Pharmacokinetic and Pharmacodynamic Correlations From 2 Studies Evaluating Abuse Potential of Hydrocodone Extended‐Release Tablets

Abstract

Pharmacokinetic (PK)/pharmacodynamic (PD) correlations were explored in 2 human abuse potential studies of orally and intranasally administered hydrocodone extended-release (ER) 45 mg in healthy, nondependent opioid users. In a crossover study design, subjects received intact hydrocodone ER, finely milled hydrocodone ER, and hydrocodone powder in solution in the oral study and finely milled hydrocodone ER, hydrocodone powder, and finely milled Zohydro® ER in the intranasal study. Spearman ρ and Pearson r values were calculated for PD (maximum effect [E ] for "at the moment" Drug Liking, Overall Drug Liking, and Take Drug Again visual analog scales [VAS]) vs PK (partial area under the concentration-time curve [AUC], maximum drug concentration [C ], time to C [T ], and abuse quotient [PK AQ; C /T ]) for all treatments. In the oral study, correlations were strongest between E of "at the moment" Drug Liking and PK parameters (C [ρ = 0.4446], PK AQ [ρ = 0.5179], T [ρ = 0.5093], and early systemic exposure [ρ = 0.4782]). For Overall Drug Liking and Take Drug Again VAS, ρ values for correlations with PK parameters ranged from 0.2620 to 0.3637. In the intranasal study, no clear correlations between PK and PD parameters were apparent.

Association of partial systemic exposure and abuse potential for opioid analgesics with abuse deterrence labeling claims supporting product-specific guidance

“… 5 Several studies reported that the abuse potential of opioids are correlated with the rate of rise of drug plasma concentration. [6] , [7] , [8] , [9] However, concerns remain for unraveling the relationships between PK exposure and clinical abuse potential scores and claims have been made such relationships may be complex and inconsistent considering the subjective nature of PD measures and the wide range of AD technologies. For instance, the Branded Industry Working Group compared chewing of oxycodone capsules under fed state (A) with chewing under fasting state (B) and noted that a higher C max value of oxycodone concentrations was observed under fed state (A) but a lower maximum visual analogue scale score for Take Drug Again was noted in subjects.…”