ArticleCancer chemotherapy and pharmacology2010
Pharmacokinetics of orally administered ABT-751 in children with neuroblastoma and other solid tumors.
Article in Cancer chemotherapy and pharmacology, 2010. The graph could read no effect estimate from its abstract, so it casts no vote on the map. It is linked to trial NCT00036959 (Phase I Trial and Pharmacokinetic Study of ABT-751, an Orally Bioavailable Tubulin Binding Agent, on a 7 Day and 21 Day Dosing Schedule in Pediatric Patients With Refractory Solid Tumors), which is not on this map. Cited by 5 papers.
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The trial behind it
Trials whose registry record cites this paper, or whose number appears in the abstract. A trial that started after this paper was published is citing it as background, not reporting it.
Phase I Trial and Pharmacokinetic Study of ABT-751, an Orally Bioavailable Tubulin Binding Agent, on a 7 Day and 21 Day Dosing Schedule in Pediatric Patients With Refractory Solid Tumors
Who cites it
5 citing papers in PubMed, 18 citations in OpenAlex.
- Time to disease progression in children with relapsed or refractory neuroblastoma treated with ABT-751: a report from the Children's Oncology Group (ANBL0621).Pediatric blood & cancer · 2014Trial
- Microtubule-Targeting Agents: Advances in Tubulin Binding and Small Molecule Therapy for Gliomas and Neurodegenerative Diseases.International journal of molecular sciences · 2025Review
- Phase 1 Study of ABT-751 in Combination With CAPIRI (Capecitabine and Irinotecan) and Bevacizumab in Patients With Advanced Colorectal Cancer.Journal of clinical pharmacology · 2016Article
- Preclinical discovery of candidate genes to guide pharmacogenetics during phase I development: the example of the novel anticancer agent ABT-751.Pharmacogenetics and genomics · 2013Article
- Orally bioavailable tubulin antagonists for paclitaxel-refractory cancer.Pharmaceutical research · 2012Article
Corrections and comments
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Authors and funding
12 authors at 6 institutions in 2 countries.
Funding
Abstract
purposeTo describe the pharmacokinetics of orally administered ABT-751 and its conjugated metabolites in children with neuroblastoma and other solid tumors and to relate pharmacokinetic parameters to toxicity and therapeutic outcomes.
methodsPatients (median age, 11 years) with neuroblastoma (n = 37) or other solid tumors (n = 25) had pharmacokinetic sampling after the first dose of ABT-751 (75-250 mg/m(2)/day) on a 7-day or 21-day schedule. ABT-751 and its glucuronide and sulfate metabolites were quantified with an HPLC/MS/MS assay. Pharmacokinetic parameters were derived with non-compartmental methods. The relative bioavailability of more water soluble capsule and suspension formulations was assessed.
resultsABT-751 peaked in plasma at 2 h and declined monoexponentially with a t (1/2) of 5.1 h. The apparent clearance was 33 ml/min/m(2) and was age-independent. The AUC(0-infinity) increased in proportion to the dose, and at 200 mg/m(2) the median AUC(0-infinity) was 91 mcg h/ml and the C (ave) was 3.9 mcg/ml. Inter-and intra-patient variability was low. The metabolites were detected in plasma 30 min post-dose and peaked 3-5 h after the dose. The glucuronide:sulfate molar AUC(0-infinity) ratio was 0.57. Less than 1% of the dose was excreted in urine as parent drug; 13% of the dose was excreted as sulfate metabolite and 10% as glucuronide metabolite. The relative bioavailability of the water soluble capsule and suspension formulations was 105 and 93%, respectively. AUC(0-infinity) was higher in patients experiencing dose-limiting toxicity.
conclusionsOral ABT-751 pharmacokinetics was dose-proportional and age-independent with minimal intra- and inter-patient variability in children.
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Registered trials
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