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


METHODS
Randomized, four-period, crossover study.


METHODS
Clinical research center.


METHODS
Twelve healthy volunteers.


METHODS
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.


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).


CONCLUSIONS
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.
Zhu
M
M
Department of Medicine, National Jewish Medical and Research Center, Denver, Colorado 80206, USA.
Nix
D E
DE
Adam
R D
RD
Childs
J M
JM
Peloquin
C A
CA
D000284:Administration, Oral; D000328:Adult; D010131:Aminosalicylic Acid / Q000494:pharmacology; D000863:Antacids / Q000494:pharmacology*; D000904:Antibiotics, Antitubercular / Q000008:administration & dosage / Q000009:adverse effects / Q000493:pharmacokinetics*; D019540:Area Under Curve; D001628:Beverages; D002957:Citrus; D002991:Clofazimine / Q000494:pharmacology; D018592:Cross-Over Studies; D003523:Cycloserine / Q000008:administration & dosage / Q000009:adverse effects / Q000493:pharmacokinetics*; D004041:Dietary Fats / Q000494:pharmacology*; D004347:Drug Interactions; D019075:Electrophoresis, Capillary; D005000:Ethionamide / Q000494:pharmacology; D005215:Fasting / Q000502:physiology*; D005260:Female; D018565:Food-Drug Interactions; D006801:Humans; D007408:Intestinal Absorption / Q000187:drug effects; D008297:Male
D000863:Antacids; D000904:Antibiotics, Antitubercular; D004041:Dietary Fats; D010131:Aminosalicylic Acid; D003523:Cycloserine; D002991:Clofazimine; D005000:Ethionamide