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. 2005 Apr;49(4):1626-8.
doi: 10.1128/AAC.49.4.1626-1628.2005.

Role of P-glycoprotein in distribution of nelfinavir across the blood-mammary tissue barrier and blood-brain barrier

Jeffrey E Edwards  1 , Jane Alcorn, Juoko Savolainen, Bradley D Anderson, Patrick J McNamara
Affiliations

Role of P-glycoprotein in distribution of nelfinavir across the blood-mammary tissue barrier and blood-brain barrier

Jeffrey E Edwards et al. Antimicrob Agents Chemother. 2005 Apr.

Abstract

As a first approach in understanding the possible efficacy and toxicity of human immunodeficiency virus protease inhibitors during breast feeding, the milk-to-plasma ratio of nelfinavir was determined in lactating rats. The milk-to-plasma ratio of nelfinavir was determined to be 0.56 +/- 0.10 (means +/- standard deviations). Western blotting indicated that P-glycoprotein is expressed in rat mammary and brain tissue; however, the multidrug-resistant modulator GF120918 showed a significant effect only at the blood-brain barrier and not at the mammary-epithelial tissue barrier.

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Figures

FIG. 1.
FIG. 1.
P-gp expression in rat brain and mammary tissues. The expression of P-gp in rat brain (lanes 1 to 3) and mammary (lanes 4 to 6) tissue homogenates (40 μg of protein) was determined using Western blots with C219 (a) or JSB-1 (b) antibody.
FIG. 2.
FIG. 2.
Concentration-time profiles of nelfinavir in rat plasma (n = 6) and nelfinavr concentrations in milk (n = 6) and brain tissue (n = 3) at the 8-h time point in control animals (a) and GF120918-treated (10 mg · kg−1) animals (b). All values represent means ± SD.
FIG. 3.
FIG. 3.
Milk-to-plasma ratio of nelfinavir in the presence and absence of GF120918. All values represent means ± SD (n = 6 for each group).
FIG. 4.
FIG. 4.
Brain-to-plasma ratio of nelfinavir in the presence and absence of GF120918. All values represent means ± SD (n = 3 for each group).
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