Single Dose IV Methadone for Post-Op Pain

The Adult Methadone study will be conducted at a single site, Duke Early Phase Research Unity (DEPRU), to enroll 24 participants. Participants will be treated/monitored overnight with Methadone hydrochloride IV (FDA approved and commercially available), with daily follow-up visits for 1 week total. The study aims to provide information on the disposition and clinical effects of intravenous methadone to update the drug label.

Inclusion criteria

• 18 to < 40 years of age at the time of enrollment
• Provide informed consent

Exclusion criteria

• History of cardiac dysfunction
• History of or current QTc prolongation, defined as > 470 ms in males and > 480 ms in females
• Known hypersensitivity to methadone hydrochloride or any other ingredient in the methadone hydrochloride injection
• Known acute bronchial asthma or hypercarbia (known history of known PaCO2 above 45 mm HG)
• Receipt of a serotonergic drug or buproprion within 7 days prior to study enrollment
• Receipt of benzodiazepines, muscle relaxants, or other opioids within 7 days prior to study enrollment
• Receipt of a moderate or strong CYP2B6 inhibitor or inducer - either prescription or non-prescription medications, herbals,34 or foods known to be metabolized by or affecting CYP2B6 - within 30 days prior to study enrollment

• CYP2B6 inhibitors include clopidogrel, prasugrel, thioTEPA, ticlopidine, voriconazole, macrolide antibiotics, azole-antifungal agents, fluconazole, Alstonia boonei, Mangifera indica, and Picralima nitida
• CYP2B6 inducers include artemisinin antimalarials, barbiturates, carbamazepine, cyclophosphamide, efavirenz, lopinavir, methimazole, nelfinavir, phenobarbital, phenytoin, primidone, rifampicin/rifampin, ritonavir, abacavir, amprenavir, nevirapine, telaprevir
• Receipt of zidovudine, desipramine, or other drugs that may increase serum concentration when combined with methadone within 30 days prior to study enrollment
• Known or suspected gastrointestinal obstruction, including paralytic ileus
• Significant respiratory depression (respiratory rate less than 8 breaths/min or oxygen saturation (SpO2) <95%)
• BMI ≥ 33 and BMI ≤ 17
• Known history of moderate-to-severe liver (Child Class B or C) or kidney disease (serum creatinine > 1.5)
• Known history of drug or alcohol addiction (prior or present addiction or treatment for addiction)
• Females who are pregnant or nursing