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Antimicrobial Agents and Chemotherapy, July 1998, p. 1646-1653, Vol. 42, No. 7
0066-4804/98/$04.00+0
Copyright © 1998, American Society for Microbiology. All rights reserved.

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

Kishor M. Wasan,1,* Manisha Ramaswamy,1 Samson P. Ng,1 Wesley Wong,1 Steven C. Parrott,1 Joshua O. Ojwang,2 Thomas Wallace,3 and Paul A. Cossum3

Division of Pharmaceutics and Biopharmaceutics, Faculty of Pharmaceutical Sciences, The University of British Columbia, Vancouver, British Columbia, Canada1; ZymeTx, Inc., Oklahoma City, Oklahoma2; and Aronex Pharmaceuticals, Inc., The Woodlands, Texas3

Received 16 December 1997/Returned for modification 22 March 1998/Accepted 27 April 1998

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.

* Corresponding author. Mailing address: Division of Pharmaceutics and Biopharmaceutics, Faculty of Pharmaceutical Sciences, The University of British Columbia, Vancouver, British Columbia, Canada V6T 1Z3. Phone: (604) 822-4889. Fax: (604) 822-3035. E-mail: Kwasan{at}unixg.ubc.ca.

Antimicrobial Agents and Chemotherapy, July 1998, p. 1646-1653, Vol. 42, No. 7
0066-4804/98/$04.00+0
Copyright © 1998, American Society for Microbiology. All rights reserved.




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