AI Article Synopsis
- This study investigated the pharmacokinetic (PK) and pharmacodynamic (PD) relationships of amrubicin and its metabolite amrubicinol in Japanese lung cancer patients, aiming to clarify their full PK profiles.
- Amrubicin was administered to 21 patients, with blood samples taken to measure drug levels and analyze their correlation with hematological toxicities.
- The findings showed that the PK profiles of both drugs were accurately characterized, and the clearance of amrubicinol was significantly linked to severe neutropenia, indicating its critical role in determining this toxic effect.
Article Abstract
Purpose: The pharmacokinetic (PK)-pharmacodynamic (PD) relationship of amrubicin and its active metabolite, amrubicinol, has only been evaluated using trough levels of these agents since the full PK profiles not yet been clarified so far. This study was performed to analyze the full PK profiles of amrubicin and amrubicinol and to evaluate their toxicity-PK relationships in Japanese patients.
Methods: Amrubicin (35-40 mg/m(2)) was administered to 21 lung cancer patients on days 1-3 every 3-4 weeks. Fourteen blood samples were obtained per patient over the course of 3 administration days. The plasma concentrations of amrubicin and amrubicinol were quantitated by HPLC, and the relationships between PK parameters of these compounds and hematological toxicities were evaluated.
Results: The overall PK profiles of amrubicin and amrubicinol were well characterized using a 3-compartment model and a 1-compartment model with a first-order metabolic process, respectively. The major toxicities were hematological. The clearance of amrubicinol was significantly correlated with grade 4 neutropenia (P = 0.01). The percentage decreases in the neutrophil count, hemoglobin level and platelet count were well correlated with the amrubicinol AUC.
Conclusion: The pharmacokinetic profiles of amrubicin and amrubicinol were clarified, and the subsequent PK-PD analyses indicate that the clearance of amrubicinol is the major determinant of neutropenia.
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| http://dx.doi.org/10.1007/s00280-011-1768-8 | DOI Listing |
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