NICOTINAMIDE PHARMACOKINETICS IN HUMANS AND MICE - A COMPARATIVE-ASSESSMENT AND THE IMPLICATIONS FOR RADIOTHERAPY

Healthy human volunteers orally ingested escalating doses of up to 6 g nicotinamide in capsule form on an empty stomach. Some side-effects w ere seen although these were mild and transient. HPLC analysis of bloo d samples showed peak plasma levels, typically within 45 min after ing estion, which were linearly dependent on dose ingested. The eliminatio n half-life and AUC were also found to increase with drug dose, althou gh these increases were non-linear. Pharmacokinetic studies were also performed in female CDF1 mice with C3H mammary carcinomas grown in the right rear foot. Analysis of blood and tumour samples taken from mice injected i.p. with nicotinamide doses between 100-1000 mg/kg showed s imilar characteristics as the human data, although the elimination hal f-lives were not dose-dependent. The average peak plasma concentration of 160 mug/ml measured in humans after taking 6 g of nicotinamide was equivalent to that seen in mice after injecting 171 mg/kg. Using a re growth delay assay the enhancement of radiation damage by nicotinamide in this mouse tumour was found to be independent of drug dose from 10 0-1000 mg/kg, resulting in a constant 1.3-fold increase in radiation r esponse. Doses of nicotinamide that can be tolerated clinically should therefore produce adequate enhancements of radiation damage in human tumours.