Practical Perspectives on the Use of Tipranavir in Combination With Other Medications: Lessons Learned From Pharmacokinetic Studies

Boffito, Marta; Maitland, Desmond; Pozniak, Anton

doi:10.1177/0091270005283279

Cited by 16 publications

(5 citation statements)

References 23 publications

(66 reference statements)

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“…Thus, it is recommended that alternative or additional contraceptive measures are used when darunavir/r and the above oral contraceptives are combined. Ethinyl estradiol is metabolized by CYP3A and glucuronyl transferase; hence, this finding is consistent with other drugs (such as PIs) that affect these enzymes and lead to loss of ethinyl estradiol effectiveness [55,56].…”

Section: Oral Contraceptives/oestrogenssupporting

confidence: 80%

Darunavir: Pharmacokinetics and Drug Interactions

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Sekar²,

Hoetelmans

2008

Antiviral Therapy

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Darunavir (TMC114) is a new HIV protease inhibitor that has demonstrated substantial antiretroviral activity against wild-type HIV-1 virus and multidrug-resistant strains. Darunavir inhibits and is primarily metabolized by cytochrome P450 3A (CYP3A) isoenzymes and is coadministered with low-dose ritonavir (darunavir/r); ritonavir is an inhibitor of CYP3A isoenzymes and pharmacologically enhances darunavir, resulting in increased plasma concentrations and allowing for a lower daily dose. The t1/2 (terminal elimination half-life) of darunavir is 15 h in the presence of ritonavir. An extensive darunavir/r drug-drug interaction programme has been undertaken, covering a wide range of therapeutic areas. Studies conducted in HIV-negative healthy volunteers and in HIV-infected patients show that the potential for interactions is well characterized and the interactions are manageable. For most drugs investigated, no dose adjustments of darunavir/r or the co-administered drug are required. This article reviews all the pharmacokinetic and drug-drug interaction studies conducted to date for darunavir/r, providing guidance on how to co-administer darunavir/r with many other antiretroviral or non-antiretroviral medications commonly used in HIV-infected individuals.

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Section: Oral Contraceptives/oestrogenssupporting

confidence: 80%

Darunavir: Pharmacokinetics and Drug Interactions

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Sekar²,

Hoetelmans

2008

Antiviral Therapy

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“…It should be noted that protease inhibitors have different pharmacokinetic characteristics, giving them different competitive inhibitor profiles with regard to CYP3A substrates. For example, tipranavir combined with ritonavir has a weaker inhibition potential than agents such as lopinavir (Boffito et al, 2006;Abel et al, 2008). When administered alone, tipranavir induces CYP3A activity, whereas its coadministration with ritonavir results in CYP3A inhibition (MacGregor et al, 2004).…”

Section: E Cyp3a4/5mentioning

confidence: 99%

The Dual Role of Pharmacogenetics in HIV Treatment: Mutations and Polymorphisms Regulating Antiretroviral Drug Resistance and Disposition

et al. 2012

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“…PIs are not only substrates, but induce or inhibit cytochromes to a certain degree. The unwanted pharmacokinetic interactions between tipranavir, inducing CYP3A, and either saquinavir (SQV), lopinavir, or amprenavir led to the recommendation not to use these combinations in patients (4). Also, fosamprenavir and lopinavir-ritonavir (RTV) should not be used together, as the plasma concentrations of both PIs were significantly reduced when measured at steady state (23).…”

mentioning

confidence: 99%

Pharmacokinetics of Saquinavir, Atazanavir, and Ritonavir in a Twice-Daily Boosted Double-Protease Inhibitor Regimen

Hentig

Müller

Rottmann

et al. 2007

Antimicrob Agents Chemother

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The objective of this study was to evaluate the pharmacokinetics of atazanavir (ATV), saquinavir (SQV), and ritonavir (RTV) in a boosted double-protease inhibitor (PI) therapy regimen without reverse transcriptase inhibitors (RTIs). The study design was as follows. Patients with limited RTI options received a PI combination of 300/100 mg ATV/RTV once daily and 1,000 mg SQV twice daily (group 1; n ‫؍‬ 49) without RTI comedication. The results were compared to the plasma concentrations of PIs of patients taking either 300 mg ATV/100 mg RTV once daily plus RTIs (group 2; n ‫؍‬ 72) or patients taking 1,000 mg SQV/100 mg RTV plus RTIs (group 3; n ‫؍‬ 90). The study methods were as follows. Patients were given a 12/24-h pharmacokinetic assessment at steady state. Drug concentrations were measured by liquid chromatography-tandem mass spectrometry. The minimum and maximum concentrations (C min and C max ), area under the concentration-time curve under steady-state conditions (AUC ss ), elimination half-life, time of maximum concentration and lag time were subject to statistical analysis. The results show that patients treated with ATV/SQV/RTV exhibited significantly high SQV concentrations and moderate enhancement of the AUC ss of ATV in comparison to those of patients of the control groups: for SQV in groups 1 and 3, the geometric mean (GM) of the AUC ss was 22,794 versus 15,759 ng ⅐ h/ml (GM ratio [GMR] ‫؍‬ 1.45; P < 0.05), the GM of the C max was 3,257 versus 2,331 ng/ml (GMR ‫؍‬ 1.40; P < 0.05), and the GM of the C min was 438 versus 437 ng/ml (GMR ‫؍‬ 1.00); for ATV in groups 1 and 2, the GM of the AUC ss was 39,154 versus 33,626 ng ⅐ h/ml (GMR ‫؍‬ 1.16), the GM of the C max was 3,488 versus 2,924 ng/ml (GMR ‫؍‬ 1.20), and the GM of the C min was 515 versus 428 ng/ml (GMR ‫؍‬ 1.21). RTV levels were comparable for all groups. A subgroup analysis detected only marginal differences in ATV plasma exposure if combined with tenofovir-disoproxilfumarate and without it. We conclude that our pharmacokinetic results support the use of a boosted double-PI regimen of ATV/SQV/RTV as a treatment option for patients who need antiretroviral therapy without RTIs.

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Practical Perspectives on the Use of Tipranavir in Combination With Other Medications: Lessons Learned From Pharmacokinetic Studies

Cited by 16 publications

References 23 publications

Darunavir: Pharmacokinetics and Drug Interactions

Darunavir: Pharmacokinetics and Drug Interactions

The Dual Role of Pharmacogenetics in HIV Treatment: Mutations and Polymorphisms Regulating Antiretroviral Drug Resistance and Disposition

Pharmacokinetics of Saquinavir, Atazanavir, and Ritonavir in a Twice-Daily Boosted Double-Protease Inhibitor Regimen

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