Carmustine pharmacokinetics

Despite the fact that alkylating agents exhibit a common mechanism of action, their clinical use varies depending on differences in pharmacokinetics, metabolism, hpid solubility, ability to penetrate membranes, and toxicity. They can be classified as nitrogen-containing mustard derivatives (mechorethamine, chlorambucil, melfalan, cyclophosphamide, ifos-famide), derivatives of ethylenimine (thiotepa), nitrosoureas (carmustine, lomustine, strep-tozocin), alkylsulfonates (busulfan), and derivatives of platinum (cwplatin, carboplatin). 

Pharmacokinetics In spite of the similarities in their structures, carmustine is administered intravenously, whereas lomustine is... 

Pharmacokinetics Only available as IV Mechlorethamine IV only Carmustine renally cleared. Busulfan may give IV or PO ... 

Fung LK, Ewend MG, AiUs A, Sipos EP, Thompson R, Watts M, Colvin OM, Brem H, Saltzman WM (1998) Pharmacokinetics of interstitial delivery of carmustine, 4-hydroperoxy-cyclophosphamide, and paclitaxel from a biodegradable polymer implant in the monkey brain. Cancer Res 58 672-684. 

Some evidence su ests ondansetron may modestly affect the pharmacokinetics of cyclophosphamide and cisplatin but it does not appear to affect those of carmustine. Ondansetron did not affect the in vitro activity of epirubicin, bleomycin, cisplatin or es-tramustine. Cisplatin and fluorouracil do not affect the pharmacokinetics of ondansetron. In in vitro studies granisetron potentiated the cytotoxic effects of epirubicin, had an additive effect on bleomycin and estramustine activity and appeared not to affect the metabolism of docetaxel and paclitaxel. 

The pharmacokinetics of high-dose cyclophosphamide, cisplatin and carmustine in 23 patients given ondansetron, lorazepam and diphenhydramine as antiemetics were compared with those in 129 patients who received prochlorperazine instead of ondansetron. It was found that the AUCs of cyclophosphamide and cisplatin, but not that of carmustine, were significantly lower (by 15% and 19%, respectively) in the ondansetron group. Similarly, in another study, the pharmacokinetics of antineoplastics were analysed in 54 patients with breast cancer who were receiving high-dose cyclophosphamide, cisplatin and carmustine with lorazepam and ondansetron with or without prochlorperazine and com-... 

Fleming AB, Saltzman WM. Pharmacokinetics of the carmustine implant. Clin Pharmacokinet 2002 41 403-419. 

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