RESUMEN
AIMS: To test the safety of new buprenorphine oral lyophilisate wafer ("bup-lyo") versus standard sub-lingual buprenorphine ("bup-SL"). DESIGN: Randomised (2:1) open-label study; opioid-dependent subjects; subsequent partial cross-over. SETTINGS: Specialised clinical trials facility and addictions treatment facility. PARTICIPANTS: Opioid-dependent subjects (n = 36) commencing buprenorphine maintenance (personalised dose-titration) including patients co-using alcohol, cocaine and benzodiazepines (below thresholds). MEASUREMENTS: Respiratory function (respiratory rate, pulse-oximetry); medication hold and dose adequacy; opiate withdrawal signs and symptoms; tablet disintegration times; treatment retention. Pharmacokinetics (PK) for plasma buprenorphine and norbuprenorphine (n = 11). FINDINGS: Oral lyophilised buprenorphine ("bup-lyo") completely dissolved within 2 min for 58 vs. 5% for "bup-SL." Dose titration resulted in similar maintenance dosing (10.8 vs. 9.6 mg). There were no significant between-group differences in opiate-withdrawal phenomena, craving, adequacy of "hold," respiratory function. No serious adverse events (AEs), nor "severe" AEs, although more AEs and Treatment-Emergent AEs with "bup-lyo" (mostly "mild"). PK found greater bioavailability of buprenorphine with "bup-lyo" (but not norbuprenorphine). CONCLUSIONS: Orally disintegrating buprenorphine oral lyophilisate wafer disintegrated rapidly. No increased respiratory depression was found and clinically no difference between medications was observed. PK found substantially increased bioavailability of buprenorphine (but not of nor-buprenorphine) with "bup-lyo" relative to "bup-SL." In supervised dosing contexts, rapidly disintegrating formulations may enable wider buprenorphine prescribing.
Asunto(s)
Buprenorfina/análogos & derivados , Buprenorfina/administración & dosificación , Tratamiento de Sustitución de Opiáceos/métodos , Trastornos Relacionados con Opioides/tratamiento farmacológico , Analgésicos Opioides/efectos adversos , Vías de Administración de Medicamentos , Femenino , Humanos , ComprimidosRESUMEN
INTRODUCTION AND AIMS: To establish if slow-release oral morphine (SROM) is an acceptable maintenance medication in heroin users currently being prescribed injectable diamorphine, who are intolerant to supplementary methadone. DESIGN AND METHODS: Case note review of interviews and medication details before and after change in medication in 12 treatment-resistant chronic heroin users attending a supervised injecting clinic twice a day for prescribed injectable diamorphine plus supplementary oral methadone to ensure 24 h stability. SROM was substituted for oral methadone by cross-titration. The patients' experiences of methadone treatment and expectations of SROM were recorded before the switch. Their responses to SROM and changes in injectable diamorphine requirements were recorded after a mean of 10 weeks' SROM treatment. RESULTS: The patients described a dislike and intolerance of methadone but had positive expectations of SROM which they believed would allow them to reduce their diamorphine dose. The mean stable methadone : SROM maintenance dose ratio was 1:7.5. After 10 weeks' SROM treatment, the average daily diamorphine dose reduced from 382 mg to 315 mg and patients reported fewer cravings and improved sleep and well-being. DISCUSSION AND CONCLUSIONS: Alternative forms of maintenance medication are required for patients who are intolerant to methadone. SROM is a valuable alternative which enabled some patients to reduce both their dose and number of injections of diamorphine. SROM treatment may therefore represent a route to stop injecting.