Isotretinoin conundrum: a randomized, openlabel, crossover study in Mexico to evaluate the bioavailability and bioequivalence of three pharmaceutical preparations of isotretinoin in healthy participants.
Int J Clin Pharmacol Ther
; 53(10): 897-904, 2015 Oct.
Article
em En
| MEDLINE
| ID: mdl-26308169
ABSTRACT
OBJECTIVE:
The oral retinoid agent isotretinoin (13-cis-retinoic acid) is approved for the treatment of severe recalcitrant cystic acne. For registrational renewal of Oratane® in Mexico (isotretinoin; Laboratorios Dermatologicos Darier S.A. de C.V., Mexico), it was necessary to establish bioequivalence to the reference product Roaccutan® (Isotretinoin; Roche, Mannheim, Germany). Three prior studies failed to establish the bioequivalence of Oratane to Mexican-sourced Roaccutan. However, 13 studies demonstrated the bioequivalence of Oratane to Roaccutane® from multiple sources. This study compared the bioavailability of Oratane with that of Mexicansourced Roaccutan and Australian-sourced Roaccutane.METHODS:
Study participants received each of the three agents in a randomized, open-label, 6-sequence, 3-way crossover study with a 2-week washout period between treatments.RESULTS:
Pharmacokinetic analysis revealed that peak plasma concentration (Cmax) and area under the plasma concentration-time curve from time 0 (dosing) to infinite time (AUC0-∞) were lower for Roaccutan than for Roaccutane and Oratane (Cmax 1,023.35, 1,223.08, and 1,224.25 ng/mL, respectively; AUC0-∞ 13,653.65, 15,681.35 and 15,733.55 ng/mL x h, respectively). The 90% CIs (test/reference) for the ratios of the geometric means indicated that Oratane was bioequivalent to Roaccutane but not to Roaccutan. In addition, Roaccutane (R2) was not bioequivalent to Roaccutan (R1; R1/R2 90% CIs Cmax, 76.12 - 91.04; AUC0-t, 82.19 - 91.13; AUC0-∞, 82.94 - 91.57).CONCLUSION:
Oratane and Australian-sourced Roaccutane could be considered bioequivalent, but neither formulation was found to be bioequivalent to Mexican-sourced Roaccutan.
Texto completo:
1
Base de dados:
MEDLINE
Assunto principal:
Isotretinoína
Tipo de estudo:
Clinical_trials
Limite:
Adult
/
Humans
/
Male
País como assunto:
Mexico
Idioma:
En
Ano de publicação:
2015
Tipo de documento:
Article