Our objective was to identify possible differences in protease inhibitor plasma concentrations between and within three protease inhibitor regimens (indinavir, saquinavir and lopinavir all in combination with low-dose ritonavir) and to relate these differences to safety and efficacy. Data originated from pre-defined pharmacokinetic substudies within two randomized 48-week trials evaluating the safety and efficacy of three protease inhibitor regimens. At weeks 4 and 48, plasma was collected and minimum drug plasma concentrations, C-min, were obtained. Out of 656 randomized patients, 283 patients had available C-min at week 4. Indinavir, saquinavir and lopinavir C-min were high when combined with low-dose ritonavir. No significant difference in the proportion of patients experiencing treatment failure could be found according to the C-min within any treatment arm. A saquinavir C-min > 2000 ng/ml was associated with an increased risk of gastrointestinal grade 3 or 4 adverse events and higher total cholesterol. Overall, there were no changes in C-min from week 4 to week 48 in patients who remained on therapy. No association between treatment failure and the C-min could be demonstrated. Associations between high C-min and toxicity were identified in the saquinavir arm; therefore, dose reductions may be appropriate in certain patients with C-min several times above the minimum effective concentration.
Pharmacokinetics of two randomized trials evaluating the safety and efficacy of indinavir, saquinavir and lopinavir in combination with low-dose ritonavir: The MaxCmin1 and 2 trials
CASTAGNA , ANTONELLA;
2007-01-01
Abstract
Our objective was to identify possible differences in protease inhibitor plasma concentrations between and within three protease inhibitor regimens (indinavir, saquinavir and lopinavir all in combination with low-dose ritonavir) and to relate these differences to safety and efficacy. Data originated from pre-defined pharmacokinetic substudies within two randomized 48-week trials evaluating the safety and efficacy of three protease inhibitor regimens. At weeks 4 and 48, plasma was collected and minimum drug plasma concentrations, C-min, were obtained. Out of 656 randomized patients, 283 patients had available C-min at week 4. Indinavir, saquinavir and lopinavir C-min were high when combined with low-dose ritonavir. No significant difference in the proportion of patients experiencing treatment failure could be found according to the C-min within any treatment arm. A saquinavir C-min > 2000 ng/ml was associated with an increased risk of gastrointestinal grade 3 or 4 adverse events and higher total cholesterol. Overall, there were no changes in C-min from week 4 to week 48 in patients who remained on therapy. No association between treatment failure and the C-min could be demonstrated. Associations between high C-min and toxicity were identified in the saquinavir arm; therefore, dose reductions may be appropriate in certain patients with C-min several times above the minimum effective concentration.I documenti in IRIS sono protetti da copyright e tutti i diritti sono riservati, salvo diversa indicazione.
