A phase I and pharmacokinetic study of didox administered by 36 hour infusion. The Cancer Research Campaign Phase I/II Clinical Trials Committee
| Autor: | Carmichael, J., Cantwell, B. M., Mannix, K. A., Veale, D., Elford, H. L., Blackie, R., Kerr, D. J., Kaye, S. B., Harris, A. L. |
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| Jazyk: | angličtina |
| Rok vydání: | 1990 |
| Předmět: | |
| Zdroj: | British Journal of Cancer |
| ISSN: | 1532-1827 0007-0920 |
| Popis: | Twelve patients were treated with didox, a new ribonucleotide reductase inhibitor, by 36 h infusion. The maximum tolerated dose was 6 g m-2, above which dose-limiting hepatic toxicity was observed. Patient tolerance was significantly better using the 36 h infusion compared to patients receiving the drug by a 30 min infusion; in particular, there were no reports of nausea or vomiting. No responses were seen in these patients. Detailed pharmacokinetics were performed at 6 g m-2 comparing the 36 h and 30 min infusions in four patients. Parent drug AUC values were lower for the 36 h infusion, 67.8 micrograms ml-1 h-1 compared to 232 micrograms ml-1 h-1 for the 30 min infusion. AUC values for the 3-hydroxy metabolite were much higher following the 36 h infusion: 55.4 compared to 18.6 micrograms ml-1 h-1. In contrast, the amide metabolite was not detected following the 36 h infusion, but AUC values of 23 micrograms ml-1 h-1 were seen after the 30 min infusion. The mean peak plasma level was 72 micrograms ml-1 following 6 g m-2 given by a 30 min infusion compared to 2.8 micrograms ml-1 following the prolonged infusion. Clearance was higher following the 36 h infusion: 97.6 versus 24.4 l h-1. |
| Databáze: | OpenAIRE |
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