The modification of human tumour blood flow using pentoxifylline, nicotinamide and carbogen.
OBJECTIVE
To assess the effect of combining oral nicotinamide, oral pentoxifylline and carbogen gas (2% CO2, 98% O2) breathing on human tumour red cell flux.


METHODS
Microregional red blood cell flux was measured in accessible tumour nodules using laser Doppler microprobes in 11 patients with histologically proven malignancy. Patients received single oral doses of nicotinamide 40 mgkg-1 and pentoxifylline 1200 mg 2h before a 10-min period of carbogen gas breathing, corresponding to peak plasma concentrations of these drugs. Red cell flux in up to six microregions in each tumour was measured for 30 min, recording pre-, during and post-carbogen breathing for 10 min each.


RESULTS
Data from ten of the 11 patients could be assessed. The red cell flux in 48 microregions was analysed and the mean red cell flux was calculated. A mean relative increase in red cell flux of 1.18 (+/-0.09, 95% confidence interval (CI)) was observed after 6 min of carbogen breathing, 2h after the administration of nicotinamide and pentoxifylline. This compares to relative increases of 1.4 (+/-0.39, 95%CI) after nicotinamide with carbogen and 1.15 (+/-0.10, 95%CI) after pentoxifylline with carbogen. These differences are not statistically significant (P>0.05). The increased red cell flux persisted after the cessation of carbogen gas breathing.


CONCLUSIONS
A combination of pentoxifylline, nicotinamide and carbogen produces an increase in human tumour red cell flux, similar to that observed when each of the drugs are used alone with carbogen breathing.
Sibtain
Amen
A
Marie Curie Research Wing, Mount Vernon Hospital, Rickmansworth Road, Northwood, Middlesex HA6 2RN, UK.
Hill
Sally
S
Goodchild
Kate
K
Shah
Nihal
N
Saunders
Michele
M
Hoskin
Peter J
PJ
D000280:Administration, Inhalation; D000284:Administration, Oral; D000328:Adult; D000368:Aged; D002245:Carbon Dioxide / Q000008:administration & dosage / Q000494:pharmacology*; D005260:Female; D006801:Humans; D017078:Laser-Doppler Flowmetry; D008297:Male; D008833:Microcirculation; D008875:Middle Aged; D009369:Neoplasms / Q000098:blood supply*; D009536:Niacinamide / Q000008:administration & dosage / Q000494:pharmacology*; D010100:Oxygen / Q000008:administration & dosage / Q000494:pharmacology*; D010431:Pentoxifylline / Q000008:administration & dosage / Q000494:pharmacology*; D011838:Radiation-Sensitizing Agents / Q000008:administration & dosage / Q000494:pharmacology*; D012039:Regional Blood Flow / Q000187:drug effects; D013997:Time Factors; D015854:Up-Regulation
D011838:Radiation-Sensitizing Agents; D002245:Carbon Dioxide; D009536:Niacinamide; C011700:carbogen; D010100:Oxygen; D010431:Pentoxifylline