BACKGROUND: Previous investigations reported no teratogenicity for methylphenidate (MPH). These studies investigated potential teratogenicity of d-MPH and d,l-MPH as commitments to the FDA. METHODS: Rabbits received 15, 50, 150 mg/kg/day (mkd) d-MPH or 20, 60, 200, 300 mkd d,l-MPH on gestation days 7-20. Rats received 2.5, 10, 40 mkd d-MPH, or 7, 25, 75, 80 mkd d,l-MPH on gestation days 6-17. RESULTS: d-MPH-In rabbits, mortality occurred at 150 mkd. Dilated pupils, increased activity, biting/chewing, respiration, and salivation occurred at >or=15 mkd in rabbits and >or=10 mkd in rats. Decreased food consumption occurred at 40 mkd in rats. Decreased body weight parameters occurred at 150 mkd in rabbits and >or=10 mkd in rats. There were no fetal findings in rabbits. In rats, skeletal variations occurred at 40 mkd. d,l-MPH-In rabbits, mortality occurred at >or=200 mkd. Dilated pupils, increased activity, biting/chewing, respiration, and salivation occurred at >or=20 mkd in rabbits and >or=25 mkd in rats. Decreased food consumption occurred at >or=200 mkd in rabbits and >or=25 mkd in rats. Decreased body weight parameters occurred at >or=200 mkd in rabbits and >or=25 mkd in rats. In rabbits, two fetuses (separate litters) had spina bifida and malrotated hindlimbs at 200 mkd. In rats, skeletal variations occurred at >or=75 mkd. CONCLUSIONS: There was no teratogenicity with d-MPH. There was a low teratogenic risk with d,l-MPH in only the rabbit. Higher C(max) may explain differences in results from previous studies. (c) 2008 Wiley-Liss, Inc.
BACKGROUND: Previous investigations reported no teratogenicity for methylphenidate (MPH). These studies investigated potential teratogenicity of d-MPH and d,l-MPH as commitments to the FDA. METHODS:Rabbits received 15, 50, 150 mg/kg/day (mkd) d-MPH or 20, 60, 200, 300 mkd d,l-MPH on gestation days 7-20. Rats received 2.5, 10, 40 mkd d-MPH, or 7, 25, 75, 80 mkd d,l-MPH on gestation days 6-17. RESULTS: d-MPH-In rabbits, mortality occurred at 150 mkd. Dilated pupils, increased activity, biting/chewing, respiration, and salivation occurred at >or=15 mkd in rabbits and >or=10 mkd in rats. Decreased food consumption occurred at 40 mkd in rats. Decreased body weight parameters occurred at 150 mkd in rabbits and >or=10 mkd in rats. There were no fetal findings in rabbits. In rats, skeletal variations occurred at 40 mkd. d,l-MPH-In rabbits, mortality occurred at >or=200 mkd. Dilated pupils, increased activity, biting/chewing, respiration, and salivation occurred at >or=20 mkd in rabbits and >or=25 mkd in rats. Decreased food consumption occurred at >or=200 mkd in rabbits and >or=25 mkd in rats. Decreased body weight parameters occurred at >or=200 mkd in rabbits and >or=25 mkd in rats. In rabbits, two fetuses (separate litters) had spina bifida and malrotated hindlimbs at 200 mkd. In rats, skeletal variations occurred at >or=75 mkd. CONCLUSIONS: There was no teratogenicity with d-MPH. There was a low teratogenic risk with d,l-MPH in only the rabbit. Higher C(max) may explain differences in results from previous studies. (c) 2008 Wiley-Liss, Inc.
Authors: Krista F Huybrechts; Gabriella Bröms; Lotte Brix Christensen; Kristjana Einarsdóttir; Anders Engeland; Kari Furu; Mika Gissler; Sonia Hernandez-Diaz; Pär Karlsson; Øystein Karlstad; Helle Kieler; Anna-Maria Lahesmaa-Korpinen; Helen Mogun; Mette Nørgaard; Johan Reutfors; Henrik Toft Sørensen; Helga Zoega; Brian T Bateman Journal: JAMA Psychiatry Date: 2018-02-01 Impact factor: 21.596
Authors: Lin Li; Ayesha C Sujan; Agnieszka Butwicka; Zheng Chang; Samuele Cortese; Patrick Quinn; Alexander Viktorin; A Sara Öberg; Brian M D'Onofrio; Henrik Larsson Journal: CNS Drugs Date: 2020-07 Impact factor: 5.749