Rabbit Anti-Hydrocodone Polyclonal antibody

The US FDA has encouraged the development of abuse-deterrent formulations (ADFs) of opioid analgesics as one component in a comprehensive effort to combat prescription opioid abuse. Guidance issued by the FDA outlines three types of premarket studies for evaluating abuse deterrence: laboratory-based in vitro manipulation and extraction studies, pharmacokinetic studies and human abuse potential studies. After approval, postmarket studies are needed to evaluate the impact of an ADF product on abuse in real-world settings. This review summarizes the regulatory issues involved in the development of ADF opioids and clarifies abuse-deterrence claims in product labels, in order to assist clinicians in critically evaluating the available evidence pertaining to the abuse-deterrent features of opioid analgesics.

Two open-label, single-dose, parallel-group studies assessed effects of renal and hepatic impairment on the pharmacokinetics of a hydrocodone extended-release (ER) formulation developed with the CIMA Abuse-Deterrence Technology platform. Forty-eight subjects with normal renal function or varying degrees of renal impairment received hydrocodone ER 45 mg (study 1); 16 subjects with normal hepatic function or moderate hepatic impairment received hydrocodone ER 15 mg (study 2). Blood samples were obtained predose and through 144 hours postdose. Mean maximum observed plasma hydrocodone concentration (C-max) in subjects with normal renal function, mild, moderate, and severe impairment, and end-stage renal disease was 28.6, 33.4, 42.4, 36.5, and 31.6 ng/mL, and mean area under the plasma hydrocodone concentration-versus-time curve from time 0 to infinity (AUC(0-infinity)) was 565, 660, 973, 983, and 638 ng center dot h/mL, respectively. Incidence of adverse events was 57%, 38%, 44%, 33%, and 56%, respectively. Mean C-max with normal hepatic function and moderate impairment was 10.1 and 13.0 ng/mL, and mean AUC(0-infinity) was 155 and 269 ng center dot h/mL, respectively. Incidence of adverse events was 38% in both groups. Altered systemic exposure in renally or hepatically impaired populations (up to similar to 70% higher) should be considered when titrating to an effective dose of hydrocodone ER.