BACKGROUND: 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. METHODS: 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. RESULTS: Data from 439 patients on lopinavir (69% 400 mg/r, 31% 533 mg/r; 3% concomitant rifabutin) and 313 on atazanavir (60% 300 mg/r, 32% 400 mg/r, 8% 400 mg) were included. Multivariable models revealed the following predictors for lopinavir 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). CONCLUSIONS: 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.
BACKGROUND: The protease inhibitors lopinavir and atazanavir are both recommended for treatment of HIV-infectedpatients. 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. METHODS: 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. RESULTS: Data from 439 patients on lopinavir (69% 400 mg/r, 31% 533 mg/r; 3% concomitant rifabutin) and 313 on atazanavir (60% 300 mg/r, 32% 400 mg/r, 8% 400 mg) were included. Multivariable models revealed the following predictors for lopinavir 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). CONCLUSIONS: 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.
Authors: A L Pozniak; R F Miller; M C I Lipman; A R Freedman; L P Ormerod; M A Johnson; S Collins; S B Lucas Journal: HIV Med Date: 2005-07 Impact factor: 3.180
Authors: Alan Winston; Mark Bloch; Andrew Carr; Janaki Amin; Patrick W G Mallon; John Ray; Debbie Marriott; David A Cooper; Sean Emery Journal: J Antimicrob Chemother Date: 2005-07-04 Impact factor: 5.790
Authors: Ann Hsu; Jeffrey Isaacson; Scott Brun; Barry Bernstein; Wayne Lam; Richard Bertz; Cheryl Foit; Karen Rynkiewicz; Bruce Richards; Martin King; Richard Rode; Dale J Kempf; G Richard Granneman; Eugene Sun Journal: Antimicrob Agents Chemother Date: 2003-01 Impact factor: 5.191
Authors: Alessandro Schipani; Marco Siccardi; Antonio D'Avolio; Lorena Baietto; Marco Simiele; Stefano Bonora; Sonia Rodríguez Novoa; Lorena Cuenca; Vincent Soriano; Nitipatana Chierakul; Natpratou Saguenwong; Charoen Chuchuttaworn; Janelle M Hoskins; Anne M Dvorak; Howard L McLeod; Gerry Davies; Saye Khoo; David J Back; Giovanni Di Perri; Andrew Owen Journal: Antimicrob Agents Chemother Date: 2010-10-04 Impact factor: 5.191
Authors: Linhu Ye; Lei Cheng; Yan Deng; Hong Liu; Xinyu Wu; Tingting Wang; Qi Chang; Yan Zhang; Dan Wang; Zongze Li; Xixiao Yang Journal: Front Pharmacol Date: 2021-11-11 Impact factor: 5.810
Authors: Jean Claude Alvarez; Pierre Moine; Benjamin Davido; Isabelle Etting; Djillali Annane; Islam Amine Larabi; Nicolas Simon Journal: Eur J Clin Pharmacol Date: 2020-10-13 Impact factor: 2.953