Document Detail

Saquinavir, nelfinavir and M8 pharmacokinetics following combined saquinavir, ritonavir and nelfinavir administration.
MedLine Citation:
PMID:  17255144     Owner:  NLM     Status:  MEDLINE    
OBJECTIVES: This study evaluated the steady-state pharmacokinetic interaction between ritonavir-boosted saquinavir and nelfinavir. METHODS: Open label, multiple-dose, two parallel-groups, single crossover study conducted in 24 HIV-infected patients (12 in each group). Patients in the nelfinavir group added saquinavir/ritonavir, 1000/100 mg twice daily to their ongoing stable treatment regimen consisting of nelfinavir, 1250 mg twice daily and two nucleoside reverse transcriptase inhibitors (NRTIs). Patients in the saquinavir group added nelfinavir, 1250 mg twice daily to their ongoing stable treatment regimen consisting of saquinavir/ritonavir, 1000/100 mg twice daily and two NRTIs. Pharmacokinetic assessments were performed before and 7 days after the start of combined treatment with nelfinavir/saquinavir/ritonavir. Blood samples were collected before and 1, 2, 3, 4, 6, 8, 10 and 12 h after dosing for measurement of nelfinavir, the nelfinavir metabolite M8 and saquinavir using liquid chromatography tandem mass spectrometry (LC-MS/MS). RESULTS: The addition of saquinavir/ritonavir to the nelfinavir-containing regimen resulted in significant increases in the M8 pharmacokinetic parameters AUC(0-12), Cmax and C12; geometric mean ratios (90% confidence intervals) of 2.25 ng.h/mL (1.47-3.44), 1.74 ng/mL (1.25-2.40) and 4.21 ng/mL (2.10-8.47), respectively. The intra-individual changes in nelfinavir and saquinavir concentrations were highly variable. Statistical analysis could not discard a relevant interaction but includes the possibility that some parameters may be halved, others more than doubled. At the same time the analysis failed to show any directed change. CONCLUSIONS: The co-administration of nelfinavir and saquinavir/ritonavir leads to unpredictable changes in concentrations of both drugs. It is unclear whether the increased concentrations of M8 are associated with a clinical benefit.
Hartmut Stocker; Christian Herzmann; Antje Breske; Guido Kruse; Marcel Berger; Hubert Schulbin; Andrew Hill; Jutta Steinmüller; Mark Becker; Keikawus Arastéh; Michael Kurowski
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Publication Detail:
Type:  Journal Article; Research Support, Non-U.S. Gov't     Date:  2007-01-25
Journal Detail:
Title:  The Journal of antimicrobial chemotherapy     Volume:  59     ISSN:  0305-7453     ISO Abbreviation:  J. Antimicrob. Chemother.     Publication Date:  2007 Mar 
Date Detail:
Created Date:  2007-02-27     Completed Date:  2007-05-11     Revised Date:  -    
Medline Journal Info:
Nlm Unique ID:  7513617     Medline TA:  J Antimicrob Chemother     Country:  England    
Other Details:
Languages:  eng     Pagination:  560-4     Citation Subset:  IM    
Vivantes Auguste-Viktoria Klinikum, Rubensstrasse 125, 12157 Berlin, Germany.
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MeSH Terms
Anti-HIV Agents / pharmacokinetics*
Cross-Over Studies
Drug Administration Schedule
Drug Interactions
Drug Therapy, Combination
HIV Infections / drug therapy*
Middle Aged
Nelfinavir / administration & dosage,  analogs & derivatives*,  pharmacokinetics*
Ritonavir / administration & dosage
Saquinavir / administration & dosage,  pharmacokinetics*
Reg. No./Substance:
0/Anti-HIV Agents; 0/Ritonavir; 0/hydroxy-t-butylamidenelfinavir; 127779-20-8/Saquinavir; 159989-64-7/Nelfinavir

From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine

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