Premium
Pharmacokinetics of Cycloserine under Fasting Conditions and with High‐Fat Meal, Orange Juice, and Antacids
Author(s) -
Zhu Min,
Nix David E.,
Adam Rodney D.,
Childs James M.,
Peloquin Charles A.
Publication year - 2001
Publication title -
pharmacotherapy: the journal of human pharmacology and drug therapy
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.227
H-Index - 109
eISSN - 1875-9114
pISSN - 0277-0008
DOI - 10.1592/phco.21.11.891.34524
Subject(s) - meal , cycloserine , pharmacokinetics , cmax , chemistry , orange juice , population , crossover study , food science , pharmacology , zoology , medicine , placebo , biochemistry , biology , antibiotics , alternative medicine , environmental health , pathology
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 (C max ) of cycloserine was decreased (p=0.02) by the high‐fat meal. No other statistically significant differences were observed for C max 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.