Abstract: AIM: To study the chronological pharmacokinetic differences of melatonin (MEL) in non-dipper spontaneously hypertensive rats (SHR).  METHODS: The HPLC detection method of MEL was established, and the specificity, precision, recovery rate and stability of the method were examined. Twelve male SD rats were divided into two groups, and a single dose of MEL (20 mg/kg) was given intragastrically at either 08∶00 or 20∶00, respectively. Plasma samples were collected at 0, 5, 10, 15, 20, 30, 40, 60, 90, 120, 240, 360 min after drug administration, and the plasma MEL concentration was determined by fluorescence HPLC. RESULTS: The specificity, precision, recovery rate and stability of the MEL detection method established in this study were in line with the requirements of the biological analysis method guidelines, proving that the method was mature and reliable. After MEL was administered at 08∶00, the Tmax could be reached in about 19 min. However, in 20∶00 group rats, it took about 32 min to reach Tmax (P<0.01). Cmax, AUC, T1/2 in 08∶00 group rats were significantly higher than that of rats in 20∶00 group (P<0.05, P<0.01). The pharmacokinetic parameters CL in the 20∶00 group rats were significantly higher than 08∶00 group rats (P<0.05). CONCLUSION: Medication at different times of day and night has a certain degree of influence on the pharmacokinetics of MEL in non-dipper SHR rats. From the perspective of pharmacokinetics, the mechanism of MEL restoring blood pressure rhythm is partly elucidated, which provides a theoretical basis for the rational use of drugs in clinic.

Key words: melatonin, pharmacokinetics, circadian rhythm, non-dipper hypertension