title: Comparative study of different brands of stavudine capsules for the off-label 'opened capsule' dosing method recommended for HIV-infected infants and children in resource-limited settings.
abstract: INTRODUCTION: If a caregiver does not have access to a refrigerator, the South African National Department of Health advises that stavudine adult capsule formulations be employed using the off-label 'opened capsule' dosing method. The accuracy of this dosing method has not previously been validated.  AIM: To assess the accuracy of the off-label opened capsule method for stavudine dosing in infants and children. In addition, we assessed the relative ease of dispersion of generic and original capsule preparations in water to determine which preparations, if any, are suitable for the off-label opened capsule dosing method.  METHOD: We evaluated 10 Zerit (Bristol-Myers Squibb), 5 Stavudine (Aspen), and 5 Stavir (Cipla) capsules. Each capsule was dispersed in 30 ml water, creating 20 separate solutions. Timed dispersion of each generic was compared with that of the original (Zerit). Each solution was then centrifuged to remove sediment, and the concentration of active drug (mg/ml) was analysed by high-performance liquid chromatography.  RESULTS: The ease of dispersion of the contents of Aspen Stavudine capsules was equivalent to that of Zerit, and resulted in a mean recovery of active drug from solution of over 97%, confirming the accuracy of this dosing method. The contents of Stavir capsules, however, were extremely difficult to disperse in water despite prolonged agitation; consequently, the recovery of active drug from the solution was reduced.  CONCLUSION: The accuracy of the off-label opened capsule dosing method for stavudine is acceptable. There is no need to instruct caregivers to include sediment in the aliquot given to the infant. However, studies that confirm adequate bioavailability and efficacy are needed. In addition, it is important to avoid supplying generic capsules the contents of which do not disperse easily in water, as this may lead to a significant reduction in the amount of active drug that a child receives.
authors.affiliation: KID-CRU (Children's Infectious Diseases Clinical Research Unit), Tygerberg Academic Hospital, W Cape.
authors.forename: Steve
authors.initials: S
authors.lastname: Innes
authors.forename: Marlize
authors.initials: M
authors.lastname: Smuts
authors.forename: Mark F
authors.initials: MF
authors.lastname: Cotton
authors.forename: Heiner
authors.initials: H
authors.lastname: Seifart
authors.forename: Bernd
authors.initials: B
authors.lastname: Rosenkranz