Abstract
We compared a new coated-particle formulation of valproate (Depakote Sprinkle) capsules with valproic acid (Depakene) syrup for bioavailability, side effects, and patient and parent preference. Twelve children with epilepsy, aged 5 to 16 years, participated in this randomized, two-period, crossover study. They were assigned to a 7-day regimen with one formulation and then crossed over to the other; the drug was given every 12 hours. On day 7, blood samples collected during a 12-hour period were analyzed for the presence of valproate. At the study's end, parents and children were asked structured questions regarding formulation preference and adverse events. The extent of absorption from sprinkle equaled that from syrup (relative bioavailability=1.02), but absorption was slower (time to maximum concentration=4.2 vs 0.9 hour; p<0.01). Fluctuations in serum concentrations were less with sprinkle (34.8% vs 62.3%; p<0.01). Sprinkle was preferred by 9 of the 12 parents because of ease of administration, and by nine of the children because of improved palatability. We conclude that sprinkle may be substituted for syrup without changing the daily dose. Furthermore, sprinkle, because of its prolonged absorption, may be given every 12 hours to children receiving monotherapy. Compliance may be enhanced because of the more convenient dosing schedules and the high degree of patient and parent acceptance.
| Original language | English (US) |
|---|---|
| Pages (from-to) | 634-638 |
| Number of pages | 5 |
| Journal | The Journal of pediatrics |
| Volume | 120 |
| Issue number | 4 PART 1 |
| DOIs | |
| State | Published - Apr 1992 |
Bibliographical note
Funding Information:Valproic acid is an antiepileptic drug frequently prescribed to control seizure disorders in both children and adults. However, the syrup has an unpleasant taste and occasionally causes gastrointestinal distress, as does the capsule.l, 2 Rapid absorption of the syrup contributes to marked fluctuations in serum valproate concentrations. Although the Supported in part by a grant from Abbott Laboratories. Presented in part at the annual meeting of the American Epilepsy Society, Baltimore, Md., Dec. 7, 1987. Submitted for publication July 31, 1991; accepted Nov. 19, 199 l. Reprint requests: James C. Cloyd, PharmD, HSUF--7115, College of Pharmacy, University of Minnesota, 308 Harvard St., Minneapolis, MN 55455. 9/25/35164 enteric-coated formulation reduces the frequency of gastrointestinal complaints, it does not lessen fluctuations in serum concentrations, a, 3 As a result, some clinicians recommend giving valproate three or four times daily. 4 We