Pharmacokinetic and Pharmacodynamic Correlations From 2 Studies Evaluating Abuse Potential of Hydrocodone...

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 ρ² and Pearson r² values were calculated for PD (maximum effect [E_max ] 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_max ], time to C_max [T_max ], and abuse quotient [PK AQ; C_max /T_max ]) for all treatments. In the oral study, correlations were strongest between E_max of "at the moment" Drug Liking and PK parameters (C_max [ρ²  = 0.4446], PK AQ [ρ²  = 0.5179], T_max [ρ²  = 0.5093], and early systemic exposure [ρ²  = 0.4782]). For Overall Drug Liking and Take Drug Again VAS, ρ² 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.