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 journalArticle

7 Citations (Scopus)

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

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Saquinavir
Lopinavir
Indinavir
Ritonavir
Pharmacokinetics
Protease Inhibitors
Safety
Plasmas
Treatment Failure
Patient treatment
Toxicity
Cholesterol
Association reactions
Pharmaceutical Preparations
Therapeutics

ASJC Scopus subject areas

  • Pharmacology
  • Toxicology

Cite this

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

In: Basic and Clinical Pharmacology and Toxicology, Vol. 101, No. 5, 11.2007, p. 339-344.

Research output: Contribution to journalArticle

Justesen, Ulrik S. ; Fox, Zoe ; Pedersen, Court ; Cahn, Pedro ; Gerstoft, Jan ; Clumeck, Nathan ; Losso, Marcello ; Peters, Barry ; Obel, Niels ; Castagna, Antonella ; Dragsted, Ulrik B. ; Lundgren, Jens D. / 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. In: Basic and Clinical Pharmacology and Toxicology. 2007 ; Vol. 101, No. 5. pp. 339-344.
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