Comparative pharmacokinetic and intracerebral distribution of MDMB‐4F‐BICA in mice following inhalation (‘vapor’) and subcutaneous injection

Abstract

MDMB‐4F‐BICA, also known as 4F‐MDMB‐BICA, is a new psychoactive substance that emerged in 2020. It is often illegally added to electronic cigarette oil for inhalation abuse, leading to serious adverse symptoms and even death. There are significant differences in pharmacokinetics between inhalation administration and conventional drug delivery methods. Inhalation administration can pass through the blood-brain barrier to enter the brain directly. However, the specific distribution of the drug in the brain following inhalation has not been well investigated. In order to scientifically compare the absorption and distribution of MDMB‐4F‐BICA after two administration methods (inhalation and subcutaneous injection), this study analyzed the drug concentration in mice blood and brain by LC-MS/MS after systemic exposure inhalation in the form of electronic cigarettes. The aim was to conduct the pharmacokinetics study of MDMB‐4F‐BICA after inhalation(‘vapor’) administration. Pharmacokinetics and distribution of the compound revealed that the maximum concentrations in blood of this compound were reached at 0.5 min and 15 min, respectively, and the concentration in the brain reached the maximum at the same time after two modes of administration. The drug concentration in the brain was higher than that of subcutaneous injection, and the drug remained at a low concentration in the brain for a long period (20 ng/g brain tissue) with a significant distribution in several olfactory primary cortex brain regions. Taken together, the pharmacokinetics of the synthetic cannabinoid MDMB‐4F‐BICA after single systemic exposure inhalation were investigated for the first time in this study. A basis for subsequent evaluation research of inhalation-related harmfulness is provided by comparing the distribution of drugs in the brain after the two administration modes.