Circadian variations in the pharmacokinetics of bucinnazine in rats

ABSTRACT

Circadian rhythms play crucial roles in the action and pharmacokinetics of a drug. The processes from drug absorption to excretion, which participate in pharmacokinetic steps, are circadian time-dependent. Our previous study has demonstrated that the analgesic effect of bucinnazine, an anesthetic analgesic drug, revealed significant circadian variation. In the current study, we aimed to investigate the effect of different administration time on the pharmacokinetic process of bucinnazine in rats. Male Sprague Dawley rats were randomly divided into 9:00 am and 9:00 pm groups. Blood samples (0.4 ml) were, respectively, collected at 0, 0.033, 0.083, 0.17, 0.33, 0.67, 1, 1.5, 2, 3, 4, 6, and 8 h after intraperitoneal injection of 20 mg/kg bucinnazine and determined using the established liquid chromatography-tandem mass spectrometry method. DAS 2.0 was used to calculate the pharmacokinetic parameters. The pharmacokinetics of bucinnazine exhibited significant circadian-time dependence. AUC and C_max of bucinnazine increased significantly at 9:00 am compared with that at 9:00 pm (P < 0.05), while T_max was significantly decreased at 9:00 am than at 9:00 pm (P < 0.05). Pharmacokinetic processes of bucinnazine significantly varied along with administration time, indicating that attention should be paid to the time in clinical practice to improve analgesic effects and to decrease adverse reactions.

KEYWORDS:

• Bucinnazine
• pharmacokinetics
• circadian rhythm
• administration time
• liquid chromatography-tandem mass spectrometry

Disclosure statement

No potential conflict of interest was reported by the authors.

Additional information

Funding

This work was supported by Grants No. 81603202 from the National Natural Science Foundation of China.