TY - JOUR
T1 - Atazanavir and lopinavir with ritonavir alone or in combination
T2 - Analysis of pharmacokinetic interaction and predictors of drug exposure
AU - Di Giambenedetto, S.
AU - De Luca, A.
AU - Villani, P.
AU - Bacarelli, A.
AU - Ragazzoni, E.
AU - Regazzi, M.
AU - Cauda, R.
AU - Navarra, P.
PY - 2008/4
Y1 - 2008/4
N2 - Objectives: Studies on the pharmacokinetic interaction between atazanavir and lopinavir with ritonavir (lopinavir/ritonavir) report contradictory results. We aimed to establish the in vivo interaction between these two protease inhibitors as well as the variables influencing drug exposure. Methods: Pharmacokinetic parameters were investigated in HIV-infected patients treated with atazanavir 300mg with ritonavir 100mg q24h (group A) or lopinavir/ritonavir 400/100mg q12h (group B) or atazanavir 300mg q24h with lopinavir/ritonavir 400/100mg q12h (group C). Patients receiving other concomitant protease inhibitors or non-nucleoside reverse transcriptase inhibitors were excluded. Results: In group A (n=10), mean ± standard deviation atazanavir C min was 390 ± 460ng/mL, C max 3051 ± 1996ng/mL and AUC 24 29913 ± 17686ng/mL/h. In group B (n=9), lopinavir C min was 7562 ± 4292ng/mL, C max 12944 ± 4838ng/mL and AUC 0-12 122313 ± 38225ng/mL/h. In group C (n=7), atazanavir C min was 876 ± 460ng/mL (P=0.039 vs. group A), C max 3421 ± 3399ng/mL and AUC 0-24 65055 ± 49843ng/mL/h (two-sided P >0.05 for each comparison with group A), lopinavir C min was 7471 ± 3745ng/mL, C max 10143 ± 5217ng/mL and AUC 0-12 104501 ± 43565ng/mL/h (P >0.05 for each comparison with group B). When analysing all the groups, including controls from routine clinical practice, higher body mass index was associated with lower atazanavir C min and with lower lopinavir C max. Atazanavir C min showed a correlation with total bilirubin levels. Conclusions: Combination with lopinavir/ritonavir provides higher atazanavir C min than combination with ritonavir alone, possibly because of an effect of the additional ritonavir dose. Low BMI may be associated with higher drug exposure.
AB - Objectives: Studies on the pharmacokinetic interaction between atazanavir and lopinavir with ritonavir (lopinavir/ritonavir) report contradictory results. We aimed to establish the in vivo interaction between these two protease inhibitors as well as the variables influencing drug exposure. Methods: Pharmacokinetic parameters were investigated in HIV-infected patients treated with atazanavir 300mg with ritonavir 100mg q24h (group A) or lopinavir/ritonavir 400/100mg q12h (group B) or atazanavir 300mg q24h with lopinavir/ritonavir 400/100mg q12h (group C). Patients receiving other concomitant protease inhibitors or non-nucleoside reverse transcriptase inhibitors were excluded. Results: In group A (n=10), mean ± standard deviation atazanavir C min was 390 ± 460ng/mL, C max 3051 ± 1996ng/mL and AUC 24 29913 ± 17686ng/mL/h. In group B (n=9), lopinavir C min was 7562 ± 4292ng/mL, C max 12944 ± 4838ng/mL and AUC 0-12 122313 ± 38225ng/mL/h. In group C (n=7), atazanavir C min was 876 ± 460ng/mL (P=0.039 vs. group A), C max 3421 ± 3399ng/mL and AUC 0-24 65055 ± 49843ng/mL/h (two-sided P >0.05 for each comparison with group A), lopinavir C min was 7471 ± 3745ng/mL, C max 10143 ± 5217ng/mL and AUC 0-12 104501 ± 43565ng/mL/h (P >0.05 for each comparison with group B). When analysing all the groups, including controls from routine clinical practice, higher body mass index was associated with lower atazanavir C min and with lower lopinavir C max. Atazanavir C min showed a correlation with total bilirubin levels. Conclusions: Combination with lopinavir/ritonavir provides higher atazanavir C min than combination with ritonavir alone, possibly because of an effect of the additional ritonavir dose. Low BMI may be associated with higher drug exposure.
KW - Atazanavir
KW - Lopinavir/ritonavir
KW - Therapeutic drug monitoring
UR - http://www.scopus.com/inward/record.url?scp=41549144405&partnerID=8YFLogxK
UR - http://www.scopus.com/inward/citedby.url?scp=41549144405&partnerID=8YFLogxK
U2 - 10.1111/j.1468-1293.2008.00555.x
DO - 10.1111/j.1468-1293.2008.00555.x
M3 - Article
C2 - 18366448
AN - SCOPUS:41549144405
VL - 9
SP - 239
EP - 245
JO - HIV Medicine
JF - HIV Medicine
SN - 1464-2662
IS - 4
ER -