Population pharmacokinetic analysis of mycophenolic acid coadministered with either tasocitinib (CP-690,550) or tacrolimus in adult renal allograft recipients.
Ther Drug Monit
; 32(6): 778-81, 2010 Dec.
Article
em En
| MEDLINE
| ID: mdl-20926996
ABSTRACT
Tasocitinib (CP-690,550) is an orally active Janus kinase inhibitor that is in development for prophylaxis of acute rejection after kidney transplantation and for the treatment of select autoimmune diseases. The current study was conducted to evaluate the systemic exposure of mycophenolic acid (MPA) in de novo kidney transplant patients when coadministered with tasocitinib compared with exposure in patients receiving tacrolimus, which has no effect on MPA pharmacokinetics. Plasma MPA concentrations were obtained from 17 adult patients who received either 15 mg or 30 mg tasocitinib twice daily (eight patients) or tacrolimus (nine patients) after kidney transplantation. All patients also received concomitant mycophenolate mofetil, prednisone, and basiliximab induction. The median mycophenolate mofetil dose was 1000 mg twice daily. A two-compartment population pharmacokinetic model estimating oral clearance, between-patient variability in oral clearance, central volume of distribution, and residual variability in combination with historical estimates of first-order absorption rate constant, intercompartmental clearance, and peripheral volume of distribution adequately described the sparse MPA data. Based on individual estimates oral clearance from the population pharmacokinetic model, mean steady-state area under the concentration-time curve values for a mycophenolate mofetil dose of 1000 mg twice daily were 63 mg·hr/L (22%) and 59 mg·hr/L (36%) for the tasocitinib and tacrolimus groups, respectively. These results indicate that tasocitinib does not influence systemic MPA exposure.
Texto completo:
1
Base de dados:
MEDLINE
Assunto principal:
Pirimidinas
/
Pirróis
/
Transplante de Rim
/
Tacrolimo
/
Imunossupressores
/
Ácido Micofenólico
Tipo de estudo:
Clinical_trials
/
Prognostic_studies
Limite:
Adult
/
Humans
Idioma:
En
Ano de publicação:
2010
Tipo de documento:
Article