title: Effects of Renal Impairment and Hepatic Impairment on the Pharmacokinetics of Hydrocodone After Administration of a Hydrocodone Extended-Release Tablet Formulated With Abuse-Deterrence Technology.
abstract: 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 (Cmax ) 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 (AUC0-∞ ) was 565, 660, 973, 983, and 638 ng·h/mL, respectively. Incidence of adverse events was 57%, 38%, 44%, 33%, and 56%, respectively. Mean Cmax with normal hepatic function and moderate impairment was 10.1 and 13.0 ng/mL, and mean AUC0-∞ was 155 and 269 ng·h/mL, respectively. Incidence of adverse events was 38% in both groups. Altered systemic exposure in renally or hepatically impaired populations (up to ∼70% higher) should be considered when titrating to an effective dose of hydrocodone ER.
authors.affiliation: Sci-Med Bridge, LLC, Malvern, PA, USA.
authors.forename: Mona
authors.initials: M
authors.lastname: Darwish
authors.affiliation: Teva Pharmaceuticals, Frazer, PA, USA.
authors.forename: Ronghua
authors.initials: R
authors.lastname: Yang
authors.affiliation: Teva Pharmaceuticals, West Chester, PA, USA.
authors.forename: William
authors.initials: W
authors.lastname: Tracewell
authors.affiliation: Teva Pharmaceuticals, West Chester, PA, USA.
authors.forename: Philmore
authors.initials: P
authors.lastname: Robertson
authors.affiliation: Teva Pharmaceuticals, Frazer, PA, USA.
authors.forename: Mary
authors.initials: M
authors.lastname: Bond
mesh_terms: D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D000701:Analgesics, Opioid / Q000008:administration & dosage* / Q000009:adverse effects / Q000493:pharmacokinetics; D019540:Area Under Curve; D003692:Delayed-Action Preparations; D005260:Female; D006801:Humans; D006853:Hydrocodone / Q000008:administration & dosage* / Q000009:adverse effects / Q000493:pharmacokinetics; D007676:Kidney Failure, Chronic / Q000150:complications / Q000503:physiopathology; D008107:Liver Diseases / Q000150:complications* / Q000503:physiopathology; D008297:Male; D008875:Middle Aged; D051437:Renal Insufficiency / Q000150:complications* / Q000503:physiopathology; D012720:Severity of Illness Index; D013607:Tablets
chemical_list: D000701:Analgesics, Opioid; D003692:Delayed-Action Preparations; D013607:Tablets; D006853:Hydrocodone
keywords: ADME; cytochrome P450; extended release; hepatic clearance; hepatic impairment; hydrocodone; pharmacokinetics; renal excretion; renal impairment; systemic exposure