Tofacitinib pharmacokinetics in children and adolescents with juvenile idiopathic arthritis.
CPT Pharmacometrics Syst Pharmacol
; 13(4): 599-611, 2024 04.
Article
in En
| MEDLINE
| ID: mdl-38298058
ABSTRACT
These analyses characterized tofacitinib pharmacokinetics (PKs) in children and adolescents with juvenile idiopathic arthritis (JIA). Data were pooled from phase I (NCT01513902), phase III (NCT02592434), and open-label, long-term extension (NCT01500551) studies of tofacitinib tablet/solution (weight-based doses administered twice daily [b.i.d.]) in patients with JIA aged 2 to less than 18 years. Population PK modeling used a nonlinear mixed-effects approach, with covariates identified using stepwise forward-inclusion backward-deletion procedures. Simulations were performed to derive dosing recommendations for children and adolescents with JIA. Two hundred forty-six pediatric patients were included in the population PK model. A one-compartment model with first-order elimination and absorption with body weight as a covariate for oral clearance and apparent volume of distribution sufficiently described the data. Oral solution was associated with comparable average concentration (Cavg) and slightly higher (113.9%) maximum concentration (Cmax) versus tablet, which was confirmed by a subsequent randomized, open-label, bioavailability study conducted in healthy adult participants (n = 12) by demonstrating adjusted geometric mean ratios (90% confidence interval) between oral solution and tablet of 1.04 (1.00-1.09) and 1.10 (1.00-1.21) for area under the curve extrapolated to infinity and Cmax, respectively (NCT04111614). A dosing regimen of 3.2 mg b.i.d. solution in patients 10 to less than 20 kg, 4 mg b.i.d. solution in patients 20 to less than 40 kg, and 5 mg b.i.d. tablet/solution in patients greater than or equal to 40 kg, irrespective of age, was proposed to achieve constant Cavg across weight groups. In summary, population PK characterization informed a simplified tofacitinib dosing regimen that has been implemented in pediatric patients with JIA.
Full text:
1
Collection:
01-internacional
Database:
MEDLINE
Main subject:
Arthritis, Juvenile
Type of study:
Clinical_trials
/
Prognostic_studies
Limits:
Adolescent
/
Adult
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Child
/
Humans
Language:
En
Journal:
CPT Pharmacometrics Syst Pharmacol
/
CPT: pharmacomet. syst. pharmacol
/
CPT: pharmacometrics & systems pharmacology
Year:
2024
Document type:
Article
Affiliation country:
Country of publication: