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Effects of Pringle Maneuver and Partial Hepatectomy on the Systemic Pharmacokinetics of Fluorescein in Rats
Author(s) -
Kowser Mohammad,
Shaik Imam,
Bickel Ulrich,
Mehvar Reza
Publication year - 2015
Publication title -
the faseb journal
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.709
H-Index - 277
eISSN - 1530-6860
pISSN - 0892-6638
DOI - 10.1096/fasebj.29.1_supplement.779.12
Subject(s) - pharmacokinetics , hepatectomy , analysis of variance , blood flow , metabolite , medicine , chemistry , anesthesia , surgery , resection
The purpose of this study was to determine the effects of hepatic ischemia‐reperfusion injury (Pringle maneuver) and/or partial hepatectomy (Hx) on the systemic pharmacokinetics of fluorescein (FL). Rats underwent Pringle maneuver (complete occlusion of hepatic blood supply) for 20 min (IR) or Pringle maneuver plus partital (70%) hepatectomy (HxIR) (n=6/group). Sham‐operated animals (Sham, n = 7) underwent laparotomy without IR or Hx. Approximately 15 min after reinstatement of blood flow, a single 25‐mg/kg dose of FL was injected into the penile vein, and serial blood, cumulative bile (0‐30 min), and terminal liver (30 min) samples were collected. The concentrations of FL and its glucuronidated metabolite (FL‐Glu) in the samples were determined by HPLC, and relevant pharmacokinetic parameters were determined. Statistical analysis was by ANOVA, followed by Tukey's test. HxIR, but not IR alone, caused significant increases in the FL plasma AUC (40%, P < 0.05) and plasma free fraction (75%, P < 0.01), compared with the Sham animals. Additionally, the biliary recovery of FL was reduced (P < 0.001) by 89% and 73% in the HxIR and IR animals, respectively. Similar reductions were also noted for the biliary recovery of FL‐Glu. Furthermore, the bile flow rates in the IR and HxIR groups were, respectively, 61% and 73% lower than those in the Sham group. Indeed, there were significant correlations between the biliary recovery of FL or FL‐Glu and the bile flow rate with r 2 values of 0.929 or 0.938, respectively. In conclusion, IR and HxIR alter the systemic pharmacokinetics of Flu in rats.