Bioavailability of modified-release methylphenidate: influence of high-fat breakfast when administered intact and when capsule content sprinkled on applesauce.
Ritalin, an immediate release form of racemic methylphenidate hydrochloride, has been available in the USA since 1955 and is used for the treatment of ADHD. The objective of this study was to evaluate the pharmacokinetics of modified-release methylphenidate (highest single dose), Ritalin LA, when administered under fasting condition, with a high-fat breakfast, and when sprinkled on applesauce in healthy adult subjects. Blood samples were drawn for 24 h following a 40 mg oral administration. Most subjects appeared to produce a bimodal methylphenidate plasma concentration profile. In all three treatment groups, methylphenidate was rapidly absorbed with an initial average t(max(0-4)) of 1.3-2.4 h and an average peak plasma concentration [C(max(abs))] of 14.4-15.2 ng/ml. On average, both the rate [C(max(abs)) and t(max(abs))] and the extent of absorption (AUC(0- infinity)) of methylphenidate were similar when the capsule was given with a high fat breakfast and when the capsule contents were sprinkled onto applesauce, compared with the fasting state. No dose dumping was observed when the capsule was given with a high fat breakfast or when sprinkled onto applesauce. The dose was safe and generally well tolerated. Coadministration of a single oral dose of 40 mg methylphenidate capsule whether administered intact with a high-fat breakfast or sprinkled on applesauce did not affect the overall rate or extent of absorption of methylphenidate compared with the fasted condition.
Lee
Lucy
L
Novartis Pharmaceuticals, East Hanover, NJ 07936, USA. lucy.lee@pharma.novartis.com
Kepple
Joanne
J
Wang
Yibin
Y
Freestone
Stephen
S
Bakhtiar
Ray
R
Wang
Yanfeng
Y
Hossain
Mohammad
M
D000284:Administration, Oral; D000293:Adolescent; D000328:Adult; D019540:Area Under Curve; D001289:Attention Deficit Disorder with Hyperactivity / Q000188:drug therapy; D001682:Biological Availability; D002214:Capsules; D003692:Delayed-Action Preparations / Q000008:administration & dosage / Q000493:pharmacokinetics*; D004041:Dietary Fats / Q000008:administration & dosage / Q000493:pharmacokinetics*; D004305:Dose-Response Relationship, Drug; D004334:Drug Administration Schedule; D005260:Female; D005502:Food; D018565:Food-Drug Interactions / Q000502:physiology; D006801:Humans; D008297:Male; D008774:Methylphenidate / Q000008:administration & dosage* / Q000097:blood / Q000493:pharmacokinetics*; D008875:Middle Aged; D013997:Time Factors
D002214:Capsules; D003692:Delayed-Action Preparations; D004041:Dietary Fats; D008774:Methylphenidate