Post by Amtram on Mar 1, 2014 13:05:46 GMT -5
From drugs.com:
Pharmacodynamics
Methylphenidate is a racemic mixture comprised of the d- and l-isomers. The d-isomer is more pharmacologically active than the l-isomer. Methylphenidate is thought to block the reuptake of norepinephrine and dopamine into the presynaptic neuron and increase the release of these monoamines into the extraneuronal space.
Pharmacokinetics
Absorption
Following a single, 60 mg oral dose of Quillivant XR in 28 healthy adult subjects in a crossover study under fasting conditions, d-methylphenidate (d-MPH) mean (± SD) peak plasma concentrations of 13.6 (± 5.8) ng/mL occurred at a median time of 5.0 hours after dosing (Figure 2). The relative bioavailability of Quillivant XR compared to Methylphenidate IR oral solution (2×30 mg, q6h) is 95%.
Figure 2. Mean d-Methylphenidate Plasma Concentration-Time Profiles
The single dose pharmacokinetics of d-MPH under fed conditions are summarized (Table 3) from studies in children and adolescents with ADHD, and healthy adults following an oral dose of 60 mg Quillivant XR.
Table 3. d-MPH PK Parameters (mean ±SD) after 60 mg oral dosing of Quillivant XR* PK Parameter Children† (n=3) Adolescent† (n=4) Adult (n=27)
*
Breakfast was given 30 min prior to drug administration
†
total MPH measured in children (9–12 years old) and adolescents (13–15 years old), l-MPH <2% of d-MPH in circulation
‡
data presented as median (range)
Tmax (hr)‡ 4.05 (3.98–6.0) 2.0 (1.98–4.0) 4.0 (1.3–7.3)
T1/2 (hr) 5.2±0.1 5.0±0.2 5.2±1.0
Cmax (ng/mL) 34.4±14.0 21.1±5.9 17.0±7.7
AUCinf (hr*ng/mL) 378±175 178±54.2 163.2±80.3
Cl (L/hr/kg) 4.27±0.70 5.06±1.42 5.66±2.15
Metabolism and Excretion
Following a single 60 mg oral dose of Quillivant XR in 28 healthy adult subjects under fasting conditions, the mean plasma terminal elimination half-life of d-methylphenidate was 5.6 (± 0.8) hours.
In humans, methylphenidate is metabolized primarily via deesterification to alpha-phenyl-piperidine acetic acid (PPAA). The metabolite has little or no pharmacologic activity.
After oral dosing of radiolabeled methylphenidate in humans, about 90% of the radioactivity was recovered in urine. The main urinary metabolite was PPAA, accounting for approximately 80% of the dose.
Food Effects
In a study in adult volunteers to investigate the effects of a high-fat meal on the bioavailability of Quillivant XR at a dose of 60 mg, the presence of food reduced the time to peak concentration by approximately 1 hour (fed: 4 hours vs. fasted: 5 hours). Overall, a high-fat meal increased the average Cmax of Quillivant XR by about 28% and the AUC by about 19%. These changes are not considered clinically significant.
Methylphenidate is a racemic mixture comprised of the d- and l-isomers. The d-isomer is more pharmacologically active than the l-isomer. Methylphenidate is thought to block the reuptake of norepinephrine and dopamine into the presynaptic neuron and increase the release of these monoamines into the extraneuronal space.
Pharmacokinetics
Absorption
Following a single, 60 mg oral dose of Quillivant XR in 28 healthy adult subjects in a crossover study under fasting conditions, d-methylphenidate (d-MPH) mean (± SD) peak plasma concentrations of 13.6 (± 5.8) ng/mL occurred at a median time of 5.0 hours after dosing (Figure 2). The relative bioavailability of Quillivant XR compared to Methylphenidate IR oral solution (2×30 mg, q6h) is 95%.
Figure 2. Mean d-Methylphenidate Plasma Concentration-Time Profiles
The single dose pharmacokinetics of d-MPH under fed conditions are summarized (Table 3) from studies in children and adolescents with ADHD, and healthy adults following an oral dose of 60 mg Quillivant XR.
Table 3. d-MPH PK Parameters (mean ±SD) after 60 mg oral dosing of Quillivant XR* PK Parameter Children† (n=3) Adolescent† (n=4) Adult (n=27)
*
Breakfast was given 30 min prior to drug administration
†
total MPH measured in children (9–12 years old) and adolescents (13–15 years old), l-MPH <2% of d-MPH in circulation
‡
data presented as median (range)
Tmax (hr)‡ 4.05 (3.98–6.0) 2.0 (1.98–4.0) 4.0 (1.3–7.3)
T1/2 (hr) 5.2±0.1 5.0±0.2 5.2±1.0
Cmax (ng/mL) 34.4±14.0 21.1±5.9 17.0±7.7
AUCinf (hr*ng/mL) 378±175 178±54.2 163.2±80.3
Cl (L/hr/kg) 4.27±0.70 5.06±1.42 5.66±2.15
Metabolism and Excretion
Following a single 60 mg oral dose of Quillivant XR in 28 healthy adult subjects under fasting conditions, the mean plasma terminal elimination half-life of d-methylphenidate was 5.6 (± 0.8) hours.
In humans, methylphenidate is metabolized primarily via deesterification to alpha-phenyl-piperidine acetic acid (PPAA). The metabolite has little or no pharmacologic activity.
After oral dosing of radiolabeled methylphenidate in humans, about 90% of the radioactivity was recovered in urine. The main urinary metabolite was PPAA, accounting for approximately 80% of the dose.
Food Effects
In a study in adult volunteers to investigate the effects of a high-fat meal on the bioavailability of Quillivant XR at a dose of 60 mg, the presence of food reduced the time to peak concentration by approximately 1 hour (fed: 4 hours vs. fasted: 5 hours). Overall, a high-fat meal increased the average Cmax of Quillivant XR by about 28% and the AUC by about 19%. These changes are not considered clinically significant.