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Session 22 Oral Abstracts
Clinical Pharmacology: New Agents, Interactions, and Predictors of Virologic Response
Thursday, 10 am - 12:30 pm
Presentation Time: 10:30 am
Ballroom A


79
Steady-state Pharmacokinetics of Amprenavir, Lopinavir, and Efavirenz Combination in HIV-infected Patients
Paul Pham*1, P Barditch-Crovo1, E Redpath1, T Parson1, W Khan1, C Hendrix1, K Carson1, R Qaqish2, and C Flexner1
1Johns Hopkins Univ, Baltimore, MD, USA and 2Abbott Labs, Abbott Park, IL, USA

Background:  The combination of amprenavir (APV)/ lopinavir-ritonavir (LPV-r [Kaletra])/ efavirenz (EFV) with nucleoside analogues is a commonly used salvage regimen due to non-overlapping resistance profiles. Since these agents are substrates, inducers, and inhibitors of cytochrome P450 3A4, there are concerns for drug interactions affecting serum concentration of these antiretrovirals. We conducted an open-label study to determine the 4-way drug interaction of APV/LPV-r/EFV.

Methods:  HIV-infected patients who were receiving APV 750 twice daily + LPV/r 533 mg/133 mg twice daily without (n = 12) or with EFV 600 mg daily at bedtime (n = 7) underwent intensive pharmacokinetic analysis at steady-state. LPV and APV median Cmax, Tmax, Cmin, half-life, and AUC 0-12hr were compared between the 2 groups using the Mann-Whitney U-test.

 

Results:

PK Parameter

LPV (+APV)

Median (IQR range 25, 75)

LPV(+APV+EFV)

Median (IQR range 25 to 75)

p Value

Cmax (ng/mL)

11403 (10241, 13007)

10336 (8997, 10965)

0.272

Tmax (h)

5.16 (5.07, 6.11)

6.38 (3.03, 6.42)

0.611

Cmin (ng/mL)

4824 (3968, 6806)

5027 (1637, 6130)

0.447

AUC (ng·h/mL)

95101 (73281, 121068)

94244 (55061, 96414)

0.398

Half-life (h)

8.4 (5.18, 19.51)

5.72 (2.70, 9.54)

0.108

 

PK Parameter

APV (+LPV/r)

Median (IQR range 25 to 75)

APV (+LPV/r+ EFV)

Median (IQR range 25 to 75)

p Value

Cmax (ng/mL)

3768 (3215, 8063)

2468 (1781, 4721)

0.128

Tmax (h)

2.1 (1.23, 2.87)

2.4 (2.08, 3.03)

0.19

Cmin (ng/mL)

860 (606, 1712)

1053 (704, 1240)

0.735

AUC (ng·h/mL)

23129 (16290, 37173)

21145 (11878, 28370)

0.176

Half-life (h)

6.68 (5.01, 11.51)

7.61 (5.45, 11.49)

0.933

 

Conclusions:  At the studied dose of LPV-r 533 mg/133 mg twice daily + APV 750 mg twice daily, the pharmacokinetic profiles of LPV and APV were not significantly different in patients who also received EFV. LPV pharmacokinetic parameters were similar to historical controls receiving LPV-r 400 mg/100 mg twice daily. APV Cmin was similar to that seen with LPV 400 mg/100 mg twice daily + APV 600 or 750 mg twice daily or LPV/r 533 mg/133 mg twice daily + FPV 1400 mg twice daily.

 

Keywords: amprenavir; lopinavir; efavirenz