Oral Abuse Potential of Benzhydrocodone, a Novel Prodrug of Hydrocodone

Hydrocodone bitartrate (HB) and acetaminophen (APAP) combination products are known to be abused via oral, intranasal, and intravenous self-administration. Benzhydrocodone HCl (KP201) is a prodrug of hydrocodone with limited bioavailability when taken intranasally or intravenously, or taken orally at supratherapeutic doses. This study assessed the abuse liability, relative bioavailability, and safety of KP201/APAP, compared with that of HB/APAP (Norco®), when administered at supratherapeutic oral doses to non-dependent, recreational opioid users. Both KP201/APAP and HB/APAP were generally well tolerated and had similar Drug Liking scores, but KP201/APAP displayed lower peak and cumulative systemic exposure to hydrocodone at high and mid oral doses.