ADMINISTRATION OF NICOTINAMIDE DURING A 5 TO 7-WEEK COURSE OF RADIOTHERAPY - PHARMACOKINETICS, TOLERANCE, AND COMPLIANCE

Background and purpose: Nicotinamide was administered daily as a liqui d formulation to head and neck cancer patients receiving a 5- to 7-wee k course of radiotherapy. The pharmacokinetics, compliance, and tolera nce of this drug formulation were studied. Materials and methods: Bloo d samples were drawn and nicotinamide levels determined in 40 head and neck cancer patients. On the first treatment day serial samples were obtained followed by daily samples at the time of irradiation during t he first and last full weeks of the treatment. Side-effects of nicotin amide were monitored. Results: In all patients peak concentrations gre ater than 700 nmol/ml could be obtained 0.25-3 h (mean 0.83 +/- 0.73 h ) after drug intake. During the first week of treatment plasma levels at the time of irradiation were adequate in 82% of the samples. This d ecreased to 59% in the last week of treatment which can be partly attr ibuted to reduced compliance. The most important side-effect of nicoti namide was nausea with or without vomiting occurring in 65% of the pat ients. Severe side-effects were associated with high plasma concentrat ions over subsequent days. Tolerance improved after a 25% reduction of dose in six of seven patients but plasma levels at the time of irradi ation fell below 700 nmol/ml in four out of six of these patients. Con clusions: Peak plasma concentrations above the 700 nmol/ml level were obtained in all patients but these concentrations could not be reprodu ced during the entire course of the treatment in a significant portion of the subjects. Side-effects of nicotinamide are associated with pla sma concentrations and tolerance can be improved by a moderate reducti on of dose. (C) 1997 Elsevier Science B.V.