Pretreatment H2 receptor antagonists that differ in P450 modulation activity: comparative effects on paclitaxel clearance rates and neutropenia.

摘要: Histamine-2 receptor antagonists (H2RAs) are principal components of the premedication regimen used to prevent major hypersensitivity reactions in patients receiving paclitaxel. Several different H2RAs, including cimetidine, ranitidine and famotidine, have been clinical trials paclitaxel, as well by clinicians geographic regions hospitals primarily because differences availability various H2RAs. However, H2RAs highly variable cytochrome P450-modulating capabilities, P450 system appears play a role paclitaxel metabolism disposition. Therefore, use may result pharmacologic, toxicologic antitumor profiles due differential effects on metabolism. This study evaluated whether cimetidine which possess disparate differentially affect clearance rates agent's toxicity, neutropenia. Women with advanced, platinum-refractory ovarian carcinoma received two courses treatment 135 mg/m2 over 24 h while participating National Cancer Institute's Treatment Referral Center Protocol. A crossover design was employed consecutive either 300 mg i.v. or 20 famotidine before their first course alternate H2RA second course. In order evaluate pertinent pharmacologic parameters same individual, concentrations at steady-state (Css), rates, absolute neutrophil counts (ANCs) were obtained during both courses. Paclitaxel Css values not significantly individual when preceded (p=0.16). Mean 271 243 ml/min per m2 following respectively. These paired analysis (p=0.30). The likelihood subsequently requiring granulocyte-colony stimulating factor (G-CSF) for severe neutropenia 1 did differ between (p=0.9). Among who require G-CSF, mean percentage decreases ANC 87.7% 84.2% after cycles measures (p=0.13). results show that do toxicity reactions, be interchanged.