The perinatal and postnatal toxicity of D-methylphenidate and D,L-methylphenidate in rats.
D-methylphenidate is an enantiomer of D,L-methylphenidate and was developed as an improved treatment for attention deficit hyperactivity disorder (ADHD) in children. The current study was performed to assess the potential perinatal and postnatal toxicity of both compounds in rats. About 125 presumed pregnant rats were assigned to five dose groups of 25 each. They were dosed with 2, 6, and 20 mg/kg/day D-methylphenidate and 40 mg/kg/day D,L-methylphenidate from gestation Day 7 to lactation Day 20. F1 generation rats were rebred to produce F2 fetuses. Various perinatal and postnatal measurements were made for the F0 and F1 rats. Among the significant findings were a reduction in maternal body weight gain for 20 mg/kg/day D-methylphenidate and D,L-methylphenidate and increased incidences of dilated pupil and vocalization for D,L-methylphenidate during the gestation period. Neither compound produced any other significant adverse findings in F0 and F1 generation rats at doses that were at least 25 times the maximum daily human therapeutic dose.
Teo
Steve K
SK
Celgene Corporation,7 Powder Horn Drive, Warren, NJ 07059, USA. steo@celgene.com
Stirling
David I
DI
Thomas
Steve D
SD
Hoberman
Alan M
AM
Christian
Mildred S
MS
Khetani
Vikram D
VD
D000818:Animals; D000831:Animals, Newborn; D001835:Body Weight / Q000187:drug effects; D000697:Central Nervous System Stimulants / Q000008:administration & dosage / Q000633:toxicity*; D004305:Dose-Response Relationship, Drug; D005314:Embryonic and Fetal Development / Q000187:drug effects*; D005260:Female; D008297:Male; D008774:Methylphenidate / Q000008:administration & dosage / Q000633:toxicity*; D011247:Pregnancy; D011680:Pupil / Q000187:drug effects; D051381:Rats; D017207:Rats, Sprague-Dawley; D012098:Reproduction / Q000187:drug effects*; D013237:Stereoisomerism; D018675:Toxicity Tests; D014828:Vocalization, Animal / Q000187:drug effects
D000697:Central Nervous System Stimulants; D008774:Methylphenidate