The influence of food on the disposition of the antiepileptic rufinamide in healthy volunteers

Abstract

The effect of food on the pharmacokinetics of the antiepileptic rufinamide was investigated in healthy volunteers. Twelve subjects were treated with single per‐oral doses of 600 mg of rufinamide after overnight fasting or a fat and protein rich breakfast. Mean (±S.D.) areas under the plasma concentration–time curves (AUCs) of the unchanged compound were 57.2 (16) μg mL−1 h when given to the fasted volunteers and 81.7 (22.2) μg mL−1 h (p = 0.0001) when given after the breakfast. The average AUC was increased by 44% when rufinamide was given with food and the maximum concentration (Cmax) by about 100%. The time at which Cmax was reached (tmax) was shorter (8 h in fasted conditions and 6 h in fed after breakfast); the terminal half‐life was not influenced by concomitant intake of food. © 1998 John Wiley & Sons, Ltd.

Rufinamide

“…There is moderate intersubject variability. The extent of bioavailability of rufinamide is modestly affected by food, as shown by comparing exposure after single doses under fed and fasted conditions 5 ; however, food has no effect upon repeat dosing. Rufinamide has low protein binding (approximately 34%), and its apparent volume of distribution after an oral dose is on the order of total body water (50 -80 L).…”

Effects of Food on Drug Absorption

“…Gemifloxacin for bacterial infections and stavudine therapy for human immunodeficiency virus (HIV)-infected patients are good examples of drugs administered without food restriction (Kaul et al ., 1998;Allen et al ., 2000). However, there are exceptions; rufinamide exhibits higher fluctuations in the fed state when compared with the fasted state, and, yet, it is recommended to be administered, with supervision, in the fed state owing to the attainment of higher plasma concentrations (Cardot et al ., 1998).…”

“…Fed state drug administration can affect one or more pharmacokinetic parameters (T max , C max , and AUC 0 -∞ ) of a drug when compared with fasted state drug administration (Singh, 1999). For example, food was shown to delay and increase the absorption of diprafenone (Koytchev et al ., 1996); accelerate and increase the absorption of rufinamide (Cardot et al ., 1998); and delay and decrease the absorption of avitriptan (Marathe et al ., 1998). Therefore, for simplicity purpose drugs may be classified to exhibit positive, negative, or no food effects based on the changes observed with respect to only one pharmacokinetic parameter, the AUC 0 -∞ , since AUC 0 -∞ reflects the extent of absorption of a drug and defines the effectiveness of a therapy.…”

Rufinamide: a new anti-epileptic medication

“…In a preliminary study of 12 healthy volunteers in fasted and fed states given 600 mg of rufinamide, food increased absorption (AUC 81.7 versus 57.2 mcg/ml/h, 44% higher in fed state), and shortened T max (6 versus 8 h) and increased C max (4.29 versus 2.19 mcg/ml/h, 100% higher in the fed state). In the fed state peak plasma concentration was reached in 5 -6 h, independent of dose [7] . Side effects were Table 2 Side effects See Table 4 Dosing 1933 also more common in patients in the fed state.…”