Pharmacokinetics of methylphenidate after oral administration of immediate and sustained-release preparations in Beagle dogs.
Methylphenidate (MPH) is a drug administered either as an immediate- or sustained-release preparation for the treatment of attention deficit hyperactivity disorder in humans. The aim of this study was to determine the pharmacokinetics of two different MPH formulations in the dog. Eight dogs were randomly assigned to two treatment groups using a two-part randomised, cross-over experimental design. Each subject received a single dose of 20 mg d,l-MPH as an immediate- (IR) or sustained-release (SR) tablet. Blood was collected at specific times, and the plasma concentrations of d,l-MPH were evaluated using high performance liquid chromatography. There were no adverse effects following the oral administration of d,l-MPH in either the IR or SR groups, apart from mild hyperkinesia which was observed in some of the IR group. The plasma concentration data of d,l-MPH were best described by a one-compartment model. There were significant differences in the maximum concentration (C(max)), time to C(max) (T(max)), area under the curve (AUC) and clearance (Cl) between the two formulations. The relative bioavailability of the SR formulation was 30.58±13.73% and, despite low drug plasma concentrations, the SR formulation resulted in uniform plasma concentrations of d,l-MPH. However, the dose rate of the SR formulation used in this study resulted in plasma concentrations that were below effective levels for clinical efficacy, so further studies are required to confirm the suitability of higher dose rates for clinical use.
Lavy
E
E
School of Veterinary Medicine, Hebrew University of Jerusalem, PO Box 12, Rehovot 76100, Israel.
Prise
U
U
Soldani
G
G
Neri
D
D
Brandriss
N
N
Bar Chaim
A
A
Giorgi
M
M
D000284:Administration, Oral; D000704:Analysis of Variance; D000818:Animals; D019540:Area Under Curve; D000697:Central Nervous System Stimulants / Q000008:administration & dosage* / Q000097:blood / Q000493:pharmacokinetics*; D002851:Chromatography, High Pressure Liquid / Q000662:veterinary; D018592:Cross-Over Studies; D003692:Delayed-Action Preparations / Q000493:pharmacokinetics; D004285:Dogs; D005260:Female; D006801:Humans; D008297:Male; D008774:Methylphenidate / Q000008:administration & dosage* / Q000097:blood / Q000493:pharmacokinetics*; D010375:Pedigree; D011897:Random Allocation
D000697:Central Nervous System Stimulants; D003692:Delayed-Action Preparations; D008774:Methylphenidate