The Pharmacokinetics of Etanercept in Healthy Volunteers
Abstract
Abstract
OBJECTIVE:
To describe the pharmacokinetics of etanercept when administered by subcutaneous injection in single doses to healthy volunteers.
METHODS:
Twenty-six healthy volunteers between 19 and 50 years of age received single doses of etanercept 25 mg by subcutaneous injection into the abdomen. Serial serum samples were collected for 21 days. An enzyme-linked immunosorbent assay with a quantitation limit of 0.3 ng/mL was used to measure the drug concentrations.
RESULTS:
Etanercept was well tolerated by healthy volunteers. A one-compartment model was found to best describe the concentration–time data and was used to determine the pharmacokinetic parameters. Etanercept is slowly absorbed from the site of injection with a time of peak concentration (± SD) of 51 ± 14 hours; peak concentration was 1.46 ± 0.72 mg/L. The AUC was 235 ± 98 mg•h/L, apparent clearance was 132 ± 85 mL/h, apparent volume of distribution was 12 ± 6 L, and the half-life was 68 ± 19 hours.
CONCLUSIONS:
Etanercept was slowly absorbed and slowly eliminated after subcutaneous administration. Dosing at the recommended rate of 25 mg twice weekly would be expected to result in concentrations of approximately 3 mg/L. Intersubject variability for apparent clearance in healthy volunteers was 64%.
Resumen
OBJETIVO:
Describir la farmacocinética de etanercept cuando se administra en dosis sencilla por inyección subcutánea a voluntarios saludables.
MÉTODOS:
Veintiseis voluntarios saludables entre las edades et 19 a 50 años recibieron etanercept en dosis sencilla de 25 mg por inyección subcutánea. Muestras séricas en serie fueron recolectadas por 21 días. Para medir la concentración del fármaco, se utilizó un inmunoensayo de enzima ligada (ELISA, por sus siglas en inglés) con límite de cuantización de 0.3 ng/mL.
RESULTADOS:
Etanercept fue bien tolerado por los voluntarios saludables. Se encontró que un modelo de un compartimiento es el que mejor describe los datos de concentración contra tiempo y se usó para determinar los parámetros farmacocinéticos. Etanercept se absorbe lentamente del sitio de inyección con un tiempo de concentración pico (± desviación estándar) de 51 ± 14 horas y una concentración pico de 1.46 ± 0.72 mg/L. El área bajo la curva de concentración contra tiempo fue de 235 ± 98 mg•h/L, la depuración aparente fue de 132 ± 85 mL/h, el volumen de distribución aparente fue de 12 ± 6 L, y la vida media de 68 ± 19 horas.
CONCLUSIONES:
Se observó que etanercept se absorbe y se elimina lentamente después de administración subcutánea. Dosificar a la razón recomendada de 25 mg dos veces a la semana debe resultar en una concentración aproximada de 3 mg/L. La variabilidad entre sujetos para la depuración aparente fue de 64%.
Résumé
OBJECTIF:
Décrire la pharmacocinétique de l'etanercept lorsqu'administré par voie sous-cutanée en dos unique à des volontaires sains.
MÉTHODOLOGIE:
Vingt-six volontaires sains âgés de 19 à 50 ans ont reçu une dose unique de 25 mg d'etanercept par voie sous-cutanée administrée à la région abdominale. Des échantillons sanguins ont ensuite été collectés pendant 21 jours. Les concentrations sériques d'etanercept ont été mesurées par un essai immuno-enzymatique pour lequel la limite de détection était de 0.3 ng/mL.
RÉSULTATS:
Les volontaires sains ont bien toléré l'etanercept. C'est un modèle unicompartimental qui décrit le mieux la relation entre les concentrations sériques et le temps. L'etanercept est lentement absorbé à partir du site d'injection avec un tmax de 51 ± 14 heures et une Cmax de 1.46 ± 0.72 mg/L. La clairance apparente est de 132 ± 85 mL/h, alors que le volume de distribution apparent atteint 12 ± 6 L, et la demi-vie de 68 ± 19 heures.
CONCLUSIONS:
L'etanercept est absorbé et éliminé lentement suite à une administration par voie sous-cutanée. La dose recommandée, i.e., 25 mg 2 fois par semaine, devrait produire des concentrations d'environ 3 mg/L. La variation de la clairance entre les sujets s'éleve à 64% chez les volontaires sains.
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Article first published: February 2000
Issue published: February 2000
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Published online: February 1, 2000
Issue published: February 2000
PubMed: 10676822
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