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In Vitro Binding and Partitioning of Irinotecan (CPT-11) and its Metabolite, SN-38, in Human Blood
- Source :
- Investigational New Drugs. 18:1-5
- Publication Year :
- 2000
- Publisher :
- Springer Science and Business Media LLC, 2000.
-
Abstract
- The binding of CPT-11 and SN-38 to human plasma proteins was studied by ultrafiltration at 37 degrees C and pH 7.4. In plasma, CPT-11 was 66-60% bound in the range 100-4000 ng/ml and SN-38 was 94-96% bound in the range 50-200 ng/ml. At these concentrations the plasma binding of CPT-11 was slightly saturable, but the plasma binding of SN-38 was concentration-independent. Albumin was the main carrier of CPT-11 and SN-38 in plasma. In blood, the binding of CPT-11 was moderate (80%), mainly to plasma proteins (47%) and erythrocytes (33%). The binding of SN-38 was high (99%) and most of SN-38 in blood was located in blood cells (approximately 66%) The simulation of a grade 3 hematotoxicity (according to National Cancer Institute's Common Toxicity Criteria grading) on the SN-38 blood distribution yielded an increase in fu (free fraction of drug in plasma) from 1.05 to 2.08 and a decrease in C(Bl)/C(P) from 1.66 to 1.14 (both resulting from a decreased cell binding).
- Subjects :
- Blood Platelets
Ultrafiltration
SN-38
Plasma protein binding
In Vitro Techniques
Irinotecan
Blood cell
chemistry.chemical_compound
Blood plasma
medicine
Humans
Pharmacology (medical)
Pharmacology
Blood Cells
Chromatography
Albumin
Blood Proteins
Antineoplastic Agents, Phytogenic
Blood proteins
Blood Cell Count
Red blood cell
medicine.anatomical_structure
Oncology
chemistry
Biochemistry
Free fraction
Camptothecin
Protein Binding
Subjects
Details
- ISSN :
- 15730646 and 01676997
- Volume :
- 18
- Database :
- OpenAIRE
- Journal :
- Investigational New Drugs
- Accession number :
- edsair.doi.dedup.....740405ef4c48ad5cd84e20f618333726