Enantioselective pharmacokinetics and pharmacodynamics of dl-threo-methylphenidate in children with attention deficit hyperactivity disorder.
Nine boys with attention-deficit hyperactivity disorder took part in a study in which d-methylphenidate, l-methylphenidate, dl-methylphenidate, or placebo were administered in a double-blind, four-way, randomized, crossover design. Plasma levels of the isomers of methylphenidate were monitored by means of an enantioselective assay method. The ability of the children to perform tasks that required sustained attention was monitored by a battery of computer tests. There was no evidence of interconversion between the enantiomers in vivo, although the presence of the d-isomer significantly altered the pharmacokinetics of the l-antipode. The presence of the l-isomer did not affect the pharmacokinetics of d-methylphenidate. The computer tests revealed a drug-induced improvement in sustained attention that was entirely attributable to the d-enantiomer. There was no evidence to suggest that the effectiveness of d-methylphenidate was in any way compromised by the presence of its antipode.
Srinivas
N R
NR
College of Pharmacy, University of Saskatchewan, Saskatoon, Canada.
Hubbard
J W
JW
Quinn
D
D
Midha
K K
KK
D000704:Analysis of Variance; D001289:Attention Deficit Disorder with Hyperactivity / Q000188:drug therapy*; D002648:Child; D004311:Double-Blind Method; D006801:Humans; D008774:Methylphenidate / Q000493:pharmacokinetics / Q000627:therapeutic use*; D013237:Stereoisomerism
D008774:Methylphenidate