PHARMACOKINETICS AND TOLERANCE OF NICOTINAMIDE COMBINED WITH RADIATION-THERAPY IN PATIENTS WITH GLIOBLASTOMA-MULTIFORME

The pharmacokinetic properties of nicotinamide and its tolerance were studied in seven patients affected by glioblastoma multiforme and treated with two fractions per day of radiation therapy. Nicotinamide was given orally at two daily doses of 4 g and then 2 g separated by a 6-h-interval. The treatment was well tolerated in almost all patients and had no effect on blood pressure, cardiac rhythm or body temperature. Pharmacokinetic analysis showed peak plasma levels (C-max) above 100 mg/l 45 minutes after the administration of both doses. This was followed by a biexponential decay of plasma concentrations with a thermal half life of 9.4 h. Tumours were irradiated 1 hour after each drug dose to match with drug C-max in plasma, and although it is too early to evaluate the tumour response, the drug levels achieved should be sufficient to improve radiation therapy.