Titre du document / Document title

Differences in the lipoprotein distribution of free and liposome-associated all-trans-retinoic acid in human, dog, and rat plasma are due to variations in lipoprotein lipid and protein content

Auteur(s) / Author(s)

WASAN K. M. ⁽¹⁾ ; RAMASWAMY M. ⁽¹⁾ ; NG S. P. ⁽¹⁾ ; WESLEY WONG ⁽¹⁾ ; PARROTT S. C. ⁽¹⁾ ; OJWANG J. O. ⁽²⁾ ; WALLACE T. ⁽³⁾ ; COSSUM P. A. ⁽³⁾ ;

Affiliation(s) du ou des auteurs / Author(s) Affiliation(s)

⁽¹⁾ Division of Pharmaceutics and Biopharmaceutics, Faculty of Pharmaceutical Sciences, The University of British Columbia, Vancouver, British Columbia, CANADA
⁽²⁾ ZymeTx, Inc., Oklahoma City, Oklahoma, ETATS-UNIS
⁽³⁾ Aronex Pharmaceuticals, Inc., The Woodlands, Texas, ETATS-UNIS

Résumé / Abstract

The objective of the proposed study was to determine the distribution in plasma lipoprotein of free all-trans retinoic acid (ATRA) and liposomal ATRA (Atragen; composed of dimyristoyl phosphatidylcholine and soybean oil) following incubation in human, rat, and dog plasma. When ATRA and Atragen at concentrations of 1, 5, 10, and 25 μg/ml were incubated in human and rat plasma for 5, 60, and 180 min, the majority of the tretinoin was recovered in the lipoprotein-deficient plasma fraction. However, when ATRA and Atragen were incubated in dog plasma, the majority of the tretinoin (>40%) was recovered in the high-density lipoprotein (HDL) fraction. No differences in the plasma distribution between ATRA and Atragen were found. These data suggest that a significant percentage of tretinoin associates with plasma lipoproteins (primarily the HDL fraction) upon incubation in human, dog, and rat plasma. Differences between the lipoprotein lipid and protein profiles in human plasma and in dog and rat plasma influenced the plasma distribution of ATRA and Atragen. Differences in lipoprotein distribution between ATRA and Atragen were not observed, suggesting that the drug's distribution in plasma is not influenced by its incorporation into these liposomes.

Revue / Journal Title

Antimicrobial agents and chemotherapy   ISSN 0066-4804   CODEN AACHAX 

Source / Source

1998, vol. 42, n^o7, pp. 1646-1653 (38 ref.)

Langue / Language

Anglais

Editeur / Publisher

American Society for Microbiology, Washington, DC, ETATS-UNIS  (1961) (Revue)

Mots-clés anglais / English Keywords

Retinoic acid ; Tretinoin ; Dosage form ; Lipoprotein ; Human ; Dog ; Rat ; Animal ; Blood plasma ; Distribution ; Liposome ; Antineoplastic agent ; Cholesterol ; Triglyceride ; Retinoids ; Lipids ; Protein content ; Fissipedia ; Carnivora ; Mammalia ; Vertebrata ; Rodentia ;

Mots-clés français / French Keywords

Rétinoïque acide ; Trétinoïne ; Forme pharmaceutique ; Lipoprotéine ; Homme ; Chien ; Rat ; Animal ; Plasma sanguin ; Distribution ; Liposome ; Anticancéreux ; Cholestérol ; Triglycéride ; Rétinoïde ; Lipide ; Teneur protéine ; Fissipedia ; Carnivora ; Mammalia ; Vertebrata ; Rodentia ;

Mots-clés espagnols / Spanish Keywords

Retinoico ácido ; Tretinoína ; Forma farmacéutica ; Lipoproteina ; Hombre ; Perro ; Rata ; Animal ; Plasma sanguíneo ; Distribución ; Liposoma ; Anticanceroso ; Colesterol ; Triglicérido ; Retinoide ; Lípido ; Contenido proteína ; Fissipedia ; Carnivora ; Mammalia ; Vertebrata ; Rodentia ;

Localisation / Location

INIST-CNRS, Cote INIST : 13334, 35400007709554.0210