PHARMACOKINETICS OF METHYLPHENIDATE FOLLOWING TWO ORAL FORMULATIONS (IMMEDIATE AND SUSTAINED RELEASE) IN THE DOG

摘要

Methylphenidate (MPH) is an immediate-release (IR) or sustained-release (SR)drug used to treat attention-deficit hyperactivity disorder. Eight dogs were randomlyassigned 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 orSR tablet. After blood collections at specific times, the concentrations of d,l-MPH inplasma were evaluated by high-performance liquid chromatography. Following both IR andSR oral administration of d,l-MPH, the animals did not show any side effects, except thatmild 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 acharacteristic, one-compartment drug model. The relative bioavailability of the SRformulation was 30.58±13.73%. Significant differences between the two administrationswere found in Tmax, Cmax, AUC, and Cl. Despite low drug concentrations in the blood, theSR formulation ensured uniformity of d,l-MPH plasma concentrations and, thus, a simplerand easier titration. In conclusion, the tested dosage appears to be too low for clinicalapplication in canines, and an increase in dosing is suggested. Further pharmacodynamicsstudies are necessary to support this speculation