Triple dosing with high doses of buprenorphine: Withdrawal and plasma concentrations

In maintenance treatment for opiate addiction, buprenorphine can be administered less frequently than daily due to its long half-life.

To examine the plasma concentration of buprenorphine and norbuprenorphine for 72 hours after a dose of 72 mg and to objectively and subjectively evaluate the correlations between concentrations and withdrawal levels.

Patients in maintenance treatment with buprenorphine with a daily dose of 24 mg were given a triple dose of 72 mg (n = 9), in an outpatient setting. Blood samples were drawn, and withdrawal symptoms were evaluated objectively and subjectively every 24 hours over 72 hours. Urine and blood toxicology samples were obtained.

The triple dose was generally accepted well with low subjective and objective withdrawal scores. However, two patients aborted the study on day 3 and reported withdrawal symptoms. Benzodiazepine use was confirmed in one while the other likely used unauthorized buprenorphine.

Administration of buprenorphine in three times the daily dose seems acceptable, also in the higher daily maintenance doses (here, 24 mg) used in many clinical settings. Two patients did not tolerate the regimen but, partly due to the outpatient setting, the reasons why are unclear. Further research should be of interest as high buprenorphine doses are becoming more common clinically.