Clinical Pharmacology and Pharmacokinetics of Once‐Daily Hydromorphone Hydrochloride Extended‐Release Capsules

Hydromorphone hydrochloride extended release (HHER) is a multiparticulate melt‐extrusion pellet capsule formulation administered q24h. Study 1 investigated the bioavailability of 24‐mg HHER fed, as well as 24‐mg and 12‐mg HHER and 8‐mg hydromorphone hydrochloride immediate‐release (HHIR) tablets fasting. No clinically significant food effect was observed on hydromorphone Cmax or AUC for the 24‐mg HHER, and dose proportionality (AUC) was demonstrated between 12‐ and 24‐mg HHER. Study 2 demonstrated dose strength proportionality for 3 ± 12‐mg HHER versus 1 ± 32‐mg HHER. Study 3 evaluated 12‐mg HHER q24h versus 3‐mg HHIR q6h at steady state. HHER produced relatively constant steady‐state concentrations over 24 hours. HHER and HHIR were equivalent for AUCss. Cssmax was 26% lower for HHER than HHIR, Cssmin was 43% higher for HHER, and peak‐to‐trough fluctuation was 126% for HHER versus 328% for HHIR, which are ideal attributes of a once‐daily oral extended‐ release dosage form. HHER administration resulted in fewer adverse events than HHIR in study 3.