[First-pass effect of dauricine].
The first-pass effect of dauricine (Dau) was compared with that of lidocaine (Lid) by measuring the ventricular fibrillation threshold (VFT) and dauricine plasma concentration in rats or rabbits. After forelimb or mesenteric vein (imv) infusion of Dau at a rate of 1 mg.kg-1 x min-1 in rats, the VFT were 1.64-3.17 or 1.60-2.11 V, respectively. In the case of Lid at 2.5 mg.kg-1 x min-1, the VFT were 1.69-4.79 or 1.67-2.80 V, respectively, after ear vein (iev) or imv infusion of Dau at a rate of 0.5 mg.kg-1 x min-1 in rabbits, the VFT were 6.50-12.14 or 5.81-7.43 V, respectively. Plasma Dau concentration through iev infusion was significantly higher than that through imv route. As the dose of imv infusion increased, AUC of Dau showed a nonlinear increase. The results suggested that Dau showed a considerable first-pass effect, which was dose-dependent.
Gui
Y T
YT
Department of Clinical Pharmacology, Tongji Medical University, Hankou, China.
Du
Z H
ZH
Zeng
F D
FD
Hu
C J
CJ
D000470:Alkaloids; D000818:Animals; D000889:Anti-Arrhythmia Agents / Q000008:administration & dosage / Q000493:pharmacokinetics* / Q000627:therapeutic use; D044182:Benzylisoquinolines; D004423:Ear / Q000098:blood supply; D005260:Female; D005552:Forelimb / Q000098:blood supply; D007262:Infusions, Intravenous; D007546:Isoquinolines / Q000008:administration & dosage / Q000493:pharmacokinetics* / Q000627:therapeutic use; D008012:Lidocaine / Q000008:administration & dosage / Q000493:pharmacokinetics; D008099:Liver / Q000378:metabolism; D008297:Male; D008642:Mesenteric Veins; D011817:Rabbits; D051381:Rats; D017207:Rats, Sprague-Dawley; D044005:Tetrahydroisoquinolines; D014680:Veins; D014693:Ventricular Fibrillation / Q000517:prevention & control
D000470:Alkaloids; D000889:Anti-Arrhythmia Agents; D044182:Benzylisoquinolines; D007546:Isoquinolines; D044005:Tetrahydroisoquinolines; C035934:dauricine; D008012:Lidocaine