Pharmacokinetics of Cycloserine under Fasting Conditions and with High-Fat Meal, Orange Juice, and Antacids
Article first published online: 17 JAN 2012
2001 Pharmacotherapy Publications Inc.
Pharmacotherapy: The Journal of Human Pharmacology and Drug Therapy
Volume 21, Issue 8, pages 891–897, August 2001
How to Cite
Zhu, M., Nix, D. E., Adam, R. D., Childs, J. M. and Peloquin, C. A. (2001), Pharmacokinetics of Cycloserine under Fasting Conditions and with High-Fat Meal, Orange Juice, and Antacids. Pharmacotherapy, 21: 891–897. doi: 10.1592/phco.21.11.891.34524
- Issue published online: 17 JAN 2012
- Article first published online: 17 JAN 2012
- Manuscript received February 26, 2001; Accepted May 25, 2001
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.