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 C(max) 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 x 12-mg HHER versus 1 x 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 AUC(ss). C(ssmax) was 26% lower for HHER than HHIR, C(ssmin) 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.
Vashi
Vijay
V
Purdue Pharma, LP, One Stamford Forum, Stamford, CT 06901-3431, USA.
Harris
Stephen
S
El-Tahtawy
Ahmed
A
Wu
Danlin
D
Cipriano
Alessandra
A
D000328:Adult; D000701:Analgesics, Opioid / Q000008:administration & dosage / Q000009:adverse effects / Q000493:pharmacokinetics*; D019540:Area Under Curve; D001682:Biological Availability; D018592:Cross-Over Studies; D003692:Delayed-Action Preparations; D004305:Dose-Response Relationship, Drug; D004334:Drug Administration Schedule; D005260:Female; D018565:Food-Drug Interactions; D006207:Half-Life; D006801:Humans; D004091:Hydromorphone / Q000008:administration & dosage / Q000009:adverse effects / Q000493:pharmacokinetics*; D008297:Male
D000701:Analgesics, Opioid; D003692:Delayed-Action Preparations; D004091:Hydromorphone