TY - JOUR
T1 - Pharmacokinetics of cycloserine under fasting conditions and with high-fat meal, orange juice, and antacids
AU - Zhu, M.
AU - Nix, D. E.
AU - Adam, R. D.
AU - Childs, J. M.
AU - Peloquin, C. A.
PY - 2001
Y1 - 2001
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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U2 - 10.1592/phco.21.11.891.34524
DO - 10.1592/phco.21.11.891.34524
M3 - Article
C2 - 11718495
AN - SCOPUS:0034885352
SN - 0277-0008
VL - 21
SP - 891
EP - 897
JO - Pharmacotherapy
JF - Pharmacotherapy
IS - 8
ER -