Administration of nicotinamide during a five- to seven-week course of radiotherapy: pharmacokinetics, tolerance, and compliance

Abstract

Background and purpose: Nicotinamide was administered daily as a liquid formulation to head and neck cancer patients receiving a 5-to 7-week course of radiotherapy. The pharmacokinetics, compliance, and tolerance of this drug formulation were studied.Materials and methods: Blood 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 the first and last full weeks of the treatment. Side-effects of nicotinamide were monitored.Results: In all patients peak concentrations greater 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 decreased to 59% in the last week of treatment which can be partly attributed to reduced compliance. The most important side-effect of nicotinamide was nausea with or without vomiting occurring in 65% of the patients. Severe side-effects were associated with high plasma concen trations over subsequent days. Tolerance improved after a 25% reduction of dose in six of seven patients but plasma levels at the time of irradiation fell below 700 nmol/ml in four out of six of these patients.Conclusions: Peak plasma concentrations above the 700 nmol/ml level were obtained in all patients but these concentrations could not be reproduced during the entire course of the treatment in a significant portion of the subjects. Side-effects of nicotinamide are associated with plasma concentrations and tolerance can be improved by a moderate reduction of dose.

C/EBPε mediates nicotinamide-enhanced clearance of Staphylococcus aureus in mice

“…In human trials, NAM is frequently administered as a modifier to patients undergoing radiotherapy (47,48,57,58). In these trials, a plasma concentration of 1 mM NAM is routinely achieved, a concentration that we used in our peripheral whole blood killing assays to demonstrate NAM efficacy.…”

Role of Nicotinamide in DNA Damage, Mutagenesis, and DNA Repair

“…Systemic absorption of topical nicotinamide has been reported to be approximately 10% depending on the vehicle used [7]. Adverse effects of nicotinamide are rare and have occurred mainly with high oral doses (≥6 gram/day), which include nausea, vomiting, liver toxicity, headache, fatigue, and dizziness [8–10]. Unlike niacin, nicotinamide is not a vasodilator, thus it rarely causes flushing [11].…”

Effect of a Topical Vasodilator on Tumor Hypoxia and Tumor Oxygen Guided Radiotherapy using EPR Oximetry

“…Nicotinamide was used in these studies because it was thought to be a fairly non-toxic drug, but a daily administration of 80 mg/kg nicotinamide during radiotherapy caused nausea and vomiting in most patients (19). Over 30% of the patients discontinued use due to these side effects, which were generally unresponsive to antiemetic drugs (20, 21). Other nicotinate derivatives also have been investigated to achieve better tumor oxygenation to enhance radio-therapeutic response (22, 23).…”