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Radiother Oncol. 1995 Sep;36(3):225-8.

Nicotinamide pharmacokinetics in patients.

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1
Department of Radiation Oncology, Henry Ford Hospital, Detroit, MI 48202, USA.

Abstract

Pharmacokinetic analyses were performed on blood samples of 12 patients undergoing treatment with nicotinamide, hyperthermia and radiation therapy for a variety of recurrent/metastatic cancers. Escalating oral doses of 3, 4, 5, 6 and 10 g of nicotinamide showed a linear relationship between maximum recorded plasma concentrations and the dose in grams (correlation coefficient, r = 0.91). Maximum plasma levels were observed by 30 min in most patients ingesting up to 6 g of nicotinamide. In marked contrast, five out of six patients ingesting 10 g of nicotinamide demonstrated increasing plasma levels at least up to 3 h post-ingestion. Doses up to 6 g were well tolerated and resulted in average maximum recorded plasma levels (mean +/- 1 SEM) of 156.4 +/- 33.6 micrograms/ml. Doses of 10 g were generally not well tolerated, but a high plasma level was maintained on average for at least 4 h. Plasma concentrations of the above order have been previously associated with maximal enhancement of radiation damage in mouse tumor models. This suggests that radiosensitization can be expected to occur in human tumors following oral administration of a safe and well tolerated dose of 6 g. However, at higher doses (i.e., 10 g), the pharmacokinetics, and perhaps radiosensitization, may differ markedly.

PMID:
8532910
DOI:
10.1016/0167-8140(95)01581-z
[Indexed for MEDLINE]

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