Histamine pharmacokinetics in tumor and host tissues after bolus-dose administration in the rat.
In this study, we estimated interstitial histamine concentrations in normal and malignant tissues after a single intravenous (i.v.) injection of 0.5 mg/kg histamine dihydrochloride in the rat. The microdialysis technique was used to collect interstitial fluid from subcutis, liver and a NGW adenocarcinoma. Histamine was absorbed with equal efficiency to all tissues (t 1/2 AB 3.9-7.7 minutes) but maximum concentration (Cmax; nmol/l) of histamine was higher in liver (2,388 +/- 357) than in subcutis (951 +/- 125) (p < 0.01) and subcutaneous tumor (523 +/- 140) (p = 0.01) and, moreover, Cmax in liver tumor (1,752 +/- 326) was higher than in subcutaneous tumor (p = 0.01). The tl/2 elimination was significantly longer in subcutis and subcutaneous tumor than in liver and liver tumor. Area under the curve (AUC; mmol-min/l) for histamine was significantly lower in subcutaneous tumor (9.8 +/- 2.3) than in liver (17.6 +/- 1.9) (p = 0.03) and liver tumor (15.8 +/- 1.8) (p = 0.03). Local tissue blood flow as assessed by the 14C-ethanol method was not significantly altered by the histamine administration. In conclusion, after an i.v. injection of histamine dihydrochloride a higher maximum concentration and AUC of histamine was reached in liver and liver tumor than in subcutaneous tissues.
Rizell
Magnus
M
Department of Surgery, Sahlgrenska University Hospital, Gothenburg, Sweden. magnus.rizell@surgery.gu.se
Naredi
Peter
P
Lindnér
Per
P
Hellstrand
Kristoffer
K
Sarno
Mark
M
Jansson
Per-Anders
PA
D000230:Adenocarcinoma / Q000378:metabolism* / Q000503:physiopathology; D000818:Animals; D019540:Area Under Curve; D001783:Blood Flow Velocity; D005110:Extracellular Space / Q000378:metabolism; D006207:Half-Life; D006632:Histamine / Q000008:administration & dosage / Q000493:pharmacokinetics*; D007275:Injections, Intravenous; D008099:Liver / Q000378:metabolism* / Q000503:physiopathology; D008114:Liver Neoplasms, Experimental / Q000378:metabolism* / Q000503:physiopathology; D008297:Male; D009604:Nitrosoguanidines / Q000633:toxicity; D011863:Radioimmunoassay; D051381:Rats; D017208:Rats, Wistar; D012867:Skin / Q000378:metabolism* / Q000503:physiopathology; D014018:Tissue Distribution
D009604:Nitrosoguanidines; D006632:Histamine