Methylphenidate

Absorption

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 hours after dosing (Figure 2). The relative bioavailability of QUILLIVANT XR compared to Methylphenidate IR oral solution (2x30 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)
T
max
(hr)
‡
4.05 (3.98-6.0)
2.0 (1.98-4.0)
4.0 (1.3-7.3)
T
1/2
(hr)
5.2±0.1
5.0±0.2
5.2±1.0
C
max (ng/mL)
34.4±14.0
21.1±5.9
17.0±7.7
AUC
inf (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
* Breakfast was given 30 min prior to drug administration† total MPH measured in children (9 to 12 years old) and adolescents (13 to 15 years old), l-MPH <2% of d-MPH in circulation‡ data presented as median (range)
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.
Elimination
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.
Metabolism
In humans, methylphenidate is metabolized primarily via deesterification to alpha-phenyl-piperidine acetic acid (PPAA). The metabolite has little or no pharmacologic activity.
Excretion
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.
Alcohol Effect
An in vitro study was conducted to explore the effect of alcohol on the release characteristics of methylphenidate from QUILLIVANT XR Oral Suspension. At alcohol concentrations of 5% and 10%, there was no effect of alcohol on the release characteristics of methylphenidate. At 20% alcohol concentration, there was on average a 20% increase in drug exposure [see
Dosage and Administration (
2.2
)
].
Specific Populations
Sex
There is insufficient experience with the use of QUILLIVANT XR to detect gender variations in pharmacokinetics.
Race
There is insufficient experience with the use of QUILLIVANT XR to detect ethnic variations in pharmacokinetics.
Age
The pharmacokinetics of methylphenidate after QUILLIVANT XR administration were studied in pediatric patients with ADHD between 9 and 15 years of age. After a single oral dose of 60 mg QUILLIVANT XR, plasma concentrations of methylphenidate in children (9 to 12 years old; n=3) were approximately twice the concentrations observed in adults. The plasma concentrations in adolescent patients (13 to 15 years old; n=4) were similar to those in adults.
Renal Impairment
There is no experience with the use of QUILLIVANT XR in patients with renal insufficiency. After oral administration of radiolabeled methylphenidate in humans, methylphenidate was extensively metabolized and approximately 80% of the radioactivity was excreted in the urine in the form of PPAA. Since renal clearance is not an important route of methylphenidate clearance, renal insufficiency is expected to have little effect on the pharmacokinetics of QUILLIVANT XR.
Hepatic Impairment
There is no …