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.
RCT Entities:
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.
Authors: Elizabeth J Santa Ana; Bruce J Rounsaville; Tami L Frankforter; Charla Nich; Theresa Babuscio; James Poling; Kishorchandra Gonsai; Kevin P Hill; Kathleen M Carroll Journal: Drug Alcohol Depend Date: 2009-07-09 Impact factor: 4.492
Authors: Lauren A M Lebois; Antonia V Seligowski; Jonathan D Wolff; Sarah B Hill; Kerry J Ressler Journal: Annu Rev Clin Psychol Date: 2019-01-30 Impact factor: 18.561