Pharmacokinetics of methylphenidate after oral administration of immediate and sustained-release preparations in Beagle dogs     

E. Lavy  U. Prise  G. Soldani  D. Neri  N. Brandriss  A. Bar Chaim  M. Giorgi 《Veterinary journal (London, England : 1997)》2011,189(3):336-340

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.  相似文献   

Pharmacokinetics of methylphenidate following two oral formulations (immediate and sustained release) in the dog     

Giorgi  M.  Prise  U.  Soldani  G.  Neri  D.  Lavy  E. 《Veterinary research communications》2010,34(1):73-77

Methylphenidate (MPH) is an immediate-release (IR) or sustained-release (SR) drug used to treat attention-deficit hyperactivity disorder. Eight dogs were randomly assigned to two treatment groups, using an open, single-dose, two-treatment, two-period, randomized, crossover design. Each subject received a single dose of 20 mg d,l-MPH IR or SR tablet. After blood collections at specific times, the concentrations of d,l-MPH in plasma were evaluated by high-performance liquid chromatography. Following both IR and SR oral administration of d,l-MPH, the animals did not show any side effects, except that mild hyperkinesia was observed in a few subjects belonging to the IR treatment group. After both administrations, the concentration data for d,l-MPH in plasma displayed a characteristic, one-compartment drug model. The relative bioavailability of the SR formulation was 30.58 ± 13.73%. Significant differences between the two administrations were found in T_max, C_max, AUC, and Cl. Despite low drug concentrations in the blood, the SR formulation ensured uniformity of d,l-MPH plasma concentrations and, thus, a simpler and easier titration. In conclusion, the tested dosage appears to be too low for clinical application in canines, and an increase in dosing is suggested. Further pharmacodynamics studies are necessary to support this speculation.

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