Factors influencing lopinavir and atazanavir plasma concentration

By:

Stohr, W

Contributor(s):

Publication details: 2010ISSN:

03057453

Uniform titles:

Journal of Antimicrobial Chemotherapy

Online resources:

Summary: <div style="line-height: 17.999801635742188px;"><h4 style="margin: 0px 0.25em 0px 0px; text-transform: uppercase; float: left;">BACKGROUND:</h4>The protease inhibitors lopinavir and atazanavir are both recommended for treatment of HIV-infected patients. Considerable inter-individual variability in plasma concentration has been observed for both drugs. The aim of this study was to evaluate which demographic factors and concomitant drugs are associated with lopinavir and atazanavir plasma concentration.<h4 style="margin: 0px 0.25em 0px 0px; text-transform: uppercase; float: left;">METHODS:</h4>Data from the Liverpool TDM (therapeutic drug monitoring) Registry were linked with the UK Collaborative HIV Cohort (CHIC) study. For each patient, the first measurement of lopinavir (twice daily) or atazanavir [once daily, ritonavir boosted (/r) or unboosted] plasma concentration was included. Linear regression was used to evaluate the association of dose, gender, age, weight, ethnicity and concomitant antiretroviral drugs or rifabutin with log-transformed drug concentration, adjusted for time since last intake.<h4 style="margin: 0px 0.25em 0px 0px; text-transform: uppercase; float: left;">RESULTS:</h4>Data from 439 patients on lopinavir (69% 400 mg/r, 31% 533 mg/r; 3% concomitant rifabutin) and 313 onatazanavir (60% 300 mg/r, 32% 400 mg/r, 8% 400 mg) were included. Multivariable models revealed the following predictors forlopinavir concentration: weight (11% decrease per additional 10 kg; P = 0.001); dose (25% increase for 533 mg/r; P = 0.024); and rifabutin (116% increase; P < 0.001). For atazanavir the predictors were dose (compared with 300 mg/r: 40% increase for 400 mg/r, 67% decrease for 400 mg; overall P < 0.001) and efavirenz (32% decrease; P = 0.016) but not tenofovir (P = 0.54).<h4 style="margin: 0px 0.25em 0px 0px; text-transform: uppercase; float: left;">CONCLUSIONS:</h4>This analysis confirms that efavirenz decreases atazanavir concentrations, and there was a negative association of weight and lopinavir concentrations. The strong impact of rifabutin on lopinavir concentration should be studied further.</div>

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Item type	Home library	Collection	Class number	Status	Date due	Barcode
Book	Ferriman information and Library Service (North Middlesex) Shelves	Staff publications for NMDX		Available

NMUH Staff Publications

<div style="line-height: 17.999801635742188px;"><h4 style="margin: 0px 0.25em 0px 0px; text-transform: uppercase; float: left;">BACKGROUND:</h4>The protease inhibitors&nbsp;lopinavir&nbsp;and&nbsp;atazanavir&nbsp;are both recommended for treatment of HIV-infected patients. Considerable inter-individual variability in&nbsp;plasma&nbsp;concentration&nbsp;has been observed for both drugs. The aim of this study was to evaluate which demographic&nbsp;factors&nbsp;and concomitant drugs are associated with&nbsp;lopinavir&nbsp;and&nbsp;atazanavir&nbsp;plasma&nbsp;concentration.<h4 style="margin: 0px 0.25em 0px 0px; text-transform: uppercase; float: left;">METHODS:</h4>Data from the Liverpool TDM (therapeutic drug monitoring) Registry were linked with the UK Collaborative HIV Cohort (CHIC) study. For each patient, the first measurement of&nbsp;lopinavir&nbsp;(twice daily) or&nbsp;atazanavir&nbsp;[once daily, ritonavir boosted (/r) or unboosted]&nbsp;plasma&nbsp;concentration&nbsp;was included. Linear regression was used to evaluate the association of dose, gender, age, weight, ethnicity and concomitant antiretroviral drugs or rifabutin with log-transformed drug&nbsp;concentration, adjusted for time since last intake.<h4 style="margin: 0px 0.25em 0px 0px; text-transform: uppercase; float: left;">RESULTS:</h4>Data from 439 patients on&nbsp;lopinavir&nbsp;(69% 400 mg/r, 31% 533 mg/r; 3% concomitant rifabutin) and 313 onatazanavir&nbsp;(60% 300 mg/r, 32% 400 mg/r, 8% 400 mg) were included. Multivariable models revealed the following predictors forlopinavir&nbsp;concentration: weight (11% decrease per additional 10 kg; P = 0.001); dose (25% increase for 533 mg/r; P = 0.024); and rifabutin (116% increase; P &lt; 0.001). For&nbsp;atazanavir&nbsp;the predictors were dose (compared with 300 mg/r: 40% increase for 400 mg/r, 67% decrease for 400 mg; overall P &lt; 0.001) and efavirenz (32% decrease; P = 0.016) but not tenofovir (P = 0.54).<h4 style="margin: 0px 0.25em 0px 0px; text-transform: uppercase; float: left;">CONCLUSIONS:</h4>This analysis confirms that efavirenz decreases&nbsp;atazanavir&nbsp;concentrations, and there was a negative association of weight and&nbsp;lopinavir&nbsp;concentrations. The strong impact of rifabutin on&nbsp;lopinavir&nbsp;concentration&nbsp;should be studied further.</div>

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