Association Between Buprenorphine Dose and the Urine “Norbuprenorphine” to “Creatinine” Ratio: Revised
Authors: Furo Hiroko , Wiegand Timothy , Rani Meenakshi , Schwartz Diane G , Sullivan Ross W , Elkin Peter L 
Published: March 2023

Background: Utilizing a 1-year chart review as the data, Furo et al. conducted a research study on an association between buprenorphine dose and the urine “norbuprenorphine” to “creatinine” ratio and found significant differences in the ratio among 8-, 12-, and 16-mg/day groups with an analysis of variance (ANOVA) test. This study expands the data for a 2-year chart review and is intended to delineate an association between buprenorphine dose and the urine “norbuprenorphine” to “creatinine” ratio with a higher statistical power. Methods: This study performed a 2-year chart review of data for the patients living in a halfway house setting, where their drug administration was closely monitored. The patients were on buprenorphine prescribed at an outpatient clinic for opioid use disorder (OUD), and their buprenorphine prescription and dispensing information were confirmed by the New York Prescription Drug Monitoring Program (PDMP). Urine test results in the electronic health record (EHR) were reviewed, focusing on the “buprenorphine,” “norbuprenorphine,” and “creatinine” levels. The Kruskal–Wallis H and Mann–Whitney U tests were performed to examine an association between buprenorphine dose and the “norbuprenorphine” to “creatinine” ratio. Results: This study included 371 urine samples from 61 consecutive patients and analyzed the data in a manner similar to that described in the study by Furo et al. This study had similar findings with the following exceptions: (1) a mean buprenorphine dose of 11.0 ± 3.8 mg/day with a range of 2 to 20 mg/day; (2) exclusion of 6 urine samples with “creatinine” level <20 mg/dL; (3) minimum “norbuprenorphine” to “creatinine” ratios in the 8-, 12-, and 16-mg/day groups of 0.44 × 10−4 (n = 68), 0.1 × 10−4 (n = 133), and 1.37 × 10−4 (n = 82), respectively; however, after removing the 2 lowest outliers, the minimum “norbuprenorphine” to “creatinine” ratio in the 12-mg/day group was 1.6 × 10−4, similar to the findings in the previous study; and (4) a significant association between buprenorphine dose and the urine “norbuprenorphine” to “creatinine” ratios from the Kruskal-Wallis test ( P < .01). In addition, the median “norbuprenorphine” to “creatinine” ratio had a strong association with buprenorphine dose, and this association could be formulated as: [y = 2.266 ln( x) + 0.8211]. In other words, the median ratios in 8-, 12-, and 16-mg/day groups were 5.53 × 10−4, 6.45 × 10−4, and 7.10 × 10−4, respectively. Therefore, any of the following features should alert providers to further investigate patient treatment compliance: (1) inappropriate substance(s) in urine sample; (2) “creatinine” level <20 mg/dL; (3) “buprenorphine” to “norbuprenorphine” ratio >50:1; (4) buprenorphine dose >24 mg/day; or (5) “norbuprenorphine” to “creatinine” ratios <0.5 × 10−4 in patients who are on 8 mg/day or <1.5 × 10−4 in patients who are on 12 mg/day or more. Conclusion: The results of the present study confirmed those of the previous study regarding an association between buprenorphine dose and the “norbuprenorphine” to “creatinine” ratio, using an expanded data set. Additionally, this study delineated a clearer relationship, focusing on the median “norbuprenorphine” to “creatinine” ratios in different buprenorphine dose groups. These results could help providers interpret urine test results more accurately and apply them to outpatient opioid treatment programs for optimal treatment outcomes.