Abstract：
AIM:Chemotherapy with indisulam causes myelosuppression. This study aimed to evaluate the influence of patient-related covariates on pharmacokinetics and pharmacodynamics, to identify patients at risk for severe myelosuppression and to develop a dosing algorithm for treatment optimization. METHODS:Pharmacokinetic and pharmacodynamic data of 412 patients were available. Non-linear mixed effects modeling was used to determine the relative risk of dose-limiting myelosuppression for various covariates (demographics, physical condition, prior treatment, comedication, CYP2C genotype and biochemistry). RESULTS:Body surface area (BSA), race and CYP2C genotype had a significant impact on indisulam elimination (P < 0.001). Low BSA, Japanese race, variant CYP2C genotype, low baseline neutrophil and thrombocyte counts and female sex were clinically relevant risk factors of dose-limiting myelosuppression (RR > 1.1). A dosing strategy was developed to optimize treatment for patient subgroups. CONCLUSIONS:This study has identified covariates related to an increased risk of myelosuppression after indisulam therapy. Dose individualization may contribute to treatment optimization.
journal_name
J Pharmacokinet Pharmacodynjournal_title
Journal of pharmacokinetics and pharmacodynamicsauthors
Zandvliet AS,Schellens JH,Copalu W,Beijnen JH,Huitema ADdoi
10.1007/s10928-009-9111-2subject
Has Abstractpub_date
2009-02-01 00:00:00pages
39-62issue
1eissn
1567-567Xissn
1573-8744journal_volume
36pub_type
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