A PHARMACOKINETIC STUDY WITH THE HIGH-DOSE ANTICANCER AGENT MENADIONE IN RABBITS

✍ Scribed by Oliver Yoa-Pu Hu; Chih-Yuan Wu; Win-Kai Chan; Felicia Y.-H. Wu; Jacqueline Whang-Peng

• Publisher: John Wiley and Sons
• Year: 1996
• Tongue: English
• Weight: 413 KB
• Volume: 17
• Category: Article
• ISSN: 0142-2782
• DOI: 10.1002/(sici)1099-081x(199608)17:6<493::aid-bdd972>3.0.co;2-6

✦ Synopsis

The aim of this investigation was to assess the pharmacokinetic properties of high-dose menadione (VK,), as an anticancer agent, in plasma and red blood cells (RBCs) in rabbits. An extremely high dose of 75 mg menadiol sodium diphosphate (Synkayvite) was intravenously injected. HPLC analysis was applied to measure the major metabolite, menadione, VK,. The kinetic properties of VK3 in both plasma and red blood cells showed a short elimination half-life, high clearance, and large volume of distribution in plasma and RBCs. The mean elimination tl,* values of menadione in plasma and in RBCs were 27.17+ 10.49min and 35.22+ 1142min, respectively. The plasma clearance (CLIF) of VK, was 0.822 & 0.254 L min-I. The systemic clearance in RBCs was 0.407 & 0.152 L minl . The apparent volume of distribution (Vd/F) in plasma was 30.833+12.835L and that in RBCs 20.488+9.401L. The plasma AUC was 32-453 + 9.785 pg min mL-and that of RBCs 67.2 19 24.449 pg min mL-'. Menadiol was rapidly biotransformed to menadione in blood. The formation rate constant (k') of menadione in plasma was 0.589 & 0.246 min-I, and that of RBCs 1.520 _+ 1.345 min-I. Through this study the estimated menadione dosage needed to maintain a plasma level of 1 pgmL-' for anticancer purposes was 19.7mgkg-' every hour.