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

Pharmacotherapy. 2001 Aug;21(8):891-7. doi: 10.1592/phco.21.11.891.34524.


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.

Publication types

  • Clinical Trial
  • Randomized Controlled Trial
  • Research Support, U.S. Gov't, P.H.S.

MeSH terms

  • Administration, Oral
  • Adult
  • Aminosalicylic Acid / pharmacology
  • Antacids / pharmacology*
  • Antibiotics, Antitubercular / administration & dosage
  • Antibiotics, Antitubercular / adverse effects
  • Antibiotics, Antitubercular / pharmacokinetics*
  • Area Under Curve
  • Beverages
  • Citrus
  • Clofazimine / pharmacology
  • Cross-Over Studies
  • Cycloserine / administration & dosage
  • Cycloserine / adverse effects
  • Cycloserine / pharmacokinetics*
  • Dietary Fats / pharmacology*
  • Drug Interactions
  • Electrophoresis, Capillary
  • Ethionamide / pharmacology
  • Fasting / physiology*
  • Female
  • Food-Drug Interactions*
  • Humans
  • Intestinal Absorption / drug effects
  • Male


  • Antacids
  • Antibiotics, Antitubercular
  • Dietary Fats
  • Aminosalicylic Acid
  • Cycloserine
  • Clofazimine
  • Ethionamide