Atazanavir and lopinavir with ritonavir alone or in combination: analysis of pharmacokinetic interaction and predictors of drug exposure.

Simona Di Giambenedetto, Roberto Cauda, Pierluigi Navarra, Andrea De Luca, Alessandra Bacarelli, Enzo Ragazzoni, P. Villani, M. Regazzi

Risultato della ricerca: Contributo in rivistaArticolo in rivista

15 Citazioni (Scopus)


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 300 mg with ritonavir 100 mg q24h (group A) or lopinavir/ritonavir 400/100 mg q12h (group B) or atazanavir 300 mg q24h with lopinavir/ritonavir 400/100 mg 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 +/- 460 ng/mL, C(max) 3051 +/- 1996 ng/mL and AUC(24) 29 913 +/- 17 686 ng/mL/h. In group B (n=9), lopinavir C(min) was 7562 +/- 4292 ng/mL, C(max) 12 944 +/- 4838 ng/mL and AUC(0-12) 122 313 +/- 38 225 ng/mL/h. In group C (n=7), atazanavir C(min) was 876 +/- 460 ng/mL (P=0.039 vs. group A), C(max) 3421 +/- 3399 ng/mL and AUC(0-24) 65 055 +/- 49 843 ng/mL/h (two-sided P>0.05 for each comparison with group A), lopinavir C(min) was 7471 +/- 3745 ng/mL, C(max) 10 143 +/- 5217 ng/mL and AUC(0-12) 104 501 +/- 43 565 ng/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.
Lingua originaleEnglish
pagine (da-a)239-245
Numero di pagine7
RivistaHIV Medicine
Stato di pubblicazionePubblicato - 2008


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