健康人におけるMenaquinone-4製剤投与後の血漿中Menaquinone-4の定量

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A sensitive method for menaquinone-4 (vitamin K_<2 (20)>, MQ-4) in the plasma by mass fragmentography was developed. In this method, micro-quantitative reductive acetylation was studied for the conversion of MQ-4 to volatile derivative. Then the concentration of MQ-4 in the plasma after the single administration of MQ-4 dosage forms (30-120 mg/man) to healthy male adult volunteers and the bioavailabilities of the dosage forms were examined. MQ-4 and phylloquinone (vitamin K_1,PQ) were extracted from the plasma to which PQ was added as an internal standard (IS). The extracts were dissolved in acetylating reagent (acetic anhydride-acetic acid-sodium acetate) and zinc dust was added, then refluxed for 1 h at 170℃ in a sealed glass tube. MQ-4 and PQ were converted to dihydromenaquinone-4 diacetate and dihydrophylloquinone diacetate, respectively and measured by mass fragmentography. The determination limit was 3 ng/ml plasma. MQ-4 given in syrup was absorbed more rapidly than that in capsule. The maximum plasma concentration (C_<max>) for the intramuscular administration of injection was lower than that for syrup, but then the concentration decreased very slowly. The plasma concentration after the intravenous administration of injection decreased apparently in a linear 3-compartment model. The area under concentration-time curve (AUC) after the oral administration of syrup or capsule was observed to be in proportion to the dose. The bioavailabilities of syrup and capsule were 38% and 29%, respectively.
社団法人日本薬学会の論文
1982-07-25

健康人におけるMenaquinone-4製剤投与後の血漿中Menaquinone-4の定量

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