HOMEPRODUCTSCOMPANYCONTACTFAQResearchDictionaryPharmaSign Up FREE or Login

Evaluation of limited blood sampling in a preceding 99mTc-labeled diagnostic study to predict the pharmacokinetics and myelotoxicity of 186Re-cMAb U36 radioimmunotherapy.

AbstractUNLABELLED:
186Re-labeled chimeric monoclonal antibody U36 (cMAb U36) was recently evaluated in a phase I dose escalation study in head and neck cancer patients. All 13 patients received 99mTc-labeled cMAb U36 before 186Re-cMAb U36 radioimmunotherapy. The aim of this study was to evaluate the suitability of multiple or limited blood sampling to predict clearance, red marrow absorbed dose, and myelotoxicity of 186Re-cMAb U36.
METHODS:
Population pharmacokinetics of 186Re-cMAb U36 were analyzed with a nonparametric expectation algorithm (NPEM 2) and used for Bayesian analysis of individual patient data to predict cMAb U36 clearance.
RESULTS:
186Re-cMAb U36 clearance was most accurately predicted (r = 0.91, P < 0.001) with limited sampling for sample points 4 and 72 h after administration of 186Re-cMAb U36. These predictions were less accurate with 99mTc-cMAb U36 (r = 0.51, P = 0.078 for multiple sampling; r = 0.47, P = 0.104 for sampling at 4 and 21 h after administration). Thrombocytopenia was found to be correlated with the red marrow absorbed dose and was equally well predicted by limited blood sampling after administration of 99mTc-cMAb U36 (r = 0.81, P < 0.01) or 186Re-cMAb U36 (r = 0.79, P < 0.01).
CONCLUSION:
Limited sampling seems useful to predict pharmacokinetics and myelotoxicity of 186Re-cMAb U36.
AuthorsD R Colnot, A J Wilhelm, J Cloos, J C Roos, R de Bree, J J Quak, G B Snow, G A van Dongen
JournalJournal of nuclear medicine : official publication, Society of Nuclear Medicine (J Nucl Med) Vol. 42 Issue 9 Pg. 1364-7 (Sep 2001) ISSN: 0161-5505 [Print] United States
PMID11535726 (Publication Type: Evaluation Study, Journal Article, Research Support, Non-U.S. Gov't)
Chemical References
  • Antibodies, Monoclonal
  • Radioisotopes
  • Recombinant Fusion Proteins
  • Rhenium
Topics
  • Aged
  • Algorithms
  • Antibodies, Monoclonal (adverse effects, immunology, pharmacokinetics, therapeutic use)
  • Area Under Curve
  • Bayes Theorem
  • Bone Marrow (radiation effects)
  • Female
  • Head and Neck Neoplasms (radiotherapy)
  • Humans
  • Male
  • Middle Aged
  • Predictive Value of Tests
  • Radioimmunotherapy (adverse effects)
  • Radioisotopes (adverse effects, pharmacokinetics, therapeutic use)
  • Radiotherapy Dosage
  • Recombinant Fusion Proteins
  • Regression Analysis
  • Rhenium (adverse effects, pharmacokinetics, therapeutic use)
  • Thrombocytopenia (etiology)

Join CureHunter, for free Research Interface BASIC access!

Take advantage of free CureHunter research engine access to explore the best drug and treatment options for any disease. Find out why thousands of doctors, pharma researchers and patient activists around the world use CureHunter every day.
Realize the full power of the drug-disease research graph!


Choose Username:
Email:
Password:
Verify Password:
Enter Code Shown: