1. Academic Validation
  2. Histamine pharmacokinetics in tumor and host tissues after bolus-dose administration in the rat

Histamine pharmacokinetics in tumor and host tissues after bolus-dose administration in the rat

  • Life Sci. 2002 Jan 11;70(8):969-76. doi: 10.1016/s0024-3205(01)01468-0.
Magnus Rizell 1 Peter Naredi Per Lindnér Kristoffer Hellstrand Mark Sarno Per-Anders Jansson
Affiliations

Affiliation

  • 1 Department of Surgery, Sahlgrenska University Hospital, Gothenburg, Sweden. magnus.rizell@surgery.gu.se
Abstract

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.

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