Pharmacokinetics of anti tumor necrosis factor antibody (infliximab) in children with acute GVHD involving the gastrointestinal tract
Notice bibliographique
Résumé
Infliximab (REMICADE®, Centocor), a chimeric anti-TNFα monoclonal antibody, has been used in the management of patients with steroid-refractory acute GVHD. Though preliminary results using infliximab have been encouraging, the pharmacokinetics (Pk) of infliximab in this clinical setting have yet to be defined. A prospective trial examining the Pk of infliximab in pediatric patients with gastrointestinal (GI) GVHD was undertaken. Five subjects (median 11 yrs, range 9 mo–17 yrs) with GI GVHD were enrolled. All subjects had histologic confirmation of GVHD and had failed > 48 hours of corticosteroids prior to study entry. Subjects received a single 5 mg/kg dose of infliximab. PK and pharmacodynamic samples were drawn at 16 time points (hours 0, 1, 2, 6, 24, 48, 96, weekly days 7–42, days 56, 70, 84). Based upon existing Pk data in patients with Crohn’s disease, the time required to reach a trough concentration ≤2 mcg/ml was the defined primary study endpoint. Results: Dosing was well tolerated in all five subjects. Infliximab concentrations are as follows: Peak concentrations (Cmax) ranged from 64-160 mcg/ml and were achieved by hours 2–6. Drug concentrations > 20 mcg/ml were maintained for > 7 days in all subjects. The primary endpoint (trough concentration □ 2 mcg/ml) was reached on days 28, 35, 21, 35, and 7(asterisk) (median 28 days, mean 25 days), respectively. Infectious complications with a possible attribution to infliximab included endocarditis on day 21 in 1 subject and CMV reactivation 1 month post infliximab in a second subject. No invasive fungal infections were seen. Durable complete responses of GVHD were seen in 2 subjects by days 7 and 28, respectively. Two subjects are alive (6 months and 16 months). Conclusion: In summary, pharmacokinetics of infliximab indicate that concentrations > the targeted threshold level can be maintained for several weeks following a single 5 mg/kg dose in patients with GI GVHD. A phase II clinical trial, with dosing intervals based upon these Pk parameters, will be required. This investigator-initiated study was conducted through the Pediatric Blood and Marrow Transplant Consortium. Infliximab and partial financial support were provided by Centocor, Inc. Infliximab (REMICADE®, Centocor), a chimeric anti-TNFα monoclonal antibody, has been used in the management of patients with steroid-refractory acute GVHD. Though preliminary results using infliximab have been encouraging, the pharmacokinetics (Pk) of infliximab in this clinical setting have yet to be defined. A prospective trial examining the Pk of infliximab in pediatric patients with gastrointestinal (GI) GVHD was undertaken. Five subjects (median 11 yrs, range 9 mo–17 yrs) with GI GVHD were enrolled. All subjects had histologic confirmation of GVHD and had failed > 48 hours of corticosteroids prior to study entry. Subjects received a single 5 mg/kg dose of infliximab. PK and pharmacodynamic samples were drawn at 16 time points (hours 0, 1, 2, 6, 24, 48, 96, weekly days 7–42, days 56, 70, 84). Based upon existing Pk data in patients with Crohn’s disease, the time required to reach a trough concentration ≤2 mcg/ml was the defined primary study endpoint. Results: Dosing was well tolerated in all five subjects. Infliximab concentrations are as follows: Peak concentrations (Cmax) ranged from 64-160 mcg/ml and were achieved by hours 2–6. Drug concentrations > 20 mcg/ml were maintained for > 7 days in all subjects. The primary endpoint (trough concentration □ 2 mcg/ml) was reached on days 28, 35, 21, 35, and 7(asterisk) (median 28 days, mean 25 days), respectively. Infectious complications with a possible attribution to infliximab included endocarditis on day 21 in 1 subject and CMV reactivation 1 month post infliximab in a second subject. No invasive fungal infections were seen. Durable complete responses of GVHD were seen in 2 subjects by days 7 and 28, respectively. Two subjects are alive (6 months and 16 months). Conclusion: In summary, pharmacokinetics of infliximab indicate that concentrations > the targeted threshold level can be maintained for several weeks following a single 5 mg/kg dose in patients with GI GVHD. A phase II clinical trial, with dosing intervals based upon these Pk parameters, will be required. This investigator-initiated study was conducted through the Pediatric Blood and Marrow Transplant Consortium. Infliximab and partial financial support were provided by Centocor, Inc.
Récupéré en direct depuis OpenAlex et désinversé. Les résumés ne sont pas conservés dans cette base de données : les index inversés représentent 8,6 Go des 9,3 Go de texte de la base, et le serveur dispose de 13 Go libres.
Comment cette classification a été obtenuedéplier
Prédiction distillée sur la base complète
Imitation des enseignantsNi prévalence calibrée, ni vérité terrain. Validation humaine à venir. Apprise à partir de 10 348 étiquettes directes de Codex et de 10 348 étiquettes directes de Gemma. Le mode candidate est l'union des têtes enseignantes seuillées; le consensus est leur intersection. Ces sorties portent le statut machine_predicted_unvalidated et ne sont ni des étiquettes humaines ni des étiquettes directes de modèles de pointe.
Scores Codex et Gemma par catégorie
| Catégorie | Codex | Gemma |
|---|---|---|
| Métarecherche | 0,000 | 0,000 |
| Méta-épidémiologie (sens strict) | 0,000 | 0,000 |
| Méta-épidémiologie (sens large) | 0,000 | 0,000 |
| Bibliométrie | 0,000 | 0,000 |
| Études des sciences et des technologies | 0,000 | 0,000 |
| Communication savante | 0,000 | 0,000 |
| Science ouverte | 0,000 | 0,000 |
| Intégrité de la recherche | 0,000 | 0,000 |
| Charge utile insuffisante (le modèle a refusé de juger) | 0,000 | 0,000 |
Scores machine (provisoires)
Les deux têtes enseignantes du modèle étudiant, lues sur ce travail. Un score ordonne la base pour la relecture; il n'affirme jamais une catégorie, et le statut de validation accompagne chaque rangée tel quel.
Scores de référence d'un modèle non mature (critères de maturité non atteints, 7 itérations). Un score ordonne; il n'affirme jamais une catégorie.
score_only:v0-immature-baseline · tel quel depuis la passe de notation : score_only signifie que le nombre peut ordonner les travaux, et qu'aucune étiquette de catégorie n'en découleClassification
machine, non validéePrédiction automatique; un appel candidat d’une seule tête enseignante, pas un consensus.
Le détail, modèle par modèle et score par score, se trouve en fin de page sous « Comment cette classification a été obtenue ».