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OtherDEVELOPMENTAL PHARMACOLOGY

Propranolol Elimination by Right and Left Fetal Liver: Studies in the Intact Isolated Perfused Fetal Sheep Liver

John A. Ring, Hany Ghabrial, Michael S. Ching, Arthur Shulkes, Richard A. Smallwood and Denis J. Morgan
Journal of Pharmacology and Experimental Therapeutics February 1998, 284 (2) 535-541;
John A. Ring
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Hany Ghabrial
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Michael S. Ching
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Arthur Shulkes
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Abstract

Propranolol extraction in vivo by the left lobe of the fetal sheep liver is greater than that by the right lobe, and this may be due to the fact that oxygenation of the left lobe is greater than that of the right lobe. To explore this hypothesis, we studied the elimination of (R)-(+)-propranolol (PROP) by right and left lobes of the intact isolated perfused fetal sheep liver model, in which there is equal oxygenation of both liver lobes. After isolation of the liver, near-term fetal sheep livers (n = 11) were perfused (2.68 ± 1.05 ml/g liver/min) in situvia the umbilical vein in a 1-liter recirculating system. PROP was infused (1.2 mg/hr) into the reservoir after an initial bolus dose (2.3 mg). Perfusate samples were taken from the common and right and left hepatic veins every 10 min for determination of PROP concentrations and oxygen consumption over the 180-min experimental period. Mean ductus venosus shunt through the liver was 42 ± 21% of perfusate flow. Oxygen consumption was not significantly different between the left and right lobes of the liver (0.79 ± 0.46 and 0.67 ± 0.44 μmol/g liver/min, respectively, P > .05), nor was there any significant difference between lobes in PROP hepatic extraction at steady state (0.25 ± 0.20 and 0.25 ± 0.23, respectively, P > .05). This supports the hypothesis that the difference between lobes in PROP extractionin vivo may be due to the difference in degree of oxygenation of the left and right lobes that is known to be presentin vivo.

Footnotes

  • Send reprint requests to: Dr. D. J. Morgan, Department of Pharmaceutics, Victorian College of Pharmacy, Monash University, 381 Royal Parade, Parkville, Victoria 3052, Australia.

  • ↵1 This work was supported by the National Health and Medical Research Council of Australia (NHMRC) and the Clive and Vera Ramaciotti Foundation.

  • ↵2 J.A.R. was supported by a Gastroenterological Society of Australia Post Graduate Research Scholarship sponsored by Glaxo Australia Pty. Ltd.

  • ↵3 M.S.C. is a Senior Research Officer funded by the NHMRC (Australia).

  • ↵4 A.S. is an NHMRC (Australia) Senior Principal Research Fellow.

  • Abbreviations:
    PROP
    (R)-(+)-propranolol hydrochloride
    Cl
    clearance
    Q
    flow rate
    E
    extraction ratio
    Ocon
    oxygen consumption
    • Received April 17, 1997.
    • Accepted October 15, 1997.
  • The American Society for Pharmacology and Experimental Therapeutics
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Journal of Pharmacology and Experimental Therapeutics
Vol. 284, Issue 2
1 Feb 1998
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OtherDEVELOPMENTAL PHARMACOLOGY

Propranolol Elimination by Right and Left Fetal Liver: Studies in the Intact Isolated Perfused Fetal Sheep Liver

John A. Ring, Hany Ghabrial, Michael S. Ching, Arthur Shulkes, Richard A. Smallwood and Denis J. Morgan
Journal of Pharmacology and Experimental Therapeutics February 1, 1998, 284 (2) 535-541;

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Propranolol Elimination by Right and Left Fetal Liver: Studies in the Intact Isolated Perfused Fetal Sheep Liver

John A. Ring, Hany Ghabrial, Michael S. Ching, Arthur Shulkes, Richard A. Smallwood and Denis J. Morgan
Journal of Pharmacology and Experimental Therapeutics February 1, 1998, 284 (2) 535-541;
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