Population Pharmacokinetic Modeling of Gemtuzumab Ozogamicin in Adult Patients with Acute Myeloid Leukemia.
Adolescent
Adult
Aged
Aged, 80 and over
Antibodies, Monoclonal
Antineoplastic Agents, Immunological
/ administration & dosage
Calicheamicins
/ blood
Drug Design
Female
Gemtuzumab
/ administration & dosage
Humans
Leukemia, Myeloid, Acute
/ blood
Male
Middle Aged
Sialic Acid Binding Ig-like Lectin 3
/ antagonists & inhibitors
United States
United States Food and Drug Administration
Young Adult
Journal
Clinical pharmacokinetics
ISSN: 1179-1926
Titre abrégé: Clin Pharmacokinet
Pays: Switzerland
ID NLM: 7606849
Informations de publication
Date de publication:
03 2019
03 2019
Historique:
pubmed:
1
8
2018
medline:
23
5
2020
entrez:
1
8
2018
Statut:
ppublish
Résumé
Gemtuzumab ozogamicin is an antibody-drug conjugate composed of the anti-CD33 monoclonal antibody hP67.6 covalently linked to N-acetyl-gamma-calicheamicin dimethylhydrazide, a potent cytotoxic antibiotic. The aim of this study was to characterize the population pharmacokinetics of gemtuzumab ozogamicin, represented by total hP67.6 antibody and unconjugated calicheamicin, in adult patients with acute myeloid leukemia to support drug dosing strategies and explore intrinsic and extrinsic factors that may influence exposure. Pharmacokinetic data from seven previous phase I and II studies in adult patients with relapsed, refractory, or de novo acute myeloid leukemia were integrated and analyzed using nonlinear mixed-effects modeling. The pharmacokinetics of total hP67.6 antibody was described in 407 patients (5643 concentrations) who received gemtuzumab ozogamicin doses ranging from 0.25 to 9 mg/m Total hP67.6 antibody disposition did not appear altered in patients with mild or moderate renal disease or hepatic impairment. Gemtuzumab ozogamicin was approved for the treatment of acute myeloid leukemia by the US Food and Drug Administration in September 2017. The model-based simulations described here provided a pharmacokinetic rationale for the approved dosing regimen of 3 mg/m
Sections du résumé
BACKGROUND AND OBJECTIVE
Gemtuzumab ozogamicin is an antibody-drug conjugate composed of the anti-CD33 monoclonal antibody hP67.6 covalently linked to N-acetyl-gamma-calicheamicin dimethylhydrazide, a potent cytotoxic antibiotic. The aim of this study was to characterize the population pharmacokinetics of gemtuzumab ozogamicin, represented by total hP67.6 antibody and unconjugated calicheamicin, in adult patients with acute myeloid leukemia to support drug dosing strategies and explore intrinsic and extrinsic factors that may influence exposure. Pharmacokinetic data from seven previous phase I and II studies in adult patients with relapsed, refractory, or de novo acute myeloid leukemia were integrated and analyzed using nonlinear mixed-effects modeling.
METHODS
The pharmacokinetics of total hP67.6 antibody was described in 407 patients (5643 concentrations) who received gemtuzumab ozogamicin doses ranging from 0.25 to 9 mg/m
RESULTS AND CONCLUSION
Total hP67.6 antibody disposition did not appear altered in patients with mild or moderate renal disease or hepatic impairment. Gemtuzumab ozogamicin was approved for the treatment of acute myeloid leukemia by the US Food and Drug Administration in September 2017. The model-based simulations described here provided a pharmacokinetic rationale for the approved dosing regimen of 3 mg/m
Identifiants
pubmed: 30062662
doi: 10.1007/s40262-018-0699-5
pii: 10.1007/s40262-018-0699-5
doi:
Substances chimiques
Antibodies, Monoclonal
0
Antineoplastic Agents, Immunological
0
CD33 protein, human
0
Calicheamicins
0
Sialic Acid Binding Ig-like Lectin 3
0
Gemtuzumab
93NS566KF7
Banques de données
ClinicalTrials.gov
['NCT00003131', 'NCT00003673', 'NCT00037596', 'NCT00037583']
Types de publication
Clinical Trial, Phase I
Clinical Trial, Phase II
Journal Article
Research Support, Non-U.S. Gov't
Langues
eng
Sous-ensembles de citation
IM
Pagination
335-347Références
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