Mechanisms of Pharmacokinetic Enhancement Between Ritonavir and Saquinavir; Micro/Small Dosing Tests Using Midazolam (CYP3A4), Fexofenadine (p-Glycoprotein), and Pravastatin (OATP1B1) as Probe Drugs

We investigated the mechanisms of ritonavir‐mediated enhancement effect on the pharmacokinetics of saquinavir using in vivo probes for CYP3A4 (midazolam), p‐glycoprotein (fexofenadine), and OATP1B1 (pravastatin) following oral micro/small dosing. A cocktail of the drugs (2 mg of saquinavir, 100 µg o...

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Published in:	Journal of clinical pharmacology Vol. 53; no. 6; pp. 654 - 661
Main Authors:	Ieiri, Ichiro, Tsunemitsu, Shyohei, Maeda, Kazuya, Ando, Yukie, Izumi, Noritomo, Kimura, Miyuki, Yamane, Naoe, Okuzono, Tsuyoshi, Morishita, Mariko, Kotani, Naoki, Kanda, Eri, Deguchi, Mariko, Matsuguma, Kyoko, Matsuki, Shunji, Hirota, Takeshi, Irie, Shin, Kusuhara, Hiroyuki, Sugiyama, Yuichi
Format:	Journal Article
Language:	English
Published:	England Blackwell Publishing Ltd 01-06-2013 American College of Clinical Pharmacology Wiley Subscription Services, Inc
Subjects:	Adult Area Under Curve ATP Binding Cassette Transporter, Subfamily B, Member 1 - antagonists & inhibitors ATP Binding Cassette Transporter, Subfamily B, Member 1 - metabolism boosting Chromatography, Liquid Cross-Over Studies Cytochrome P-450 CYP3A - metabolism Cytochrome P-450 CYP3A Inhibitors Dose-Response Relationship, Drug Drug Interactions fexofenadine HIV Protease Inhibitors - administration & dosage HIV Protease Inhibitors - pharmacokinetics HIV Protease Inhibitors - pharmacology Humans Intestines - drug effects Intestines - enzymology Liver - drug effects Liver - enzymology Liver-Specific Organic Anion Transporter 1 Male midazolam Midazolam - pharmacokinetics Organic Anion Transporters - drug effects Organic Anion Transporters - metabolism Pravastatin - pharmacokinetics ritonavir Ritonavir - administration & dosage Ritonavir - pharmacology saquinavir Saquinavir - pharmacokinetics Tandem Mass Spectrometry Terfenadine - analogs & derivatives Terfenadine - pharmacokinetics Young Adult
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