title: In vitro binding and partitioning of irinotecan (CPT-11) and its metabolite, SN-38, in human blood.
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).
authors.affiliation: Laboratoire de Pharmacologie, Faculté de Médecine, Créteil, France.
authors.forename: O
authors.initials: O
authors.lastname: Combes
authors.forename: J
authors.initials: J
authors.lastname: Barré
authors.forename: J C
authors.initials: JC
authors.lastname: Duché
authors.forename: L
authors.initials: L
authors.lastname: Vernillet
authors.forename: Y
authors.initials: Y
authors.lastname: Archimbaud
authors.forename: M P
authors.initials: MP
authors.lastname: Marietta
authors.forename: J P
authors.initials: JP
authors.lastname: Tillement
authors.forename: S
authors.initials: S
authors.lastname: Urien
mesh_terms: D000972:Antineoplastic Agents, Phytogenic / Q000097:blood / Q000493:pharmacokinetics*; D001772:Blood Cell Count; D001773:Blood Cells / Q000378:metabolism; D001792:Blood Platelets / Q000378:metabolism; D001798:Blood Proteins / Q000378:metabolism; D002166:Camptothecin / Q000031:analogs & derivatives* / Q000097:blood / Q000493:pharmacokinetics; D006801:Humans; D066298:In Vitro Techniques; D000077146:Irinotecan; D011485:Protein Binding; D014462:Ultrafiltration
chemical_list: D000972:Antineoplastic Agents, Phytogenic; D001798:Blood Proteins; D000077146:Irinotecan; D002166:Camptothecin