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Research ArticleArticle

Distribution Kinetics of Salicylic Acid in the Dual-Perfused Rat Liver Preparation

Selma Sahin and Malcolm Rowland
Drug Metabolism and Disposition March 1999, 27 (3) 373-378;
Selma Sahin
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Malcolm Rowland
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Abstract

The hepatic distribution kinetics of salicylic acid was determined using a single-pass dual hepatic artery (HA) and portal vein (PV) perfused in situ rat liver preparation. Bolus doses of [14C]salicylic acid and of reference markers ([3H]-water and [14C]-sucrose) were injected in a random order into either the HA or PV and then, after an appropriate interval, into the alternate vessel. The hepatic outflow profile of [14C]salicylic acid displayed a characteristic sharp peak followed by a slower eluting tail, whereas sucrose and water displayed unimodal outflow profiles. The biphasic outflow profile indicates that the hepatic distribution of salicylic acid is not instantaneous but is limited by a permeability barrier. The in situ permeability surface area product for [14C]salicylic acid was 3.35 ± 0.26 ml/min/g for PV and 7.45 ± 1.50 ml/min/g for HA administration. Furthermore, theory dictates that hepatic uptake is influenced by both perfusion and permeability if effective permeability surface area product/blood flow ratio lies between the values of 0.06 and 7.0. Our estimates (3.0 for venous output and 6.7 for arterial input) indicate that hepatic uptake of salicylic acid is dependent on both perfusion and permeability. The volume terms were calculated using two different methods, standard and specific. Regardless of the compound and method, the volume of distribution after arterial administration was larger than that after venous administration. In addition, a volume of distribution approximately twice that of the total aqueous space (i.e., HA, 2.23 ± 0.13 versus 1.10 ± 0.07 ml/g; PV, 1.72 ± 0.16 versus 0.68 ± 0.04 ml/g) implies that salicylic acid has a significant affinity for hepatic tissue. A similar tissue-to-perfusate partition coefficient associated with HA and PV input (5.40 ± 0.38 versus 6.48 ± 0.56) indicates that affinity of salicylic acid for hepatic tissue is independent of the route of input.

Footnotes

  • Send reprint requests to: Dr. Selma Sahin, Hacettepe University, Faculty of Pharmacy, 06100 Ankara, Turkey. E-mail:selma{at}tr-net.net.tr.

  • We thank the Turkish Government for a studentship (S.S.); research supported by a grant from the Wellcome Trust.

  • Abbreviations used are::
    HA
    hepatic artery
    PV
    portal vein
    PS
    permeability-surface area product
    • Received August 19, 1997.
    • Accepted October 14, 1998.
  • The American Society for Pharmacology and Experimental Therapeutics
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Drug Metabolism and Disposition: 27 (3)
Drug Metabolism and Disposition
Vol. 27, Issue 3
1 Mar 1999
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Research ArticleArticle

Distribution Kinetics of Salicylic Acid in the Dual-Perfused Rat Liver Preparation

Selma Sahin and Malcolm Rowland
Drug Metabolism and Disposition March 1, 1999, 27 (3) 373-378;

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Research ArticleArticle

Distribution Kinetics of Salicylic Acid in the Dual-Perfused Rat Liver Preparation

Selma Sahin and Malcolm Rowland
Drug Metabolism and Disposition March 1, 1999, 27 (3) 373-378;
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