Pharmacokinetics of ethionamide administered under fasting conditions or with orange juice, food, or antacids

B. Auclair, David E. Nix, R. D. Adam, G. T. James, C. A. Peloquin

Research output: Contribution to journalArticle

39 Citations (Scopus)

Abstract

This study was conducted in order to (i) determine the effect of food, orange juice, or antacids on the absorption of a single oral 500-mg dose of ethionamide (ETA) in healthy volunteers, including an assessment of bioequivalence, and (ii) determine ETA population pharmacokinetic (PK) parameters. The pharmacokinetics of ETA in serum was determined for 12 healthy males and females in a randomized, four-period crossover study. Volunteers received single 500-mg doses of ETA either on an empty stomach (reference) or with food, orange juice, or antacids. Serum samples were collected for 48 h and assayed by high-performance liquid chromatography. Data were analyzed by noncompartmental and population methods. Mean test/reference ratios and 90% confidence intervals were determined. No statistically significant differences were seen in the maximum concentration of ETA (Cmax), time to maximum concentration (Tmax), or area under the concentration-time curve from 0 h to infinity (AUCo-∞) between the four treatments (P > 0.05 by analysis of variance). The least-squares mean ratios (with confidence intervals in parentheses) for Cmax were 105% (81.2 to 135%) after orange juice, 94% (72.8 to 121%) after food, and 88% (68.4 to 114%) after antacids. The least-squares mean ratios (with confidence intervals is in parentheses) for AUCo-∞ were 91% (72.7 to 115%) after orange juice, 96% (76.4 to 121%) after food, and 95% (75.5 to 120%) after antacids. The mean Tmax was slightly prolonged following antacid or food administration (2.3 to 2.6 h) compared to administration on an empty stomach or with juice (1.7 to 1.9 h). The median population PK parameters were as follows: Ka = 0.37 to 0.48 h-1, V/F = 2.0 to 2.8 liters/kg, CL/F = 56.5 to 72.2 liters/h, and terminal half-life = 1.7 to 2.1 h, where Ka is the absorption rate constant, V is the volume of distribution, and CL is clearance. The PK behavior of ETA was not significantly modified by the different conditions studied. Mean ratios for AUC ranged from 0.91 to 0.96 for the orange juice, food, and antacid treatments, indicating a minimal effect on relative bioavailability. ETA can, therefore, be administered with food if tolerance is an issue.

Original languageEnglish (US)
Pages (from-to)810-814
Number of pages5
JournalAntimicrobial Agents and Chemotherapy
Volume45
Issue number3
DOIs
StatePublished - 2001
Externally publishedYes

Fingerprint

Ethionamide
Antacids
Fasting
Pharmacokinetics
Food
Confidence Intervals
Least-Squares Analysis
Stomach
Population
Therapeutic Equivalency
Serum
Cross-Over Studies
Biological Availability
Area Under Curve
Half-Life
Volunteers
Analysis of Variance
Healthy Volunteers
High Pressure Liquid Chromatography

ASJC Scopus subject areas

  • Pharmacology (medical)

Cite this

Pharmacokinetics of ethionamide administered under fasting conditions or with orange juice, food, or antacids. / Auclair, B.; Nix, David E.; Adam, R. D.; James, G. T.; Peloquin, C. A.

In: Antimicrobial Agents and Chemotherapy, Vol. 45, No. 3, 2001, p. 810-814.

Research output: Contribution to journalArticle

@article{2b9377459f894c179693cfd4fa38f6a5,
title = "Pharmacokinetics of ethionamide administered under fasting conditions or with orange juice, food, or antacids",
abstract = "This study was conducted in order to (i) determine the effect of food, orange juice, or antacids on the absorption of a single oral 500-mg dose of ethionamide (ETA) in healthy volunteers, including an assessment of bioequivalence, and (ii) determine ETA population pharmacokinetic (PK) parameters. The pharmacokinetics of ETA in serum was determined for 12 healthy males and females in a randomized, four-period crossover study. Volunteers received single 500-mg doses of ETA either on an empty stomach (reference) or with food, orange juice, or antacids. Serum samples were collected for 48 h and assayed by high-performance liquid chromatography. Data were analyzed by noncompartmental and population methods. Mean test/reference ratios and 90{\%} confidence intervals were determined. No statistically significant differences were seen in the maximum concentration of ETA (Cmax), time to maximum concentration (Tmax), or area under the concentration-time curve from 0 h to infinity (AUCo-∞) between the four treatments (P > 0.05 by analysis of variance). The least-squares mean ratios (with confidence intervals in parentheses) for Cmax were 105{\%} (81.2 to 135{\%}) after orange juice, 94{\%} (72.8 to 121{\%}) after food, and 88{\%} (68.4 to 114{\%}) after antacids. The least-squares mean ratios (with confidence intervals is in parentheses) for AUCo-∞ were 91{\%} (72.7 to 115{\%}) after orange juice, 96{\%} (76.4 to 121{\%}) after food, and 95{\%} (75.5 to 120{\%}) after antacids. The mean Tmax was slightly prolonged following antacid or food administration (2.3 to 2.6 h) compared to administration on an empty stomach or with juice (1.7 to 1.9 h). The median population PK parameters were as follows: Ka = 0.37 to 0.48 h-1, V/F = 2.0 to 2.8 liters/kg, CL/F = 56.5 to 72.2 liters/h, and terminal half-life = 1.7 to 2.1 h, where Ka is the absorption rate constant, V is the volume of distribution, and CL is clearance. The PK behavior of ETA was not significantly modified by the different conditions studied. Mean ratios for AUC ranged from 0.91 to 0.96 for the orange juice, food, and antacid treatments, indicating a minimal effect on relative bioavailability. ETA can, therefore, be administered with food if tolerance is an issue.",
author = "B. Auclair and Nix, {David E.} and Adam, {R. D.} and James, {G. T.} and Peloquin, {C. A.}",
year = "2001",
doi = "10.1128/AAC.45.3.810-814.2001",
language = "English (US)",
volume = "45",
pages = "810--814",
journal = "Antimicrobial Agents and Chemotherapy",
issn = "0066-4804",
publisher = "American Society for Microbiology",
number = "3",

}

TY - JOUR

T1 - Pharmacokinetics of ethionamide administered under fasting conditions or with orange juice, food, or antacids

AU - Auclair, B.

AU - Nix, David E.

AU - Adam, R. D.

AU - James, G. T.

AU - Peloquin, C. A.

PY - 2001

Y1 - 2001

N2 - This study was conducted in order to (i) determine the effect of food, orange juice, or antacids on the absorption of a single oral 500-mg dose of ethionamide (ETA) in healthy volunteers, including an assessment of bioequivalence, and (ii) determine ETA population pharmacokinetic (PK) parameters. The pharmacokinetics of ETA in serum was determined for 12 healthy males and females in a randomized, four-period crossover study. Volunteers received single 500-mg doses of ETA either on an empty stomach (reference) or with food, orange juice, or antacids. Serum samples were collected for 48 h and assayed by high-performance liquid chromatography. Data were analyzed by noncompartmental and population methods. Mean test/reference ratios and 90% confidence intervals were determined. No statistically significant differences were seen in the maximum concentration of ETA (Cmax), time to maximum concentration (Tmax), or area under the concentration-time curve from 0 h to infinity (AUCo-∞) between the four treatments (P > 0.05 by analysis of variance). The least-squares mean ratios (with confidence intervals in parentheses) for Cmax were 105% (81.2 to 135%) after orange juice, 94% (72.8 to 121%) after food, and 88% (68.4 to 114%) after antacids. The least-squares mean ratios (with confidence intervals is in parentheses) for AUCo-∞ were 91% (72.7 to 115%) after orange juice, 96% (76.4 to 121%) after food, and 95% (75.5 to 120%) after antacids. The mean Tmax was slightly prolonged following antacid or food administration (2.3 to 2.6 h) compared to administration on an empty stomach or with juice (1.7 to 1.9 h). The median population PK parameters were as follows: Ka = 0.37 to 0.48 h-1, V/F = 2.0 to 2.8 liters/kg, CL/F = 56.5 to 72.2 liters/h, and terminal half-life = 1.7 to 2.1 h, where Ka is the absorption rate constant, V is the volume of distribution, and CL is clearance. The PK behavior of ETA was not significantly modified by the different conditions studied. Mean ratios for AUC ranged from 0.91 to 0.96 for the orange juice, food, and antacid treatments, indicating a minimal effect on relative bioavailability. ETA can, therefore, be administered with food if tolerance is an issue.

AB - This study was conducted in order to (i) determine the effect of food, orange juice, or antacids on the absorption of a single oral 500-mg dose of ethionamide (ETA) in healthy volunteers, including an assessment of bioequivalence, and (ii) determine ETA population pharmacokinetic (PK) parameters. The pharmacokinetics of ETA in serum was determined for 12 healthy males and females in a randomized, four-period crossover study. Volunteers received single 500-mg doses of ETA either on an empty stomach (reference) or with food, orange juice, or antacids. Serum samples were collected for 48 h and assayed by high-performance liquid chromatography. Data were analyzed by noncompartmental and population methods. Mean test/reference ratios and 90% confidence intervals were determined. No statistically significant differences were seen in the maximum concentration of ETA (Cmax), time to maximum concentration (Tmax), or area under the concentration-time curve from 0 h to infinity (AUCo-∞) between the four treatments (P > 0.05 by analysis of variance). The least-squares mean ratios (with confidence intervals in parentheses) for Cmax were 105% (81.2 to 135%) after orange juice, 94% (72.8 to 121%) after food, and 88% (68.4 to 114%) after antacids. The least-squares mean ratios (with confidence intervals is in parentheses) for AUCo-∞ were 91% (72.7 to 115%) after orange juice, 96% (76.4 to 121%) after food, and 95% (75.5 to 120%) after antacids. The mean Tmax was slightly prolonged following antacid or food administration (2.3 to 2.6 h) compared to administration on an empty stomach or with juice (1.7 to 1.9 h). The median population PK parameters were as follows: Ka = 0.37 to 0.48 h-1, V/F = 2.0 to 2.8 liters/kg, CL/F = 56.5 to 72.2 liters/h, and terminal half-life = 1.7 to 2.1 h, where Ka is the absorption rate constant, V is the volume of distribution, and CL is clearance. The PK behavior of ETA was not significantly modified by the different conditions studied. Mean ratios for AUC ranged from 0.91 to 0.96 for the orange juice, food, and antacid treatments, indicating a minimal effect on relative bioavailability. ETA can, therefore, be administered with food if tolerance is an issue.

UR - http://www.scopus.com/inward/record.url?scp=0035115721&partnerID=8YFLogxK

UR - http://www.scopus.com/inward/citedby.url?scp=0035115721&partnerID=8YFLogxK

U2 - 10.1128/AAC.45.3.810-814.2001

DO - 10.1128/AAC.45.3.810-814.2001

M3 - Article

C2 - 11181366

AN - SCOPUS:0035115721

VL - 45

SP - 810

EP - 814

JO - Antimicrobial Agents and Chemotherapy

JF - Antimicrobial Agents and Chemotherapy

SN - 0066-4804

IS - 3

ER -