Study on the toxicokinetics and in vivo distribution of benzylpiperazine (BZP) and 1-(3-(trifluoromethyl)phenyl)piperazine (TFMPP) after single and combined administration in Wistar rats.

Benzylpiperazine (BZP) and 1-(3-(trifluoromethyl)phenyl)piperazine (TFMPP) are early‑appearing piperazine‑type new psychoactive substances (NPSs) frequently detected in ecstasy. Their combined use produces cardiovascular stimulation (hypertension and tachycardia) comparable to dextroamphetamine, yet data on their toxicokinetics and tissue distribution are scarce. We investigated the pharmacokinetics and tissue distribution of BZP and TFMPP after intraperitoneal injection (2 mg kg-1) in Wistar rats, both singly and in combination. Compared with single‑drug administration, combined dosing significantly altered t1/2 of BZP, mean residence time (MRT), and apparent volume of distribution (Vz/F), and reduced area under the curve (AUC) of TFMPP (p < 0.05). Apart from peak concentration (Cmax), the two compounds have similar toxicokinetic characteristics in some aspects. BZP and TFMPP were rapidly absorbed (Tmax 0.15-0.70 h). Elimination half‑lives were 0.36 h for BZP and 2.56 h for TFMPP. After a single dose, Cmax (173 ng/mL) of BZP was significantly lower than Cmax (284 ng/mL) of TFMPP. Twenty-four hours after administration, the tissue concentrations of BZP, whether given alone or in combination, ranked as follows: liver > kidney > lung > spleen > brain > heart. For TFMPP, the distribution pattern under combined administration was the same as that of BZP; however, when administered alone, its concentration in the brain was higher than that in the spleen. These findings indicate that co‑exposure to BZP and TFMPP can modify toxicokinetic behavior and tissue distribution, suggesting distinct poisoning dynamics from exposure to either compound alone.