Role of P-glycoprotein in distribution of nelfinavir across the blood-mammary tissue barrier and blood-brain barrier.
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.
Edwards
Jeffrey E
JE
Environmental and Molecular Toxicology, North Carolina State University, Raleigh, North Carolina, USA.
Alcorn
Jane
J
Savolainen
Juoko
J
Anderson
Bradley D
BD
McNamara
Patrick J
PJ
D020168:ATP Binding Cassette Transporter, Subfamily B, Member 1 / Q000378:metabolism*; D000166:Acridines / Q000494:pharmacology; D000818:Animals; D000831:Animals, Newborn; D001812:Blood-Brain Barrier / Q000378:metabolism*; D005260:Female; D017320:HIV Protease Inhibitors / Q000097:blood / Q000493:pharmacokinetics*; D007774:Lactation; D008321:Mammary Glands, Animal / Q000378:metabolism*; D008892:Milk / Q000378:metabolism; D019888:Nelfinavir / Q000097:blood / Q000493:pharmacokinetics*; D051381:Rats; D017207:Rats, Sprague-Dawley; D044005:Tetrahydroisoquinolines / Q000494:pharmacology
D020168:ATP Binding Cassette Transporter, Subfamily B, Member 1; D000166:Acridines; D017320:HIV Protease Inhibitors; D044005:Tetrahydroisoquinolines; D019888:Nelfinavir; C083501:Elacridar