An Examination of the Complex Pharmacological Properties of the Non-Selective Opioid Modulator Buprenorphine.

The goal of this review is to provide a recent examination of the pharmacodynamics as well as pharmacokinetics, misuse potential, toxicology, and prenatal consequences of buprenorphine. Buprenorphine is currently a Schedule III opioid in the US used for opioid-use disorder (OUD) and as an analgesic. Buprenorphine has high affinity for the mu-opioid receptor (MOR), delta (DOR), and kappa (KOR) and intermediate affinity for the nociceptin (NOR). Buprenorphine's active metabolite, norbuprenorphine, crosses the blood-brain barrier, is a potent metabolite that attenuates the analgesic effects of buprenorphine due to binding to NOR, and is responsible for the respiratory depressant effects. The area under the concentration curves are very similar for buprenorphine and norbuprenorphine, which indicates that it is important to consider this metabolite. Crowding sourcing has identified a buprenorphine street value (USD 3.95/mg), indicating some non-medical use. There have also been eleven-thousand reports involving buprenorphine and minors (age < 19) at US poison control centers. Prenatal exposure to clinically relevant dosages in rats produces reductions in myelin and increases in depression-like behavior. In conclusion, the pharmacology of this OUD pharmacotherapy including the consequences of prenatal buprenorphine exposure in humans and experimental animals should continue to be carefully evaluated.

Pronounced Declines in Meperidine in the US: Is the End Imminent?

Background: Once a widely used analgesic in the United States (US), meperidine offered an alternative opioid to other opioids as a pain reliever and was widely assumed to be safer with acute pancreatitis. However, within the last two decades meperidine, has gone from a frequently used drug to being used only when patients exhibit atypical reactions to opioids (e.g., morphine and hydromorphone), to being taken off the World Health Organization List of Essential Medications and receiving strong recommendations for overall avoidance. The aim of this study was to identify changes in meperidine distribution in the US, and regional disparities as reported to the Drug Enforcement Administration's Automation of Reports and Consolidated Orders System (DEA ARCOS) and Medicaid. Methods: Data related to meperidine distribution was obtained through ARCOS (2001−2021) and Medicaid public use files (2016−2021). Heat maps were used to visualize regional disparities in distribution by state. States outside a 95% confidence interval were statistically significant. Results: Meperidine distribution between 2001 and 2021 decreased by 97.4% (R = −0.97, p < 0.0001). There was a 34-fold state-level difference in meperidine distribution between Arkansas (16.8 mg/10 persons) and Connecticut (0.5 mg/10 persons) in 2020. Meperidine distribution in 2020 was elevated in Arkansas, Mississippi, and Alabama. In 2021, meperidine distribution was highest in Arkansas (16.7 mg/10 persons) and lowest in Connecticut (0.8 mg/10 persons). Total prescriptions of meperidine as reported by Medicaid decreased by 73.8% (R = −0.67, p = 0.045) between 2016 and 2021. Conclusion: We observed a decrease in the overall distribution of meperidine in the past two decades, with a similar recent decline in prescribing it to Medicaid enrollees. The shortage of some parenteral formulations is an important contributor to these declines, however, the most likely explanation for this global decline in use is related to an increased recognition of safety concerns related to important drug interactions and a neurotoxic metabolite. This data may reflect plans to phase out the use of this opioid, especially in the many situations where safer and more preferred opioids are available.