Intra-individual variability in efavirenz plasma concentrations supports therapeutic, drug monitoring based on quarterly sampling in the first year of therapy

Sofia A. Pereira, Teresa Branco, Umbelina Caixas, Rita M. Corte-Real, Isabel Germano, Fátima Lampreia, Emília C. Monteiro

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Abstract

Intrapatient variability in drug plasma concentrations is critical to the use of therapeutic drug monitoring with efavirenz, a non-nucleoside reverse-transcriptase inhibitor. Marked intrapatient variability, particularly for concentrations near the minimal therapeutic concentration, could be a predictor of virologic failure, meaning that a single concentration is of limited value. Previous reports on efavirenz; intra-individual variability were obtained only in follow-up periods of 3 to 12 months and do not provide a rationale for the periodicity of sample measurements needed in long-term therapy to identify patients with a large variability and increased risk of therapeutic failure. The aim of this work was to investigate intraindividual variability in efavirenz plasma concentrations over a long-term follow-up period to support therapeutic drug monitoring. In a case series study, clinical and laboratory data were collected from all HIV-positive adults at the immunodeficiency outpatient clinic who were on regimens containing efavirenz in 2002 and who gave their informed consent (n = 31). Efavirenz plasma concentrations were measured throughout a 3 year period, without dose adjustments. For each patient, 6 to 12 samples were obtained over the follow-up period with an interval of at least 3 months between each sample. Mean plasma concentrations (mg/L) in the first, second, and third year of follow-up were 2.20 +/- 0.64, 2.17 +/- 0.68, and 2.31 +/- 0.57. Mean intra-individual variability throughout the first, second, and third year of study was 27%, 31 %, and 25%, ranging from 12% to 63%. No differences in intrapatient variability in efavirenz plasma concentrations were found between. females and mates, HBV/HCV(+) and HBV/HCV(-) patients, or age above/below. 40 years. Mean values (intra-individual variability) in plasma concentrations (mg/L) found in 3 of 31 patients who experienced virologic failure were 1.78 (42%), 1.52 (16%), and 1.68 (45%). The high interindividual variability and low maintained values of intrapatient variability in plasma concentrations support therapeutic drug monitoring, which could be based on measurements taken quarterly during the first year of therapeutics. In patients presenting high values of intra-individual variability (eg, >40%) associated with low plasma concentrations (eg, <2 mg/L), more frequent measurements over longer periods (more than 1 yr) of controlled concentrations might be recommended, but this requires further investigation. Accession Number: WOS:000252877900010
Original languageEnglish
Pages (from-to)60-66
JournalTherapeutic Drug Monitoring
Volume30
Issue number1
DOIs
Publication statusPublished - Feb 2008

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efavirenz
Drug Monitoring
Therapeutics
Reverse Transcriptase Inhibitors
Periodicity
Ambulatory Care Facilities
Informed Consent

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@article{8b1a93ad17ae4f019fd0fdf9f8ea0599,
title = "Intra-individual variability in efavirenz plasma concentrations supports therapeutic, drug monitoring based on quarterly sampling in the first year of therapy",
abstract = "Intrapatient variability in drug plasma concentrations is critical to the use of therapeutic drug monitoring with efavirenz, a non-nucleoside reverse-transcriptase inhibitor. Marked intrapatient variability, particularly for concentrations near the minimal therapeutic concentration, could be a predictor of virologic failure, meaning that a single concentration is of limited value. Previous reports on efavirenz; intra-individual variability were obtained only in follow-up periods of 3 to 12 months and do not provide a rationale for the periodicity of sample measurements needed in long-term therapy to identify patients with a large variability and increased risk of therapeutic failure. The aim of this work was to investigate intraindividual variability in efavirenz plasma concentrations over a long-term follow-up period to support therapeutic drug monitoring. In a case series study, clinical and laboratory data were collected from all HIV-positive adults at the immunodeficiency outpatient clinic who were on regimens containing efavirenz in 2002 and who gave their informed consent (n = 31). Efavirenz plasma concentrations were measured throughout a 3 year period, without dose adjustments. For each patient, 6 to 12 samples were obtained over the follow-up period with an interval of at least 3 months between each sample. Mean plasma concentrations (mg/L) in the first, second, and third year of follow-up were 2.20 +/- 0.64, 2.17 +/- 0.68, and 2.31 +/- 0.57. Mean intra-individual variability throughout the first, second, and third year of study was 27{\%}, 31 {\%}, and 25{\%}, ranging from 12{\%} to 63{\%}. No differences in intrapatient variability in efavirenz plasma concentrations were found between. females and mates, HBV/HCV(+) and HBV/HCV(-) patients, or age above/below. 40 years. Mean values (intra-individual variability) in plasma concentrations (mg/L) found in 3 of 31 patients who experienced virologic failure were 1.78 (42{\%}), 1.52 (16{\%}), and 1.68 (45{\%}). The high interindividual variability and low maintained values of intrapatient variability in plasma concentrations support therapeutic drug monitoring, which could be based on measurements taken quarterly during the first year of therapeutics. In patients presenting high values of intra-individual variability (eg, >40{\%}) associated with low plasma concentrations (eg, <2 mg/L), more frequent measurements over longer periods (more than 1 yr) of controlled concentrations might be recommended, but this requires further investigation. Accession Number: WOS:000252877900010",
keywords = "INTRAPATIENT VARIABILITY, PHARMACOKINETICS, ANTIRETROVIRAL DRUGS, REVERSE-TRANSCRIPTASE INHIBITOR, HIV-1-INFECTED PATIENTS, TREATMENT FAILURE, INTERPATIENT, PERFORMANCE, HIV-INFECTED PATIENTS",
author = "Pereira, {Sofia A.} and Teresa Branco and Umbelina Caixas and Corte-Real, {Rita M.} and Isabel Germano and F{\'a}tima Lampreia and Monteiro, {Em{\'i}lia C.}",
year = "2008",
month = "2",
doi = "10.1097/FTD.0b013e318160ce76",
language = "English",
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publisher = "Lippincott Williams & Wilkins; 1999",
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TY - JOUR

T1 - Intra-individual variability in efavirenz plasma concentrations supports therapeutic, drug monitoring based on quarterly sampling in the first year of therapy

AU - Pereira, Sofia A.

AU - Branco, Teresa

AU - Caixas, Umbelina

AU - Corte-Real, Rita M.

AU - Germano, Isabel

AU - Lampreia, Fátima

AU - Monteiro, Emília C.

PY - 2008/2

Y1 - 2008/2

N2 - Intrapatient variability in drug plasma concentrations is critical to the use of therapeutic drug monitoring with efavirenz, a non-nucleoside reverse-transcriptase inhibitor. Marked intrapatient variability, particularly for concentrations near the minimal therapeutic concentration, could be a predictor of virologic failure, meaning that a single concentration is of limited value. Previous reports on efavirenz; intra-individual variability were obtained only in follow-up periods of 3 to 12 months and do not provide a rationale for the periodicity of sample measurements needed in long-term therapy to identify patients with a large variability and increased risk of therapeutic failure. The aim of this work was to investigate intraindividual variability in efavirenz plasma concentrations over a long-term follow-up period to support therapeutic drug monitoring. In a case series study, clinical and laboratory data were collected from all HIV-positive adults at the immunodeficiency outpatient clinic who were on regimens containing efavirenz in 2002 and who gave their informed consent (n = 31). Efavirenz plasma concentrations were measured throughout a 3 year period, without dose adjustments. For each patient, 6 to 12 samples were obtained over the follow-up period with an interval of at least 3 months between each sample. Mean plasma concentrations (mg/L) in the first, second, and third year of follow-up were 2.20 +/- 0.64, 2.17 +/- 0.68, and 2.31 +/- 0.57. Mean intra-individual variability throughout the first, second, and third year of study was 27%, 31 %, and 25%, ranging from 12% to 63%. No differences in intrapatient variability in efavirenz plasma concentrations were found between. females and mates, HBV/HCV(+) and HBV/HCV(-) patients, or age above/below. 40 years. Mean values (intra-individual variability) in plasma concentrations (mg/L) found in 3 of 31 patients who experienced virologic failure were 1.78 (42%), 1.52 (16%), and 1.68 (45%). The high interindividual variability and low maintained values of intrapatient variability in plasma concentrations support therapeutic drug monitoring, which could be based on measurements taken quarterly during the first year of therapeutics. In patients presenting high values of intra-individual variability (eg, >40%) associated with low plasma concentrations (eg, <2 mg/L), more frequent measurements over longer periods (more than 1 yr) of controlled concentrations might be recommended, but this requires further investigation. Accession Number: WOS:000252877900010

AB - Intrapatient variability in drug plasma concentrations is critical to the use of therapeutic drug monitoring with efavirenz, a non-nucleoside reverse-transcriptase inhibitor. Marked intrapatient variability, particularly for concentrations near the minimal therapeutic concentration, could be a predictor of virologic failure, meaning that a single concentration is of limited value. Previous reports on efavirenz; intra-individual variability were obtained only in follow-up periods of 3 to 12 months and do not provide a rationale for the periodicity of sample measurements needed in long-term therapy to identify patients with a large variability and increased risk of therapeutic failure. The aim of this work was to investigate intraindividual variability in efavirenz plasma concentrations over a long-term follow-up period to support therapeutic drug monitoring. In a case series study, clinical and laboratory data were collected from all HIV-positive adults at the immunodeficiency outpatient clinic who were on regimens containing efavirenz in 2002 and who gave their informed consent (n = 31). Efavirenz plasma concentrations were measured throughout a 3 year period, without dose adjustments. For each patient, 6 to 12 samples were obtained over the follow-up period with an interval of at least 3 months between each sample. Mean plasma concentrations (mg/L) in the first, second, and third year of follow-up were 2.20 +/- 0.64, 2.17 +/- 0.68, and 2.31 +/- 0.57. Mean intra-individual variability throughout the first, second, and third year of study was 27%, 31 %, and 25%, ranging from 12% to 63%. No differences in intrapatient variability in efavirenz plasma concentrations were found between. females and mates, HBV/HCV(+) and HBV/HCV(-) patients, or age above/below. 40 years. Mean values (intra-individual variability) in plasma concentrations (mg/L) found in 3 of 31 patients who experienced virologic failure were 1.78 (42%), 1.52 (16%), and 1.68 (45%). The high interindividual variability and low maintained values of intrapatient variability in plasma concentrations support therapeutic drug monitoring, which could be based on measurements taken quarterly during the first year of therapeutics. In patients presenting high values of intra-individual variability (eg, >40%) associated with low plasma concentrations (eg, <2 mg/L), more frequent measurements over longer periods (more than 1 yr) of controlled concentrations might be recommended, but this requires further investigation. Accession Number: WOS:000252877900010

KW - INTRAPATIENT VARIABILITY

KW - PHARMACOKINETICS

KW - ANTIRETROVIRAL DRUGS

KW - REVERSE-TRANSCRIPTASE INHIBITOR

KW - HIV-1-INFECTED PATIENTS

KW - TREATMENT FAILURE

KW - INTERPATIENT

KW - PERFORMANCE

KW - HIV-INFECTED PATIENTS

U2 - 10.1097/FTD.0b013e318160ce76

DO - 10.1097/FTD.0b013e318160ce76

M3 - Article

VL - 30

SP - 60

EP - 66

JO - Therapeutic Drug Monitoring

JF - Therapeutic Drug Monitoring

SN - 0163-4356

IS - 1

ER -