J. P. Jones, Y. Liu, P. J. Fudala, C. Heidbreder, A. F. Nasser; Reckitt Benckiser Pharmaceuticals, Inc., Richmond, VA

BACKGROUND: Suboxone® is a sublingual tablet or film formulation of buprenorphine/naloxone, which is currently used for the treatment of opioid dependence. To date, there are no published PK studies of sublingual buprenorphine (Bup) or naloxone (NLX) in subjects with varying degrees of HI.
METHODS: This study aimed to determine if mild to severe HI or HCV altered the PK of Bup or NLX using data from 43 subjects who received a single dose of Suboxone® 2.0/0.5 mg. PK parameters were calculated for Bup, NLX, and their primary metabolites using non-compartmental analysis. An analysis of covariance was performed to evaluate differences between PK parameters across HI groups.
RESULTS: In subjects with severe HI, approximately 2- to 3-fold increases in Bup Cmax, and AUC, and 11 to 15-fold increases in NLX Cmax and AUC were observed compared to healthy subjects. Subjects with moderate HI had increases of 8% and 64% in Bup Cmax and AUC0-last and approximately 3-fold increases in NLX Cmax and AUC compared to healthy subjects.
In subjects with mild HI, slight increases (20% to 25%) in Bup Cmax and AUC0-inf and similar NLX Cmax values were observed compared to healthy subjects. Small reductions of 20% to 30% were observed in naloxone AUC0-last and AUC0-inf, respectively, compared to healthy subjects. Subjects with HCV infection showed a small decrease (22%) in Bup AUC0-last, and 13% increase in Bup Cmax whereas similar NLX AUC0-last and a 26% increase in Cmax were observed compared to healthy subjects. Similar trends were observed with the major metabolites.
CONCLUSION: Severe and moderate HI altered significantly the PK of NLX and to a lesser extent the PK of Bup. Therefore, therapeutic risks vs. benefits as well as dose reduction and/or monitoring should be considered prior to the use of Bup/NLX product in these subjects.