Systemic pharmacokinetic (PK) study of buprenorphine (B) in mild to moderate chronic hepatic impairment (CHI)

Purpose: Evaluation of possible effects of CHI on the systemic PK of B. Methods: Open-label, parallel-group, single-dose clinical study comparing the PK of I.V. B (0.3 mg over 10 minutes) in subjects with CHI (n=8 Childs Pugh A, n=4 Childs Pugh B) and age, weight and sex matched healthy controls (n=12). Plasma concentrations of B and norbuprenorphine (nor-B) were measured using HPLC-MS/MS assays. Systemic exposure was assessed using AUCt, AUC^∞, Cmax for B and AUCt, Cmax for nor-B. The 90% confidence intervals of log-transformed ratios were used to compare both groups. Safety evaluation included physical/lab results and AEs. Results: No difference in AUC^∞, t1/2, Vdss or CLtot for B was observed. Nor-B was formed in both groups, but plasma concentrations were highly variable and much less than B; AUCt for nor-B was not different between groups. Cmax was lower in CHI subjects for both B (50%) and nor-B (30%). CHI subjects had less nausea/vomiting than healthy subjects. Conclusions: No dosage adjustment of B is required in patients with mild to moderate CHI.