NDLI: Juvenile toxicity assessment of d,l-methylphenidate in rats.

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Juvenile toxicity assessment of d,l-methylphenidate in rats.

Content Provider	World Health Organization (WHO)-Global Index Medicus
Author	Beckman, David A. Schneider, Marilynn Youreneff, Maureen Tse, Francis L. S.
Description	Country affiliation: United States Author Affiliation: Beckman DA ( Safety Profiling & Assessment, Novartis Pharmaceuticals Corporation, East Hanover, New Jersey 07936, USA. david.beckman@novartis.com)
Abstract	BACKGROUND: The oral administration of d,l-methylphenidate (MPH) was designed to encompass the major part of postnatal development in the rat and to evaluate potential chronic effects. METHODS: Wistar Hannover rats were cross-fostered on postpartum day 0 (day of birth) and were administered MPH at doses of 5, 50, and 100 mg/kg/day (mpkd) on postpartum days 7 to 70. Clinical signs, body weight, food consumption, developmental, behavioral, clinical/anatomic pathology, toxicokinetic, and fertility evaluations were conducted. RESULTS: MPH-related effects on clinical signs, body weight, and behavior tests were noted. Increased locomotor activity and cage biting/chewing occurred at > or =5 mpkd (females) and > or =50 mpkd (males) and were absent after dosing ceased. Body weight parameters were decreased at > or =50 mpkd and were comparable to controls at 5 weeks' recovery. Open field motor activity tests conducted 2 weeks after dosing ceased revealed decreased peripheral beam breaks at > or =50 mpkd. Passive avoidance tests conducted 3 weeks after dosing ceased indicated decreased females reaching learning criterion at 100 mpkd. This is considered of nominal significance as there were no effects in the water maze test or retention in passive avoidance test. After multiple doses, females exhibited higher exposures than males and exposures were reduced in all groups in comparison to those after a single dose. CONCLUSIONS: These results suggest that MPH can produce enduring behavioral effects in rats. The no-toxicologic-effect-level was 5 mpkd, associated with AUC((0-24 h)) racemate values in males and females, respectively, of 101 and 153 ng.h/mL after chronic dosing.
File Format	HTM / HTML
ISSN	15429733
Issue Number	1
Volume Number	83
e-ISSN	15429741
Journal	Birth Defects Research Part B: Developmental and Reproductive Toxicology
Language	English
Publisher	Wiley
Publisher Date	2008-02-01
Publisher Place	United States
Access Restriction	Subscribed
Subject Keyword	Discipline Teratology Discipline Toxicology Behavior, Animal Drug Effects Central Nervous System Stimulants Toxicity Methylphenidate Animals Animals, Newborn Avoidance Learning Body Weight Dose-response Relationship, Drug Female Fertility Male Maze Learning Motor Activity No-observed-adverse-effect Level Rats Rats, Wistar Stereoisomerism Journal Article
Content Type	Text
Resource Type	Article
Subject	Developmental Biology Health, Toxicology and Mutagenesis Toxicology Embryology

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