Glecaprevir/Pibrentasvir + Buprenorphine/Naloxone = Unknown or no reaction

Study Design

In a 2-period, single-center, open-label, phase I study, the pharmacokinetic (PK) drug interaction potential was assessed between ABT-493 + ABT-530 and methadone. Healthy adults subjects received individualized regimens of methadone (n=11) once daily on Days 1-9 in Period 1. In Period 2, subjects received ABT-493 (300 mg daily) + ABT-530 (120 mg daily) together with methadone for 7 days, followed by methadone alone on Days 8-10.The maintenance therapy dose for methadone ranged from 22 to 120 mg.For assessment of pharmacokinetics (PK) of R- and S- methadone, serial blood samples were collected on Day 9 of Period 1 and Day 7 of Period 2. For assessment of PK of ABT-493 and ABT-530, serial blood samples were collected on Day 7 of Period 2.

Study Results

Coadministration of methadone with multiple doses of ABT-493 (300 mg daily) plus ABT-530 (120 mg daily) resulted in slightly increased PK parameters of both buprenorphine and norbuprenorphine.The geometric mean ratios (GMRs; ABT-493/ABT-530 + BUP/NAL/ BUP/NAL) [90% CIs] of buprenorphine were: 1.08 [0.97, 1.19] for Cmax, 1.17 [1.08, 1.27] for AUC24, 1.24 [1.09, 1.40] for C24The geometric mean ratios (GMRs; ABT-493/ABT-530 + methadone / methadone) [90% CIs] of norbuprenorphine were: 1.25 [1.17, 1.34] for Cmax, 1.30 [1.19, 1.42] for AUC24, 1.21 [1.06, 1.39] for C24ABT-493/ ABT-530 minimally affected PKs of naloxone. GMRs (ABT-493/ ABT-530 + BUP/NAL / BUP/NAL) [90% CIs] of Cmax and AUC for naloxone were 0.88 [0.74, 1.06] and 1.07 [0.90, 1.28], respectively.Although the effect of BUP/NAL on ABT-493 and ABT-530 was not evaluated in this study, the investigators reported that their exposures were similar to those reported in other studies in healthy subjects.Subjects experienced mild adverse events. Common adverse events were abdominal pain, constipation, and headache.However, no changes in pupillary response, SOWS and DDQ were observed when ABT-493 and ABT-530 were added to BUP/NAL therapy.

Study Conclusions

References

Kosloski MP, S Dutta, W Zhao, et al. Absence of significant drug-drug interactions between next generation direct acting antivirals abt-493 and abt-530 and methadone or buprenorphine/naloxone in subjects on opioid maintenance therapy. 66th Annual Meeting Of The American Association For The Study Of Liver Diseases (aasld). San Francisco, CA. ; 2015.