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Therapeutic drug monitoring of lopinavir/ritonavir given alone or with a non‐nucleoside reverse transcriptase inhibitor
Author(s) -
Solas Caroline,
PoizotMartin Isabelle,
Drogoul MariePierre,
Ravaux Isabelle,
Dhiver Catherine,
Lafeuillade Alain,
Allegre Thierry,
Mokhtari Malika,
Moreau Jacques,
Lepeu Gérard,
Petit Nathalie,
Durand Alain,
Lacarelle Bruno
Publication year - 2004
Publication title -
british journal of clinical pharmacology
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.216
H-Index - 146
eISSN - 1365-2125
pISSN - 0306-5251
DOI - 10.1046/j.1365-2125.2003.02020.x
Subject(s) - lopinavir , ritonavir , efavirenz , reverse transcriptase inhibitor , nevirapine , lopinavir/ritonavir , medicine , trough level , pharmacology , virology , human immunodeficiency virus (hiv) , viral load , tacrolimus , antiretroviral therapy , transplantation
Aims To evaluate the interindividual variability in the plasma concentrations of lopinavir in the context of routine monitoring with or without treatment with a non‐nucleoside reverse transcriptase inhibitor and to assess the interaction between the coformulation of lopinavir/ritonavir and efavirenz or nevirapine. Methods Plasma trough and peak concentrations ( C trough , C max ) of lopinavir from 182 HIV‐1‐infected patients were analysed by high‐performace liquid chromatography. Three lopinavir/ritonavir regimens were assessed, namely (A) 400 mg lopinavir/100 mg ritonavir twice daily given alone ( n = 125), (B) 400/100 mg twice daily together with a non‐nucleoside reverse transcriptase inhibitor ( n = 25), and (C) 533/133 mg twice daily together with a non‐nucleoside reverse transcriptase inhibitor ( n = 32). Results Median (ng ml −1 ) C trough and C max lopinavir (interquartile range, CV) were: (A) 4852 (3198–6891, 56%) and 8501 (6333–11 584, 41%), (B) 2979 (1704–5186, 74%) and 5612 (3362–11 704, 76%) and (C) 5082 (2696–7226, 74%) and 9757 (4883–12 963, 60%). Median C trough of lopinavir was lower in patients taking both efavirenz [ P = 0.01, 95% confidence interval (CI) for difference between medians 343, 2713] and nevirapine ( P = 0.019, 95% CI for difference between medians 354, 3681) compared with those taking lopinavir/ritonavir alone. A higher interindividual variability was observed when lopinavir/ritonavir was given with a non‐nucleoside reverse transcriptase inhibitor. The risk of achieving a ‘suboptimal’ C trough of lopinavir (below a threshold of 3000 ng ml −1 ) was statistically higher in patients treated with a non‐nucleoside reverse transcriptase inhibitor ( P < 0.001, 95% CI for difference between percentages 8.8, 43.1%) compared with those receiving lopinavir/ritonavir alone. Conclusions Our results confirmed the interaction between lopinavir and efavirenz, and also demonstrated a significant interaction between the former drug and nevirapine, resulting in lower C trough of lopinavir. The wide interpatient variability in this interaction suggests that therapeutic drug monitoring may be useful in optimizing the dose of lopinavir.