Influence of Ramadan on the pharmacokinetics of a single oral dose of valproic acid administered at two different times

This study was carried out in healthy volunteers in order to examine the influence of changes in eating and rest/activity rhythms during Ramadan on the pharmacokinetics of valproic acid (VPA; Depakine). A single oral dose of 800 mg was administered to the first group of subjects (n = 7) at 8:00 PM and to the second group (n = 5) at 5:00 AM. Each group was submitted to three treatment phases: the first was carried out 3 weeks prior to Ramadan (PR), the second one at the end of the first week of Ramadan (R1) and the last at the end of the third week of Ramadan (R3). The plasma kinetics of VPA were determined for each treatment schedule throughout the 50 h following drug intake. During Ramadan, a significant decrease was observed in the Cmax (56.22 +/- 5.32 mg/l in PR vs. 48.35 +/- 5.07 mg/l in R3; p < 0.05) and in the AUC(0.50 h) (1429.92 +/- 284.23 in PR vs. 1090.26 +/- 277.73 mg.h/l in R3; p < 0.05) for the 8:00 PM intake. For the 5:00 AM intake, a significant decrease was observed in the t1/2 (12.15 +/- 1.45 h in PR vs. 9.55 +/- 1.97 h in R3; p < 0.05) and AUC(0.50 h) values (1241.29 +/- 239.01 mg.h/l in PR vs. 1019.21 +/- 256.86 mg.h/l in R3; p < 0.05). These parameters showed a significant decrease at the end of the third week of Ramadan (R3), compared to the control period (PR).