alexa Pharmacokinetic variability of antiretroviral drugs and correlation with virological outcome: 2 years of experience in routine clinical practice.
Pharmaceutical Sciences

Pharmaceutical Sciences

Journal of Pharmacogenomics & Pharmacoproteomics

Author(s): Fabbiani M, Di Giambenedetto S, Bracciale L, Bacarelli A, Ragazzoni E,

Abstract Share this page

Abstract OBJECTIVES: To assess the inter-individual and intra-individual plasma concentration variabilities of non-nucleoside reverse transcriptase inhibitors (NNRTIs) and protease inhibitors (PIs) in routine clinical practice and to investigate their relationships with virological failure. METHODS: We retrospectively enrolled HIV-infected patients undergoing therapeutic drug monitoring (TDM) of NNRTIs and PIs during routine outpatient visits. Plasma drug concentrations were measured by HPLC-UV and were considered therapeutic if above the proposed minimum efficacy trough concentration. Inter-individual and intra-individual variabilities were evaluated through the coefficient of variation (CV). RESULTS: A total of 457 PI and 172 NNRTI plasma concentrations were measured from 363 patients (HIV-RNA <50 copies/mL in 70.8\%, median CD4 count 434 cells/mm(3)). NNRTIs showed less inter-individual (CV(inter) 54.8\% versus 84.3\%) and intra-individual (CV(intra) 19.0\% versus 38.1\%) pharmacokinetic variabilities than PIs. Intra-individual variability was constantly lower than inter-individual variability for each drug. Subtherapeutic drug concentrations were observed in 106 samples (16.9\%). Older age (P = 0.020) and higher viral load (P = 0.013) were associated with subtherapeutic levels. Patients with therapeutic levels had a viral load of <50 copies/mL more frequently than those with subtherapeutic levels (74.8\% versus 63.2\%, P = 0.020). The estimated proportion with virological failure at 24 weeks was 0.21 in patients with suboptimal baseline drug levels and 0.08 in those with optimal levels (P < 0.001). In the multivariate analysis, therapeutic drug levels showed an independent negative association with virological failure (P = 0.004). CONCLUSIONS: A wide inter-individual and limited intra-individual pharmacokinetic variabilities, together with the demonstration of a concentration-response relationship, suggest that TDM is a useful tool for the clinical management of patients treated with NNRTIs or PIs. This article was published in J Antimicrob Chemother and referenced in Journal of Pharmacogenomics & Pharmacoproteomics

Relevant Expert PPTs

Relevant Speaker PPTs

Recommended Conferences

Relevant Topics

Peer Reviewed Journals
Make the best use of Scientific Research and information from our 700 + peer reviewed, Open Access Journals
International Conferences 2017-18
Meet Inspiring Speakers and Experts at our 3000+ Global Annual Meetings

Contact Us

© 2008-2017 OMICS International - Open Access Publisher. Best viewed in Mozilla Firefox | Google Chrome | Above IE 7.0 version