Switching Between Lyophilized And Sub-Lingual Buprenorphine Formulations In Opioid-Dependent Patients: Observations On Medication Transfer During A Safety And Pharmacokinetic Study

Background: A new lyophilized, rapid-disintegrating buprenorphine tablet ("bup-lyo") has been developed to potentially enhance adherence compared to conventional sublingual tablets ("bup-SL") but with a higher bioavailability of buprenorphine. Aim: To examine the pharmacokinetics, efficacy and safety of switching between formulations. Methods: Within a randomized trial of opioid-dependent subjects, one arm received "bup-lyo". After 2 weeks of treatment, all subjects switched back to standard sublingual "bup-SL" over 1-4 days in preparation for transfer back to their treating clinician. Observations were made of any change in clinical situation on transfer, or need for dose adjustment. Measurements included dose titration, treatment retention and within-subject comparisons of; pharmacokinetics (buprenorphine and norbuprenorphine), subjective scores of medication hold and dose adequacy, and safety assessments. Results: Subjects (N=23) were titrated to an effective and safe daily dose of "bup-lyo" (10.8 +/- 4.85 mg) (N=22) and then returned to the same dose of "bup-SL" (N=21). There had been no significant difference in dose, medication hold and dose adequacy between formulations on optimized treatment. Bloods were provided by 5 "bup-lyo" subjects for pharmacokinetic analysis: despite within-subject similar dosing, buprenorphine Cmax and AUC0-3hr (mean +/- SD) were significantly higher with "bup-lyo" than when switched to "bup-SL" (relative Cmax 185.8 +/- 88.2%, AUC0-3hr 169.8 +/- 62.0 %). However, for norbuprenorphine which is more associated with respiratory depression, the differences were not significant (relative Cmax 109.6 +/- 42.2%, AUC0-3hr 105.0 +/- 39.4 %). Adverse event incidence was slightly higher with "bup-lyo" but events were mild to moderate. Conclusion: Switching from "bup-lyo" to "bup-SL" did not require clinical adjustment of daily dose despite observed higher buprenorphine levels with "bup-lyo". The bioavailability of the metabolite norbuprenorphine, which is a more potent respiratory depressant than buprenorphine, was comparable between formulations. This may explain the absence of clinical difference in vital signs or other adverse events observed on switching formulations.