Farmacokinetiek van de eenmaal-daagse combinatie raltegravir + atazanavir bij HIV-1-geïnfecteerde patiënten

Anita Jansen; E. P.H. Colbers; A. Van Der Ven; C. Richter; J. Rockstroh; Matthijs Van Luin; D. M. Burger

Farmacokinetiek van de eenmaal-daagse combinatie raltegravir + atazanavir bij HIV-1-geïnfecteerde patiënten

Translated title of the contribution: Pharmacokinetics of once-daily raltegravir + atazanavir in HIV-1 infected patients

Anita Jansen^*, E. P.H. Colbers, A. Van Der Ven, C. Richter, J. Rockstroh, Matthijs Van Luin, D. M. Burger

^*Corresponding author for this work

Research output: Contribution to journal › Article › Academic › peer-review

Abstract

OBJECTIVE: To compare the pharmacokinetics of raltegravir 400 mg twice daily vs. raltegravir 800 mg once daily in patients on unboosted atazanavir. Unboosted atazanavir increases plasma levels of raltegravir 400 mg twice daily by 72%, suggesting that combined use of atazanavir and raltegravir once daily is possible. Secondary objectives were to evaluate the safety and efficacy of this regimen. DESIGN: Open-label, multi-centre, phase-ll, multiple-dose study performed in two sequential periods of four weeks. METHODS: HIV-infected patients with undetectable viral load and no virological failure were eligible. In the first period patients received raltegravir 400 mg twice daily, atazanavir 600 mg once daily and either lamivudine 300 mg or emtricitabine 200 mg once daily. At week 2 a 24-hour pharmacokinetic curve, viral load and C_min of atazanavir were determined. If at week 2 viral load remained undetectable, C_min of atazanavir was > 0.12 mg/L, and the regimen was well tolerated, patients changed to once daily dosing. At week 6, a 24-hour pharmacokinetic curve, viral load and C_min of atazanavir were repeated. RESULTS: 18 patients 13 femates] were enrolled; 17 patients completed the study. The mean AUC_0-24h of raltegravir 800 mg once daily was 79% (CI90 24-157%) higher than the AUC_0-12h of 400 mg twice daily. The AUC_0-24h of 800 mg was not significantly different from two times the AUC_0-12h of 400 mg twice daily (P = 0.959). The C_max and C_min with raltegravir 800 mg once daily were 33% [CI90-11-97%] higher and 81% [CI90 58-91%] lower, respectively, than with 400 mg twice daily. Pharmacokinetic parameters of atazanavir were similar during both regimens. In all patients viral load remained undetectable and the regimen was well tolerated. CONCLUSION: A once daily regimen of raltegravir 800 mg in the presence of atazanavir 600 mg and lamivudine or emtricitabine results in AUC comparable to rattegravir 400 mg twice daily.

Translated title of the contribution	Pharmacokinetics of once-daily raltegravir + atazanavir in HIV-1 infected patients
Original language	Dutch
Pages (from-to)	180-184
Number of pages	5
Journal	Pharmaceutisch Weekblad
Volume	149
Issue number	43
Publication status	Published - 2014
Externally published	Yes

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@article{2b85b7703688406f962aeaa017472483,

title = "Farmacokinetiek van de eenmaal-daagse combinatie raltegravir + atazanavir bij HIV-1-ge{\"i}nfecteerde pati{\"e}nten",

abstract = "OBJECTIVE: To compare the pharmacokinetics of raltegravir 400 mg twice daily vs. raltegravir 800 mg once daily in patients on unboosted atazanavir. Unboosted atazanavir increases plasma levels of raltegravir 400 mg twice daily by 72%, suggesting that combined use of atazanavir and raltegravir once daily is possible. Secondary objectives were to evaluate the safety and efficacy of this regimen. DESIGN: Open-label, multi-centre, phase-ll, multiple-dose study performed in two sequential periods of four weeks. METHODS: HIV-infected patients with undetectable viral load and no virological failure were eligible. In the first period patients received raltegravir 400 mg twice daily, atazanavir 600 mg once daily and either lamivudine 300 mg or emtricitabine 200 mg once daily. At week 2 a 24-hour pharmacokinetic curve, viral load and Cmin of atazanavir were determined. If at week 2 viral load remained undetectable, Cmin of atazanavir was > 0.12 mg/L, and the regimen was well tolerated, patients changed to once daily dosing. At week 6, a 24-hour pharmacokinetic curve, viral load and Cmin of atazanavir were repeated. RESULTS: 18 patients 13 femates] were enrolled; 17 patients completed the study. The mean AUC0-24h of raltegravir 800 mg once daily was 79% (CI90 24-157%) higher than the AUC0-12h of 400 mg twice daily. The AUC0-24h of 800 mg was not significantly different from two times the AUC0-12h of 400 mg twice daily (P = 0.959). The Cmax and Cmin with raltegravir 800 mg once daily were 33% [CI90-11-97%] higher and 81% [CI90 58-91%] lower, respectively, than with 400 mg twice daily. Pharmacokinetic parameters of atazanavir were similar during both regimens. In all patients viral load remained undetectable and the regimen was well tolerated. CONCLUSION: A once daily regimen of raltegravir 800 mg in the presence of atazanavir 600 mg and lamivudine or emtricitabine results in AUC comparable to rattegravir 400 mg twice daily.",

author = "Anita Jansen and Colbers, {E. P.H.} and {Van Der Ven}, A. and C. Richter and J. Rockstroh and {Van Luin}, Matthijs and Burger, {D. M.}",

year = "2014",

language = "Dutch",

volume = "149",

pages = "180--184",

journal = "Pharmaceutisch Weekblad",

issn = "0031-6911",

publisher = "Kon. Ned. Mij. ter Bevordering der Pharmacie (KNMP)",

number = "43",

}

TY - JOUR

T1 - Farmacokinetiek van de eenmaal-daagse combinatie raltegravir + atazanavir bij HIV-1-geïnfecteerde patiënten

AU - Jansen, Anita

AU - Colbers, E. P.H.

AU - Van Der Ven, A.

AU - Richter, C.

AU - Rockstroh, J.

AU - Van Luin, Matthijs

AU - Burger, D. M.

PY - 2014

Y1 - 2014

N2 - OBJECTIVE: To compare the pharmacokinetics of raltegravir 400 mg twice daily vs. raltegravir 800 mg once daily in patients on unboosted atazanavir. Unboosted atazanavir increases plasma levels of raltegravir 400 mg twice daily by 72%, suggesting that combined use of atazanavir and raltegravir once daily is possible. Secondary objectives were to evaluate the safety and efficacy of this regimen. DESIGN: Open-label, multi-centre, phase-ll, multiple-dose study performed in two sequential periods of four weeks. METHODS: HIV-infected patients with undetectable viral load and no virological failure were eligible. In the first period patients received raltegravir 400 mg twice daily, atazanavir 600 mg once daily and either lamivudine 300 mg or emtricitabine 200 mg once daily. At week 2 a 24-hour pharmacokinetic curve, viral load and Cmin of atazanavir were determined. If at week 2 viral load remained undetectable, Cmin of atazanavir was > 0.12 mg/L, and the regimen was well tolerated, patients changed to once daily dosing. At week 6, a 24-hour pharmacokinetic curve, viral load and Cmin of atazanavir were repeated. RESULTS: 18 patients 13 femates] were enrolled; 17 patients completed the study. The mean AUC0-24h of raltegravir 800 mg once daily was 79% (CI90 24-157%) higher than the AUC0-12h of 400 mg twice daily. The AUC0-24h of 800 mg was not significantly different from two times the AUC0-12h of 400 mg twice daily (P = 0.959). The Cmax and Cmin with raltegravir 800 mg once daily were 33% [CI90-11-97%] higher and 81% [CI90 58-91%] lower, respectively, than with 400 mg twice daily. Pharmacokinetic parameters of atazanavir were similar during both regimens. In all patients viral load remained undetectable and the regimen was well tolerated. CONCLUSION: A once daily regimen of raltegravir 800 mg in the presence of atazanavir 600 mg and lamivudine or emtricitabine results in AUC comparable to rattegravir 400 mg twice daily.

AB - OBJECTIVE: To compare the pharmacokinetics of raltegravir 400 mg twice daily vs. raltegravir 800 mg once daily in patients on unboosted atazanavir. Unboosted atazanavir increases plasma levels of raltegravir 400 mg twice daily by 72%, suggesting that combined use of atazanavir and raltegravir once daily is possible. Secondary objectives were to evaluate the safety and efficacy of this regimen. DESIGN: Open-label, multi-centre, phase-ll, multiple-dose study performed in two sequential periods of four weeks. METHODS: HIV-infected patients with undetectable viral load and no virological failure were eligible. In the first period patients received raltegravir 400 mg twice daily, atazanavir 600 mg once daily and either lamivudine 300 mg or emtricitabine 200 mg once daily. At week 2 a 24-hour pharmacokinetic curve, viral load and Cmin of atazanavir were determined. If at week 2 viral load remained undetectable, Cmin of atazanavir was > 0.12 mg/L, and the regimen was well tolerated, patients changed to once daily dosing. At week 6, a 24-hour pharmacokinetic curve, viral load and Cmin of atazanavir were repeated. RESULTS: 18 patients 13 femates] were enrolled; 17 patients completed the study. The mean AUC0-24h of raltegravir 800 mg once daily was 79% (CI90 24-157%) higher than the AUC0-12h of 400 mg twice daily. The AUC0-24h of 800 mg was not significantly different from two times the AUC0-12h of 400 mg twice daily (P = 0.959). The Cmax and Cmin with raltegravir 800 mg once daily were 33% [CI90-11-97%] higher and 81% [CI90 58-91%] lower, respectively, than with 400 mg twice daily. Pharmacokinetic parameters of atazanavir were similar during both regimens. In all patients viral load remained undetectable and the regimen was well tolerated. CONCLUSION: A once daily regimen of raltegravir 800 mg in the presence of atazanavir 600 mg and lamivudine or emtricitabine results in AUC comparable to rattegravir 400 mg twice daily.

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M3 - Article

AN - SCOPUS:84949949501

SN - 0031-6911

VL - 149

SP - 180

EP - 184

JO - Pharmaceutisch Weekblad

JF - Pharmaceutisch Weekblad

IS - 43

ER -

Farmacokinetiek van de eenmaal-daagse combinatie raltegravir + atazanavir bij HIV-1-geïnfecteerde patiënten

Abstract

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