Evaluation of steady-state pharmacokinetic interactions between ritonavir-boosted BILR 355, a non-nucleoside reverse transcriptase inhibitor, and lamivudine/zidovudine in healthy subjects

Huang, Fenglei; Allen, Lynn C.; Huang, David B.; Moy, F.; Vinisko, Richard; Nguyen, Thi My Linh; Rowland, Lois; MacGregor, Thomas R.; Castles, Mark; Robinson, Patrick

doi:10.1111/j.1365-2710.2010.01235.x

Cited by 4 publications

(3 citation statements)

References 33 publications

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“…Lopinavir and ritonavir decrease exposure to BILR 355 BS [117]. Similarly, concomitant administration of ritonavir-boosted BILR 355 BS with lamivudine/zidovudine [118] and emtricitabine/tenofovir disoproxil fumarate [119] led to a modest decrease in exposure to BILR 355 BS and an increase in exposure to other compounds.…”

Section: Next-generation Nnrtismentioning

confidence: 99%

Non‐nucleoside reverse transcriptase inhibitors: a review on pharmacokinetics, pharmacodynamics, safety and tolerability

Usach¹,

Melis²,

Peris³

2013

Journal of the International AIDS Society

235

241

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IntroductionHuman immunodeficiency virus (HIV) type-1 non-nucleoside and nucleoside reverse transcriptase inhibitors (NNRTIs) are key drugs of highly active antiretroviral therapy (HAART) in the clinical management of acquired immune deficiency syndrome (AIDS)/HIV infection.DiscussionFirst-generation NNRTIs, nevirapine (NVP), delavirdine (DLV) and efavirenz (EFV) are drugs with a low genetic barrier and poor resistance profile, which has led to the development of new generations of NNRTIs. Second-generation NNRTIs, etravirine (ETR) and rilpivirine (RPV) have been approved by the Food and Drug Administration and European Union, and the next generation of drugs is currently being clinically developed. This review describes recent clinical data, pharmacokinetics, metabolism, pharmacodynamics, safety and tolerability of commercialized NNRTIs, including the effects of sex, race and age differences on pharmacokinetics and safety. Moreover, it summarizes the characteristics of next-generation NNRTIs: lersivirine, GSK 2248761, RDEA806, BILR 355 BS, calanolide A, MK-4965, MK-1439 and MK-6186.ConclusionsThis review presents a wide description of NNRTIs, providing useful information for researchers interested in this field, both in clinical use and in research.

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Section: Next-generation Nnrtismentioning

confidence: 99%

Non‐nucleoside reverse transcriptase inhibitors: a review on pharmacokinetics, pharmacodynamics, safety and tolerability

Usach¹,

Melis²,

Peris³

2013

Journal of the International AIDS Society

235

241

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“… 14 – 17 However, the drug is <36% protein bound and with a half-life of 5–7 hours and rapid renal elimination is cataloged as a short-acting drug. 18 …”

Section: Introductionmentioning

confidence: 99%

Creation of a Long-Acting Nanoformulated 2′,3′-Dideoxy-3′-Thiacytidine

Guo

Zhou

Araínga

et al. 2017

JAIDS Journal of Acquired Immune Deficiency Syndromes

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“…Therefore, an important research focus is the development of new drugs that can be used in the treatment of HIV/AIDS [ 1 ] . The current international guidelines for the treatment of patients with an HIV infection recommend a regimen including 2 nucleoside reverse transcriptase inhibitors (NRTIs) plus a non-nucleoside reverse transcriptase inhibitor (NNRTI) or a protease inhibitors or an integrase strand transfer inhibitor [ 2 ] . 3-Cyanomethyl-4-methyl-DCK (CMDCK) is a promising anti-HIV agent belonging to a novel class of NNRTIs.…”

mentioning

confidence: 99%

Investigation of the Pharmacokinetic Interaction between Ritonavir and CMDCK, a New Non-nucleoside Reverse Transcriptase Inhibitor

Zhuang¹,

Shen²,

Yuan³

et al. 2013

Drug Res (Stuttg)

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The aim of this study was to investigate the pharmacokinetic interaction between ritonavir (RTV) and an anti-HIV agent 3-cyanomethyl-4-methyl-DCK (CMDCK). CMDCK was administered orally (8 mg/kg) and intravenously (2 mg/kg) to rats in the absence or presence of RTV (1 or 2.5 mg/kg). By comparing the pharmacokinetic parameters between the control and the RTV treated groups, it was found that co-administration with RTV could significantly increase the plasma exposure of CMDCK, through improving the hepatic and intestinal availabilities. The AUCinf of CMDCK was increased by 2.4 or 8.7 times for intravenous or oral route, respectively. The oral bioavailability of CMDCK was increased from 15% of the control group to 45% of the RTV concomitant group (2.5 mg/kg). In the in vitro studies with liver and intestinal microsomes, the K i values of RTV on the CMDCK metabolism were determined and found to be 0.22 and 0.48 µM for human, 0.33 and 1.60 µM for rat, respectively. Caco-2 cells study showed that CMDCK is not a P-glycoprotein (P-gp) substrate and its transepithelial transport is mainly through passive diffusion. The in vitro and in vivo results indicate that RTV could improve the bioavailability of CMDCK by inhibiting CYP3A mediated metabolism in both liver and intestine.

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Evaluation of steady-state pharmacokinetic interactions between ritonavir-boosted BILR 355, a non-nucleoside reverse transcriptase inhibitor, and lamivudine/zidovudine in healthy subjects

Abstract: Concomitant administration of BILR 355 with 3TC/ZDV resulted in a modest decrease in exposure to BILR 355 and a 45% increase in exposure to 3TC.

Cited by 4 publications

References 33 publications

Non‐nucleoside reverse transcriptase inhibitors: a review on pharmacokinetics, pharmacodynamics, safety and tolerability

Non‐nucleoside reverse transcriptase inhibitors: a review on pharmacokinetics, pharmacodynamics, safety and tolerability

Creation of a Long-Acting Nanoformulated 2′,3′-Dideoxy-3′-Thiacytidine

Investigation of the Pharmacokinetic Interaction between Ritonavir and CMDCK, a New Non-nucleoside Reverse Transcriptase Inhibitor

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