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Antimicrobial Agents and Chemotherapy, March 2001, p. 810-814, Vol. 45, No. 3
Department of
Medicine,1 National Jewish Center for Immunology
and Respiratory, Medicine, and Schools of
Pharmacy4 and
Medicine,5 University of
Colorado, Denver, Colorado, and Colleges of
Pharmacy2 and
Medicine,3 University of Arizona,
Tucson, Arizona
Received 20 March 2000/Returned for modification 11 October
2000/Accepted 7 December 2000
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 (AUC0-
0066-4804/01/$04.00+0 DOI: 10.1128/AAC.45.3.810-814.2001
Copyright © 2001, American Society for Microbiology. All rights reserved.
Pharmacokinetics of Ethionamide Administered under Fasting
Conditions or with Orange Juice, Food, or Antacids
) 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 AUC0- 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.
*
Corresponding author. Mailing address: Infectious
Disease Pharmacokinetics Laboratory, Room D-106, National Jewish
Medical and Research Center, 1400 Jackson St., Denver, CO 80206. Phone: (303) 398-1427. Fax: (303) 270-2229. E-mail:
peloquinc{at}njc.org.
Antimicrobial Agents and Chemotherapy, March 2001, p. 810-814, Vol. 45, No. 3
0066-4804/01/$04.00+0 DOI: 10.1128/AAC.45.3.810-814.2001
Copyright © 2001, American Society for Microbiology. All rights reserved.
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