title: Administration of nicotinamide during a five- to seven-week course of radiotherapy: pharmacokinetics, tolerance, and compliance.
abstract: OBJECTIVE
  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.
  
  
  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 concentrations 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.
authors.affiliation: Institute of Radiotherapy, University of Nijmegen, The Netherlands.
authors.forename: J H
authors.initials: JH
authors.lastname: Kaanders
authors.forename: M R
authors.initials: MR
authors.lastname: Stratford
authors.forename: J
authors.initials: J
authors.lastname: Liefers
authors.forename: M F
authors.initials: MF
authors.lastname: Dennis
authors.forename: A J
authors.initials: AJ
authors.lastname: van der Kogel
authors.forename: W A
authors.initials: WA
authors.lastname: van Daal
authors.forename: A
authors.initials: A
authors.lastname: Rojas
mesh_terms: D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D004305:Dose-Response Relationship, Drug; D005260:Female; D006258:Head and Neck Neoplasms / Q000378:metabolism / Q000532:radiotherapy*; D006801:Humans; D008297:Male; D008875:Middle Aged; D009536:Niacinamide / Q000009:adverse effects / Q000493:pharmacokinetics*; D010349:Patient Compliance
chemical_list: D009536:Niacinamide