Effect of serum lipids on the pharmacokinetics of atazanavir in hyperlipidemic rats.
Atazanavir (ATV) has been successfully used in HIV patients with severe hyperlipidemia (HL); however, little is known about the pharmacokinetics of ATV in HL. The aim of this study was to investigate the pharmacokinetics of ATV in HL. With the increase of serum lipids, the protein binding rate in HL rats (approximately 97%) was significantly higher than that in control (approximately 87%). After intravenous (iv), oral (po) and intraportal (ip) administration of ATV at a dosage of 7 mg/kg, AUCs in HL rats were 12.41, 5.24 and 8.89 microg/mLh, respectively, and were significantly higher than those in control rats (4.09, 1.70 and 3.38 microg/mLh). Despite the decrease of distribution volume (Vd(ss)), the terminal half-life (t(1/2)) in HL tended to be shorter than in control, and hepatic distribution of ATV in HL rats was 4.8-fold increases. These results suggested that the uptake of ATV into liver might counteract the decrease of Vd(ss). On the other hand, there was no significant difference in bioavailability, and the lymphatic transport to AUC showed no statistical change. In conclusion, although the protein binding rate and AUC were significantly increased, the pharmacokinetics of ATV might be tolerated in HL.
Fukushima
Keizo
K
Department of Pharmacokinetics, Kyoto Pharmaceutical University, Yamashina-ku, Kyoto, Japan. keizo@mb.kyoto-phu.ac.jp
Shibata
Masakazu
M
Mizuhara
Kazunori
K
Aoyama
Hiroaki
H
Uchisako
Rie
R
Kobuchi
Shinji
S
Sugioka
Nobuyuki
N
Takada
Kanji
K
D000818:Animals; D019380:Anti-HIV Agents / Q000493:pharmacokinetics*; D019540:Area Under Curve; D000069446:Atazanavir Sulfate; D006207:Half-Life; D006949:Hyperlipidemias / Q000378:metabolism*; D008297:Male; D009842:Oligopeptides / Q000493:pharmacokinetics*; D011485:Protein Binding; D011725:Pyridines / Q000493:pharmacokinetics*; D051381:Rats; D017208:Rats, Wistar
D019380:Anti-HIV Agents; D009842:Oligopeptides; D011725:Pyridines; D000069446:Atazanavir Sulfate