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Title: Pharmacokinetic and pharmacodynamic mechanisms for reduced toxicity of CPT-11 by thalidomide and St John's wort
Keywords: CPT-11; Thalidomide; St. John's Wort; Toxicity; Pharmacokinetics; Pharmacodynamics
Issue Date: 21-Aug-2007
Citation: YANG XIAOXIA (2007-08-21). Pharmacokinetic and pharmacodynamic mechanisms for reduced toxicity of CPT-11 by thalidomide and St John's wort. ScholarBank@NUS Repository.
Abstract: Gastrointestinal toxicity and myelosuppression hinder the clinical use of CPT-11-based dose-intensified regimens. Clinical studies indicated that combination with thalidomide or St. Johna??s wort (SJW) alleviated CPT-11 induced toxicity. However, the underlying mechanisms involved are not fully understood. In this thesis, a rat model with dose-limiting toxicity profiles that are similar to those observed in patients was developed and used to study the modulations of thalidomide and SJW on CPT-11 induced toxicities. Furthermore, the underlying pharmacodynamic and pharmacokinetic components involved were explored using in vivo and in vitro models. The study demonstrated that coadministered thalidomide or SJW significantly ameliorated the gastrointestinal and hematological toxicities of CPT-11 in rats, with both pharmacodynamic and pharmacokinetic mechanisms involved. This study may provide some effective strategies to circumvent CPT-11 induced toxicities using anti-TNF-I? agents through the inhibition of pro-inflammatory cytokine expression and intestinal epithelial cellular apoptosis.
Appears in Collections:Ph.D Theses (Open)

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