Pharmacokinetics of cycloserine under fasting conditions and with high-fat meal, orange juice, and antacids

M. Zhu, David E. Nix, R. D. Adam, J. M. Childs, C. A. Peloquin

Research output: Contribution to journalArticle

47 Citations (Scopus)

Abstract

Study Objectives. To determine the effect of a high-fat meal, orange juice, and antacids on absorption of a single oral dose of cycloserine and to estimate its population pharmacokinetic parameters. Design. Randomized, four-period, crossover study. Setting. Clinical research center. Patients. Twelve healthy volunteers. Interventions. Subjects received single doses of cycloserine 500 mg after a 12-hour fast (reference), with a high-fat meal, with orange juice, and with antacids. They also received clofazimine 200 mg, ethionamide 500 mg, and p-aminosalicylic acid granules 6000 mg. Measurements and Main Results. Plasma samples were collected for 48 hours and assayed by validated high-performance capillary electrophoresis assay. Concentration-time data were analyzed with noncompartmental, one-compartment, and population methods. The maximum concentration (Cmax) of cycloserine was decreased (p=0.02) by the high-fat meal. No other statistically significant differences were observed for Cmax and area under the curve from time zero to infinity across the four treatments. The high-fat meal significantly (p<0.0001) delayed time to maximum concentration by 4.7 times compared with that of the reference (1.1 hr). Conclusion. The pharmacokinetics of cycloserine were minimally affected by orange juice and antacids, whereas the high-fat meal delayed absorption. Administering cycloserine without a high-fat meal avoids potential alterations in the pattern of absorption.

Original languageEnglish (US)
Pages (from-to)891-897
Number of pages7
JournalPharmacotherapy
Volume21
Issue number8
StatePublished - 2001
Externally publishedYes

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Cycloserine
Antacids
Meals
Fasting
Pharmacokinetics
Fats
Ethionamide
Aminosalicylic Acid
Clofazimine
Capillary Electrophoresis
Cross-Over Studies
Population
Area Under Curve
Healthy Volunteers
Research

ASJC Scopus subject areas

  • Pharmacology (medical)
  • Pharmacology, Toxicology and Pharmaceutics(all)

Cite this

Pharmacokinetics of cycloserine under fasting conditions and with high-fat meal, orange juice, and antacids. / Zhu, M.; Nix, David E.; Adam, R. D.; Childs, J. M.; Peloquin, C. A.

In: Pharmacotherapy, Vol. 21, No. 8, 2001, p. 891-897.

Research output: Contribution to journalArticle

Zhu, M. ; Nix, David E. ; Adam, R. D. ; Childs, J. M. ; Peloquin, C. A. / Pharmacokinetics of cycloserine under fasting conditions and with high-fat meal, orange juice, and antacids. In: Pharmacotherapy. 2001 ; Vol. 21, No. 8. pp. 891-897.
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N2 - Study Objectives. To determine the effect of a high-fat meal, orange juice, and antacids on absorption of a single oral dose of cycloserine and to estimate its population pharmacokinetic parameters. Design. Randomized, four-period, crossover study. Setting. Clinical research center. Patients. Twelve healthy volunteers. Interventions. Subjects received single doses of cycloserine 500 mg after a 12-hour fast (reference), with a high-fat meal, with orange juice, and with antacids. They also received clofazimine 200 mg, ethionamide 500 mg, and p-aminosalicylic acid granules 6000 mg. Measurements and Main Results. Plasma samples were collected for 48 hours and assayed by validated high-performance capillary electrophoresis assay. Concentration-time data were analyzed with noncompartmental, one-compartment, and population methods. The maximum concentration (Cmax) of cycloserine was decreased (p=0.02) by the high-fat meal. No other statistically significant differences were observed for Cmax and area under the curve from time zero to infinity across the four treatments. The high-fat meal significantly (p<0.0001) delayed time to maximum concentration by 4.7 times compared with that of the reference (1.1 hr). Conclusion. The pharmacokinetics of cycloserine were minimally affected by orange juice and antacids, whereas the high-fat meal delayed absorption. Administering cycloserine without a high-fat meal avoids potential alterations in the pattern of absorption.

AB - Study Objectives. To determine the effect of a high-fat meal, orange juice, and antacids on absorption of a single oral dose of cycloserine and to estimate its population pharmacokinetic parameters. Design. Randomized, four-period, crossover study. Setting. Clinical research center. Patients. Twelve healthy volunteers. Interventions. Subjects received single doses of cycloserine 500 mg after a 12-hour fast (reference), with a high-fat meal, with orange juice, and with antacids. They also received clofazimine 200 mg, ethionamide 500 mg, and p-aminosalicylic acid granules 6000 mg. Measurements and Main Results. Plasma samples were collected for 48 hours and assayed by validated high-performance capillary electrophoresis assay. Concentration-time data were analyzed with noncompartmental, one-compartment, and population methods. The maximum concentration (Cmax) of cycloserine was decreased (p=0.02) by the high-fat meal. No other statistically significant differences were observed for Cmax and area under the curve from time zero to infinity across the four treatments. The high-fat meal significantly (p<0.0001) delayed time to maximum concentration by 4.7 times compared with that of the reference (1.1 hr). Conclusion. The pharmacokinetics of cycloserine were minimally affected by orange juice and antacids, whereas the high-fat meal delayed absorption. Administering cycloserine without a high-fat meal avoids potential alterations in the pattern of absorption.

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