Plasma concentrations and urinary excretion of histamine after inhalation and subcutaneous injection of histamine.
1. Increased histamine concentrations are found in the plasma and urine following allergen challenge in allergic subjects. This study compared a controlled challenge with clinically relevant doses of inhaled and injected histamine, as indicative of an allergic response, in an attempt to validate the use of urinary histamine or 1-methylhistamine measurements as an objective, non-invasive diagnostic test. 2. Inhalation of histamine produced peripheral vasodilation, increased heart rate, a fall in partial expiratory flow rate (pEFR) and blood pressure, 'tight chest' and cough. Subcutaneous injection produced vasodilation and headache but no change in heart rate or blood pressure. 3. Plasma histamine concentrations were similar in the two studies. Inhalation of increasing doses of histamine through a nebuliser (output 0.13 ml min-1) resulted in an increase from a mean of 0.30 to 1.65 ng ml-1, with return towards baseline within 20 min. Injection of 1 mg histamine s.c. produced an increase from 0.32 to 1.4 ng ml-1 within 5 min, remaining above 1 ng ml-1 for 30 min. 4. There was a significant increase of 15.2 ng mg-1 creatinine in urinary histamine concentration following the injection of histamine (P = 0.04) and an increase of 11.4 ng mg-1 creatinine when histamine was given by inhalation (P = 0.18). Histamine excretion rate increased by 108 ng min-1 (P = 0.04) after inhalation and by 37.2 ng min-1 (P = 0.09) after injection. Urinary 1-methylhistamine concentrations were significantly raised following both histamine inhalation (+ 238 ng mg-1 creatinine; P = 0.013) and injection (+ 180 ng mg-1 creatinine; P = 0.03).(ABSTRACT TRUNCATED AT 250 WORDS)
Murdoch
R D
RD
Clinical Pharmacology Unit, SmithKline Beecham Pharmaceuticals, Harlow, Essex.
Youlten
L J
LJ
Williams
A J
AJ
Howland
K
K
D000280:Administration, Inhalation; D000328:Adult; D000485:Allergens; D001794:Blood Pressure / Q000187:drug effects; D001985:Bronchial Provocation Tests; D003371:Cough / Q000139:chemically induced; D005541:Forced Expiratory Volume / Q000187:drug effects; D006261:Headache / Q000139:chemically induced; D006339:Heart Rate / Q000187:drug effects; D006632:Histamine / Q000008:administration & dosage / Q000097:blood / Q000494:pharmacology / Q000652:urine*; D006801:Humans; D007279:Injections, Subcutaneous; D008297:Male; D008761:Methylhistamines / Q000652:urine; D008875:Middle Aged; D010366:Peak Expiratory Flow Rate / Q000187:drug effects; D014664:Vasodilation / Q000187:drug effects
D000485:Allergens; D008761:Methylhistamines; D006632:Histamine; C048140:N-methylhistamine