Effect of food on systemic exposure to niflumic acid following postprandial administration of talniflumate.
OBJECTIVE
Talniflumate was designed as a prodrug of niflumic acid, a potent analgesic and anti-inflammatory drug, which is widely prescribed for treating rheumatoid diseases. The prandial effect on talniflumate absorption remains unclear; therefore, this study investigated the effect of food on the systemic exposure to niflumic acid in healthy volunteers.


METHODS
Volunteers received a single 740-mg dose of talniflumate 30 min after consuming a high-fat breakfast, a low-fat breakfast, or no food (fasting condition). Plasma concentrations of both talniflumate and niflumic acid were measured using validated high-performance liquid chromatography coupled to tandem mass spectrometry.


RESULTS
The maximum concentration of niflumic acid was 224 +/- 193 ng/ml at approximately 2.7 h in the fasted condition compared with 886 +/- 417 ng/ml (p < 0.05) at 1.8 h and 1,159 +/- 508 ng/ml (p < 0.01) at 2.2 h with the low- and high-fat meals, respectively. The mean area under the curve from zero to infinity (AUC(inf)) values after the low- and high-fat meals were four- and fivefold, respectively, the value while fasting (p < 0.05).


CONCLUSIONS
It is strongly recommended that talniflumate be taken after a meal to increase systemic exposure to its active metabolite. Our results suggest a reduction in the daily dosage of talniflumate when taken with food.
Kang
Wonku
W
College of Pharmacy, Catholic University of Daegu, Kyoungbuk, Korea. wonkuk@cu.ac.kr
Kim
Kibum
K
Kim
Eun-Young
EY
Kwon
Kwang-il
KI
Bang
Jun Seok
JS
Yoon
Young-Ran
YR
D000284:Administration, Oral; D000328:Adult; D000894:Anti-Inflammatory Agents, Non-Steroidal / Q000097:blood / Q000493:pharmacokinetics*; D019540:Area Under Curve; D001572:Benzofurans / Q000008:administration & dosage* / Q000097:blood / Q000493:pharmacokinetics; D001682:Biological Availability; D018592:Cross-Over Studies; D005215:Fasting; D005502:Food; D018565:Food-Drug Interactions; D006207:Half-Life; D006801:Humans; D008297:Male; D009544:Niflumic Acid / Q000097:blood / Q000493:pharmacokinetics*; D019518:Postprandial Period; D011355:Prodrugs / Q000008:administration & dosage* / Q000493:pharmacokinetics; D011725:Pyridines / Q000008:administration & dosage* / Q000097:blood / Q000493:pharmacokinetics; D055815:Young Adult
D000894:Anti-Inflammatory Agents, Non-Steroidal; D001572:Benzofurans; D011355:Prodrugs; D011725:Pyridines; D009544:Niflumic Acid; C488233:talniflumate