Pharmacokinetics of isoniazid under fasting conditions, with food, and with antacids

Charles A. Peloquin, R. Namdar, A. A. Dodge, David E. Nix

Research output: Contribution to journalArticle

79 Citations (Scopus)

Abstract

STUDY OBJECTIVES: To determine the intra- and intersubject variability in and the effects of food or antacids on the pharmacokinetics of isoniazid (INH). DESIGN: Randomized, four-period cross-over Phase I study in 14 healthy male and female volunteers. Subjects ingested single doses of INH 300 mg under fasting conditions twice, with a high-fat meal, and with aluminum- magnesium antacid. They also received standard doses of rifampin, pyrazinamide, and ethambutol. RESULTS: Serum was collected for 48 hours, and assayed by high performance liquid chromatography (HPLC). Data were analyzed using noncompartmental methods and a compartmental analysis using nonparametric expectation maximization. Both fasting conditions produced similar results: a mean INH C(max) of 5.53 ± 2.92 μg/ml, T(max) of 1.02 ± 1.10 hours, and AUC(0-∞) of 20.16 ± 12.45 μg* hr/ml. These findings are similar to those reported previously. Antacids did not alter these parameters significantly (C(max) of 5.62 ± 2.53 μg/ml, T(max) of 0.71 ± 0.56 hours, and AUC(0-∞) of 20.27 ± 11.39 μg* hr/ml). In contrast, the high-fat meal recommended by the Food and Drug Administration reduced INH C(max) by 51% (2.73 ± 1.70 μg/ml), nearly doubled T(max) (1.93 ± 1.61 hours), and reduced AUC(0-∞) by 12% (17.72 ± 10.32 μg*hr/ml). CONCLUSIONS: These changes in C(max), T(max), and AUC(0-∞) can be avoided by giving INH on an empty stomach whenever possible.

Original languageEnglish (US)
Pages (from-to)703-710
Number of pages8
JournalInternational Journal of Tuberculosis and Lung Disease
Volume3
Issue number8
StatePublished - Aug 1999

Fingerprint

Antacids
Isoniazid
Area Under Curve
Fasting
Pharmacokinetics
Food
Meals
Fats
Pyrazinamide
Ethambutol
United States Food and Drug Administration
Rifampin
Aluminum
Magnesium
Volunteers
Stomach
High Pressure Liquid Chromatography
Serum

Keywords

  • Antacids
  • Bioavailability
  • Food
  • Isoniazid
  • Mycobacterium tuberculosis
  • Pharmacokinetics

ASJC Scopus subject areas

  • Pulmonary and Respiratory Medicine

Cite this

Pharmacokinetics of isoniazid under fasting conditions, with food, and with antacids. / Peloquin, Charles A.; Namdar, R.; Dodge, A. A.; Nix, David E.

In: International Journal of Tuberculosis and Lung Disease, Vol. 3, No. 8, 08.1999, p. 703-710.

Research output: Contribution to journalArticle

@article{88e07cfeb55a4e9fa17c26ca1475adf2,
title = "Pharmacokinetics of isoniazid under fasting conditions, with food, and with antacids",
abstract = "STUDY OBJECTIVES: To determine the intra- and intersubject variability in and the effects of food or antacids on the pharmacokinetics of isoniazid (INH). DESIGN: Randomized, four-period cross-over Phase I study in 14 healthy male and female volunteers. Subjects ingested single doses of INH 300 mg under fasting conditions twice, with a high-fat meal, and with aluminum- magnesium antacid. They also received standard doses of rifampin, pyrazinamide, and ethambutol. RESULTS: Serum was collected for 48 hours, and assayed by high performance liquid chromatography (HPLC). Data were analyzed using noncompartmental methods and a compartmental analysis using nonparametric expectation maximization. Both fasting conditions produced similar results: a mean INH C(max) of 5.53 ± 2.92 μg/ml, T(max) of 1.02 ± 1.10 hours, and AUC(0-∞) of 20.16 ± 12.45 μg* hr/ml. These findings are similar to those reported previously. Antacids did not alter these parameters significantly (C(max) of 5.62 ± 2.53 μg/ml, T(max) of 0.71 ± 0.56 hours, and AUC(0-∞) of 20.27 ± 11.39 μg* hr/ml). In contrast, the high-fat meal recommended by the Food and Drug Administration reduced INH C(max) by 51{\%} (2.73 ± 1.70 μg/ml), nearly doubled T(max) (1.93 ± 1.61 hours), and reduced AUC(0-∞) by 12{\%} (17.72 ± 10.32 μg*hr/ml). CONCLUSIONS: These changes in C(max), T(max), and AUC(0-∞) can be avoided by giving INH on an empty stomach whenever possible.",
keywords = "Antacids, Bioavailability, Food, Isoniazid, Mycobacterium tuberculosis, Pharmacokinetics",
author = "Peloquin, {Charles A.} and R. Namdar and Dodge, {A. A.} and Nix, {David E.}",
year = "1999",
month = "8",
language = "English (US)",
volume = "3",
pages = "703--710",
journal = "International Journal of Tuberculosis and Lung Disease",
issn = "1027-3719",
publisher = "International Union against Tubercul. and Lung Dis.",
number = "8",

}

TY - JOUR

T1 - Pharmacokinetics of isoniazid under fasting conditions, with food, and with antacids

AU - Peloquin, Charles A.

AU - Namdar, R.

AU - Dodge, A. A.

AU - Nix, David E.

PY - 1999/8

Y1 - 1999/8

N2 - STUDY OBJECTIVES: To determine the intra- and intersubject variability in and the effects of food or antacids on the pharmacokinetics of isoniazid (INH). DESIGN: Randomized, four-period cross-over Phase I study in 14 healthy male and female volunteers. Subjects ingested single doses of INH 300 mg under fasting conditions twice, with a high-fat meal, and with aluminum- magnesium antacid. They also received standard doses of rifampin, pyrazinamide, and ethambutol. RESULTS: Serum was collected for 48 hours, and assayed by high performance liquid chromatography (HPLC). Data were analyzed using noncompartmental methods and a compartmental analysis using nonparametric expectation maximization. Both fasting conditions produced similar results: a mean INH C(max) of 5.53 ± 2.92 μg/ml, T(max) of 1.02 ± 1.10 hours, and AUC(0-∞) of 20.16 ± 12.45 μg* hr/ml. These findings are similar to those reported previously. Antacids did not alter these parameters significantly (C(max) of 5.62 ± 2.53 μg/ml, T(max) of 0.71 ± 0.56 hours, and AUC(0-∞) of 20.27 ± 11.39 μg* hr/ml). In contrast, the high-fat meal recommended by the Food and Drug Administration reduced INH C(max) by 51% (2.73 ± 1.70 μg/ml), nearly doubled T(max) (1.93 ± 1.61 hours), and reduced AUC(0-∞) by 12% (17.72 ± 10.32 μg*hr/ml). CONCLUSIONS: These changes in C(max), T(max), and AUC(0-∞) can be avoided by giving INH on an empty stomach whenever possible.

AB - STUDY OBJECTIVES: To determine the intra- and intersubject variability in and the effects of food or antacids on the pharmacokinetics of isoniazid (INH). DESIGN: Randomized, four-period cross-over Phase I study in 14 healthy male and female volunteers. Subjects ingested single doses of INH 300 mg under fasting conditions twice, with a high-fat meal, and with aluminum- magnesium antacid. They also received standard doses of rifampin, pyrazinamide, and ethambutol. RESULTS: Serum was collected for 48 hours, and assayed by high performance liquid chromatography (HPLC). Data were analyzed using noncompartmental methods and a compartmental analysis using nonparametric expectation maximization. Both fasting conditions produced similar results: a mean INH C(max) of 5.53 ± 2.92 μg/ml, T(max) of 1.02 ± 1.10 hours, and AUC(0-∞) of 20.16 ± 12.45 μg* hr/ml. These findings are similar to those reported previously. Antacids did not alter these parameters significantly (C(max) of 5.62 ± 2.53 μg/ml, T(max) of 0.71 ± 0.56 hours, and AUC(0-∞) of 20.27 ± 11.39 μg* hr/ml). In contrast, the high-fat meal recommended by the Food and Drug Administration reduced INH C(max) by 51% (2.73 ± 1.70 μg/ml), nearly doubled T(max) (1.93 ± 1.61 hours), and reduced AUC(0-∞) by 12% (17.72 ± 10.32 μg*hr/ml). CONCLUSIONS: These changes in C(max), T(max), and AUC(0-∞) can be avoided by giving INH on an empty stomach whenever possible.

KW - Antacids

KW - Bioavailability

KW - Food

KW - Isoniazid

KW - Mycobacterium tuberculosis

KW - Pharmacokinetics

UR - http://www.scopus.com/inward/record.url?scp=0032773961&partnerID=8YFLogxK

UR - http://www.scopus.com/inward/citedby.url?scp=0032773961&partnerID=8YFLogxK

M3 - Article

C2 - 10460103

AN - SCOPUS:0032773961

VL - 3

SP - 703

EP - 710

JO - International Journal of Tuberculosis and Lung Disease

JF - International Journal of Tuberculosis and Lung Disease

SN - 1027-3719

IS - 8

ER -