The Effect of Circadian Rhythm on the Gentamicin Pharmacokinetics in Rabbits

가토에서 생체리듬이 겐타마이신의 약물동태에 미치는 영향

The effect of circadian rhythm on gentamicin pharmacokinetics was studied in rabbits who took a single intravenous 2 mg/kg dose of gentamicin at 09:00 in the morning (a.m.) and 22:00 in the evening (p.m.). A significant circadian rhythm of pharmacokinetic parameters as a function of time of day was noted in rabbits, showing lower total body clearance $CL_t$ and higher serum area under the curve (AUC) when given in the evening. The half-life $t_{1/2}$ was shorter in the morning $(3.88\pm0.62h)$ when compared to the evening $(4.76\pm0.75\;h)$. The AUC was greater in the evening $(25.92\pm3.49\;{\mu}g/ml{\cdot}hr)$ than that in the morning $(22.42\pm3.42\;{\mu}g/ml{\cdot}hr)$, most likely because the CLt was significantly higher when gentamicin was given in the morning $(0.18\pm0.28\;ml/hr)$ versus in the evening $(0.15\pm0.26\;ml/hr)$. The $t_{1/2}$ of gentamicin in the evening was increased significantly(p<0.05) compared to those of gentamicin in the morning. It is reasonable to consider individual circadian rhythm for effective dosage regimen of gentamicin in clinical chronotherapeutics.