Journal
LIFE SCIENCES
Volume 70, Issue 8, Pages 969-976Publisher
PERGAMON-ELSEVIER SCIENCE LTD
DOI: 10.1016/S0024-3205(01)01468-0
Keywords
histamine; microdialysis; pharmacokinetics
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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 (t1/2 AB 3.9-7.7 minutes) but maximum concentration (Cmax; nmol/l) of histamine was higher in liver (2388 +/- 357) than in subcutis (951 +/- 125) (p<0.01) and subcutaneous tumor (523 +/- 140) (p=0.01) arid, moreover, Cmax in liver tumor (1752 +/- 326) was higher than in subcutaneous tumor (p=0.01). The t1/2 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 C-14-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. (C) 2002 Elsevier Science Inc. All fights reserved.
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