Premium
Effect of Food on the Pharmacokinetics of Rifalazil, a Novel Antibacterial, in Healthy Male Volunteers
Author(s) -
Chen Y.X.,
Cabana B.,
Kivel N.,
Michaelis A.
Publication year - 2007
Publication title -
the journal of clinical pharmacology
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 0.92
H-Index - 116
eISSN - 1552-4604
pISSN - 0091-2700
DOI - 10.1177/0091270007300745
Subject(s) - pharmacokinetics , bioequivalence , cmax , crossover study , calorie , medicine , pharmacology , zoology , food science , chemistry , biology , placebo , alternative medicine , pathology
Rifalazil is a new antibiotic structurally related to rifampin but devoid of the metabolic liabilities typically associated with the rifamycin class of antibiotics. A randomized, 3‐way crossover study in healthy male volunteers (n = 12) investigated the safety and pharmacokinetics of a single 25‐mg oral rifalazil dose administered under a standard breakfast containing fat as 30% of calories, a high‐fat breakfast containing fat as 60% of calories, and an overnight fast of 10 hours with a 21‐ to 28‐day washout between doses. Systemic exposure to rifalazil based on C max , AUC 0‐Tlast , and AUC 0‐∞ was increased progressively as the fat content of the test breakfast was increased from 30% to 60% compared with fasting. The confidence intervals for both fat‐containing breakfasts are outside the limits of 80% to 125% allowed for food effect bioequivalence based on C max , AUC 0‐Tlast , and AUC 0‐∞ . This food effect may be a result of increased fractional absorption with increasing dietary fat content. Another striking finding was the large reduction of the pharmacokinetic intersubject variability after rifalazil administration with food. Rifalazil was safe and well tolerated under fed and fasted conditions.