Pharmacokinetics of Acetaminophen in the Hypothalamus of Rats Based on in vivo Microdialysis

Abstract

To explore the studying method for pharmacokinetics in the target site of drugs, the pharmacokinetic process of acetaminophen in the hypothalamus of rats was investigated. Male Sprague-Dawleyrats were anaesthetized and secured in a stereotaxic frame. A microdialysis probe was implanted into the hypothalamus and perfused with artificial cerebrospinal fluid at a flow rate of 2 μL/min. Adaptation for 1 h, rats were administrated with acetaminophen (150 mg/kg, i.p.) and microdialysates were collected continuously at 12-min intervals for 6 h. The acetaminophen concentrations in microdialysates were determined by HPLC-Ultraviolet detection (HPLC-UV), and the concentration-time profile and pharmacokinetic parameters of acetaminophen were calculated by DAS software. The results showed that the concentration-time curve of acetaminophen in the hypothalamus of rats was fitted to a one-compartment open model. The main pharmacokinetic parameters t1/2, Tmax, Cmax and AUCinf were (1.95 ± 0.59) h, (1.26 ± 0.22) h, (11.39 ± 2.17) μg/mL and (58.04 ± 18.39) μg·h/mL, respectively. In conclusion, by means of in vivo microdialysis approach, the pharmacokinetic process of acetaminophen in the hypothalamus of rats is investigated and an experimental method for studying pharmacokinetics of drugs in the target site is established, which is simple, feasible and reliable.