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

Ulrik S. Justesen, Zoe Fox, Court Pedersen, Pedro Cahn, Jan Gerstoft, Nathan Clumeck, Marcello Losso, Barry Peters, Niels Obel, Antonella Castagna, Ulrik B. Dragsted, Jens D. Lundgren

Research output: Contribution to journalArticlepeer-review

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, Cmin, were obtained. Out of 656 randomized patients, 283 patients had available Cmin 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 Cmin within any treatment arm. A saquinavir Cmin > 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 Cmin from week 4 to week 48 in patients who remained on therapy. No association between treatment failure and the Cmin 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 Cmin several times above the minimum effective concentration.

Original languageEnglish
Pages (from-to)339-344
Number of pages6
JournalBasic and Clinical Pharmacology and Toxicology
Volume101
Issue number5
DOIs
Publication statusPublished - Nov 2007

ASJC Scopus subject areas

  • Pharmacology
  • Toxicology

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