Population pharmacokinetics of tofacitinib in patients with psoriatic arthritisâ©.
Int J Clin Pharmacol Ther
; 57(9): 464-473, 2019 Sep.
Article
en En
| MEDLINE
| ID: mdl-31319908
ABSTRACT
OBJECTIVE:
Tofacitinib is an oral Janus kinase inhibitor for the treatment of psoriatic arthritis (PsA). This analysis characterized the pharmacokinetics (PK) of tofacitinib in adult patients with active PsA and evaluated the impact of covariates (baseline characteristics) on the disposition of tofacitinib. MATERIALS ANDMETHODS:
Data were pooled from two phase 3 studies of tofacitinib of up to 12 months' duration in patients with active PsA (OPAL Broaden (NCT01877668); OPAL Beyond (NCT01882439)). This analysis included 650 tofacitinib-treated patients with 3,252 tofacitinib plasma concentration measurements. Tofacitinib PK was described using a one-compartment disposition model parameterized in terms of apparent oral clearance (CL/F) and apparent volume of distribution (V/F) with first-order absorption rate (Ka) and a lag time. Covariates evaluated were baseline age, baseline body weight, sex, race, ethnicity, baseline creatinine clearance (BCCL), and baseline C-reactive protein.RESULTS:
The estimates (95% confidence interval) of PK model parameters of a reference patient were CL/F 20.4 (18.6, 21.8) L/h; V/F 110 (108, 113) L; and Ka 13.8 (12.1, 16.6)/h. Among the covariates, only BCCL led to clinically relevant changes in exposure; however, this was consistent with the known contribution of renal excretion to the total clearance of tofacitinib (~ 30%).CONCLUSION:
Tofacitinib did not require dose modification or restrictions for age, body weight, sex, race, ethnicity, or baseline disease severity in patients with active PsA based on the magnitude of exposure relative to a reference patient. Dosing adjustments for renal impairment were derived from a separate phase 1 study.
Texto completo:
1
Bases de datos:
MEDLINE
Asunto principal:
Piperidinas
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Pirimidinas
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Pirroles
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Artritis Psoriásica
Tipo de estudio:
Clinical_trials
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Prognostic_studies
Límite:
Adolescent
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Adult
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Aged
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Female
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Humans
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Male
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Middle aged
Idioma:
En
Revista:
Int J Clin Pharmacol Ther
Asunto de la revista:
FARMACOLOGIA
/
TERAPIA POR MEDICAMENTOS
Año:
2019
Tipo del documento:
Article