONTROLLED STUDY; DRUG SCREENING; ENANTIOMER; EPIDEMIOLOGICAL DATA; FEMALE; GENOTOXICITY; IN VITRO STUDY; IN VIVO STUDY; LYMPHOMA; MALE; MICRONUCLEUS; MUTAGENICITY; NONHUMAN; PRIORITY JOURNAL; REVERTANT; TOXICITY; TUMOR CELL LINE;

BACTERIA (MICROORGANISMS); MAMMALIA;

EID: 0038057931     PISSN: 13835718     EISSN: None     Source Type: Journal    
DOI: 10.1016/S1383-5718(03)00053-6     Document Type: Article

References (31)

1. Kimko H., Cross J., Abernethy D. Pharmacokinetics and clinical effectiveness of methylphenidate. Clin. Pharmacokinet. 37:1999;45-70.
2. Sunohara G., Malone M., Rovet J., Humphries T., Roberts W., Taylor M. Effect of methylphenidate on attention in children with attention deficit hyperactivity disorder (ADHD): ERP evidence. Neuropsychopharmacology. 21:1999;218-228.
3. Zuddas A., Anciletta B., Muglia P., Cianchetti C. Attention-deficit/hyperactivity disorder: a neuropsychiatric disorder with childhood onset. Eur. J. Paediatr. Neurol. 4:2000;53-62.
4. Schachter H., Pham B., King J., Langford S., Moher D. How efficacious and safe is short-acting methylphenidate for the treatment of attention-deficit disorder in children and adolescents? A meta analysis. Can. Med. Assoc. J. 165:2001;1475-1488.
5. G. Weiss, L. Hechtman, Hyperactive Children Grown Up: ADHD in Children. Adolescents and Adults, second ed., The Guilford Press, 1984.
6. K. Patrick, R. Muller, C. Gualtieri, G. Breese, Pharmacokinetics and actions of methylphenidate. In: H. Meltzer (Ed.), Psychopharmacology: The Third Generation of Progress, Raven, New York, 1987, pp. 1387-1395.
7. Szporny L., Gorog P. Investigations into the correlations between monoamine oxidase inhibition and other effects due to methylphenidate and its stereoisomers. Biochem. Pharmacol. 8:1961;263-268.
8. L. Greenhill, Pharmacologic treatment of attention deficit hyperactivity disorder. In: D. Shaffer (Ed.), The Psychiatric Clinics of North America, vol. 15, #1, Harcourt Brace, Jovanovich, 1991, pp. 1-7.
9. Luthman J., Fredriksson A., Lewander T., Jonsson G., Archer T. Effects of D-amphetamine and methylphenidate on hyperactivity produced by neonatal 6-hydroxydopamine treatment. Psychopharmacology. 99:1989;550-557.
10. Patrick K., Caldwell R., Ferris R., Breese G. Pharmacology of the enantiomers of threo-methylphenidate. J. Pharmacol. Exp. Ther. 241:1987;152-158.
11. Ding Y., Fowler J., Volkow N., Logan J., Gatley S., Sugano Y. Carbon-11-D-threo-methylphenidate binding to dopamine transporter in baboon brain. J. Nuclear Med. 36:1995;2298-2305.
12. 11C )D-threo and L-threo-methylphenidate in the human and baboon brain Psychopharmacology. 131:1997;71-78.
13. Toxicology and carcinogenesis studies of methylphendiate hydrochloride in F344/N rats and B6C3F1 mice, Public Health Service, NIH, NTP TR, vol. 439, 1995.
14. S. Galloway, M. Armstrong, C. Reuben, S. Colman, B. Brown, C. Cannon, A. Bloom, F. Nakamura, M. Ahmed, S. Duk, J. Rimpo, B. Margolin, M. Resnick, B. Anderson, E. Zeiger, Chromosome aberrations and sister chromatid exchanges in Chinese hamster ovary cells: evaluations of 108 chemicals, Environ. Mol. Mutagen, Suppl. 10 (1987) 1-175.
15. ICH Guidance for Industry, S2A genotoxicity: specific aspects of regulatory tests for pharmaceuticals, Fed. Reg. 61 (1996) 18191-18202.
16. ICH Guidance for Industry, S2B genotoxicity: a standard battery for genotoxicity testing of pharmaceuticals, Fed. Reg. 62 (1997) 21152-21160.
17. Maron D., Ames B. Revised methods for the Salmonella mutagenicity test. Mutat. Res. 113:1983;173-215.
18. +/- mouse lymphoma cells. Mutat. Res. 31:1975;17-29.
19. Hayashi M., Tice R., MacGregor J., Anderson D., Blakey D., Dirsch-Volders M., Oleson F. Jr., Pacchierotti F., Romagna F., Shimada H., Sutou S., Vannier B. In vivo rodent erythrocyte micronucleus assay. Mutat. Res. 312:1994;293-304.
20. Mavournin K., Blakey D., Cimino M., Salamone M., Heddle J. The in vivo micronucleus assay in mammalian bone marrow and peripheral blood. A report of the US Environemtnal Protection Agency Gene-Tox Program. Mutat. Res. 239:1990;29-80.
21. Kastenbaum M., Bowman K. Tables for determining the statistical significance of mutation frequencies. Mutat. Res. 9:1970;527-549.
22. S. Teo, D. Stirling, A. Hoberman, M. Christian, S. Thomas, V. Khetani, D-Methylphenidate and D,L-methylphenidate are not developmental toxicants in rats and rabbits, Teratology, 2003, in press.
23. R. Diener, Toxicology of ritalin, In: B. Osman, L. Greenhill (Eds.), Ritalin, Theory and Patient Management, Mary Ann Liebert Inc., 1991, pp. 35-43.
24. S. Teo, D. Stirling, S. Thomas, J. Noveroske, V. Khetani, A 90-day oral gavage toxicity study of D-methylphenidate and D,L-methylphenidate in Beagle dogs. Int. J. Toxicol., 2003, in press.
25. Teo S., Stirling D., Thomas S., Kiorpes A., Khetani V. A 90-day oral gavage toxicity study of D-methylphenidate and D,L-methylphenidate in Sprague-Dawley rats. Toxicology. 179:2002;183-190.
26. Larez A., Briceno E., Ochoa Y., Montenegro M., Aponte N. Mutagenicity obtained experimentally by oral administration of dextroamphetamine sulphate to the rat. Bull. Narc. 31:1979;67-70.
27. Agarwal K., Mukherjee A., Sharma A., Sharma R., Bhardwaj K., Sen S. Clastogenic effect of fenfluramine in mice bone marrow cells in vivo. Environ. Mol. Mutagen. 19:1992;323-326.
28. Dunnick J., Hailey J. Experimental studies on the long-term effects of methylphenidate hydrochloride. Toxicology. 103:1995;77-84.
29. Novartis internal document.
30. Toxicology and carcinogenesis studies of D,L-amphetamine sulfate in F344/N rats and B6C3F1 mice, Public Health Service, NIH, NTP TR, vol. 387, 1991.
31. Selby J., Friedman G., Fireman B. Screening prescription drugs for possible carcinogenicity: eleven to fifteen years of follow-up. Cancer Res. 49:1989;5737-5747.