Concentration-Response Model of Immediate Release Oxycodone Drug Liking by Different Routes of Abuse

Objective To understand the correlation between oxycodone concentration and drug liking response for immediate-release formulations as they relate to different doses and different routes of administration following manipulation involved in opioid misuse and nontherapeutic use. Methods Concentration-response and noncompartmental analyses of drug liking and plasma oxycodone data from Category 3 human abuse potential studies (n = 15-29 per study) were conducted, using Phoenix 6.0 software. Time to onset of a set threshold of subjective effects (T-onset) and offset of subjective effects (T-offset) were estimated based on a baseline pharmacodynamic response set at 50 on a bipolar Drug Liking visual analog scale of 0-100 and the threshold for drug liking set at >= 65, based on study qualification criteria. Partial Area Under the Concentration (AUC(Tonset-Toffset)) and Effect (AUE(Tonset-Toffset)) profiles were calculated and their correlation with individual partial AUE vs partial AUC was assessed. Results The oxycodone concentration-response (drug liking) was best described by a sigmoidal-effect E-max model (S-shaped). Using a defined threshold, drug liking was closely associated with the rate of rise in concentration and the onset of action for oxycodone administered via oral or intranasal route. Partial AUC(Tonset-Toffset) and AUE(Tonset-Toffset) showed a strong linear correlation. Conclusions Results indicate that oxycodone concentration-response and duration of drug liking following manipulation via different routes of administration may be an approach for further exploring drug liking effects of opioids.