Pharmacokinetic Study of Conversion Between 2 Formulations of Once-daily Extended-release Tacrolimus in Stable Lung Transplant Patients.
Transplantation
; 102(10): e439-e446, 2018 10.
Article
en En
| MEDLINE
| ID: mdl-29965950
ABSTRACT
BACKGROUND:
The aim of this study was to compare the pharmacokinetic profile, tolerability, and safety of a novel once-daily extended-release formulation of tacrolimus (LCPT) with that of once-daily prolonged-release tacrolimus (ODT) in stable adult lung transplant (LT) recipients.METHODS:
Phase II, open-label, single-arm, single-center, prospective pilot pharmacokinetic study. Study population comprised 20 stable LT recipients receiving ODT, mean age 55.9 years (range, 38-67 years), 13 (65%) men. Patients were switched to LCPT in a 10.7 (mg/mg) conversion dose. Follow-up was 6 months, and cystic fibrosis patients were excluded. Two 24-hour pharmacokinetic profiles were obtained for each patient, the first on day -14 and the second on day +14 after switching to LCPT. Pharmacokinetic parameters and safety were compared.RESULTS:
Mean (SD) area under the concentration-time curve from 0 to 24 hours was 253.97 (61.90) ng/mL per hour for ODT and 282.44 (68.2) ng/mL per hour for LCPT. Systemic exposure was similar in both (Schuirmann two 1-sided test). Mean (SD) dose was 5.05 (1.67) mg in ODT and 3.36 (1.03) mg in LCPT (P = 0.0002). Time to maximum concentration was 125 minutes for ODT and 325 minutes for LCPT (P < 0.001). Correlation between area under the concentration-time curve from 0 to 24 hours and C24 was 0.896 (r) for ODT and 0.893 (r) for LCPT. There were no differences in adverse effects. At 6 months, conversion dose was 10.59 (mg/mg) in patients with unchanged minimum plasma concentration target levels.CONCLUSIONS:
Switching from ODT to LCPT was safe and well tolerated in stable LT recipients without cystic fibrosis. A significantly lower dose of LCPT allows similar bioavailability. A conversion ratio 10.6 could be enough to maintain similar target levels.
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Base de datos:
MEDLINE
Asunto principal:
Terapia de Inmunosupresión
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Trasplante de Pulmón
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Tacrolimus
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Rechazo de Injerto
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Inmunosupresores
Tipo de estudio:
Observational_studies
/
Prognostic_studies
Idioma:
En
Revista:
Transplantation
Año:
2018
Tipo del documento:
Article