狂心発作寛解薬としての硝酸イソソルビドスプレー(E-100)の有用性-血圧降下作用と生物学的利用性からの検討-

概要

論文の詳細を見る
The usefulness of a spray (E-1000) of isosorbide dinitrate (ISDN), a new dosage form, has been determined and compared with that of its sublingual preparation (NR) in a cross-over study. Twelve healthy young male adults participated in this study. A total dose of 2.5 mg of E-1000 was sprayed over the both sides of the buccal mucous membrane, and a 5-mg tablet of NR was administered sublingually. The changes in blood pressure and heart rate, and the plasma levels and urinary excretions of ISDN and its two metabolites, were compared after administration. The plasma levels of unchanged ISDN and its metabolites isosorbide-2-mononitrate (2-ISMN) and isosorbide-5-mononitrate (5-ISMN) were determined by gas-liquidchromatography with an electron-capture detector. The area under the plasmaconcentration-time curve (AUC) for unchanged ISDN hardly differed between E-1000 (1300.8 ± 127.2 ng·Emin/ml) and NR (1260.4 ± 159.4 ng·Emin/ml), although the doseof the spray form was half of that of NR. Furthermore, the maximum plasmaconcentration (Cmax) of ISDN was about the same for both of the formulations (36.5 ±4.2 ng/ml for E-1000 and 35.7 ± 6.4 ng/ml for NR), and the time to reach the peakplasma level (Tmax) was 7.7 ± 0.9 min for E-1000, which was significantly shorter thanthe 18.2 ± 3.2 min taken with NR (P<0.01). These results indicated that the E-1000 dosage form offers a much higher bioavailability of ISDN than the sublingual form. On the other hand, the AUCs of 5-ISMN and of 2-ISMN were approximately proportional to the dose, and the percentage of urinary excretion of the two metabolites and their glucuronides were almost identical. Finally, an earlier manifestation of the blood pressure-lowering effect was elicited by E-1000 than by NR. Our results suggested that E-1000 rapidly exhibits an inhibitor effect on anginal attacks.

狂心発作寛解薬としての硝酸イソソルビドスプレー(E-100)の有用性-血圧降下作用と生物学的利用性からの検討-

スポンサーリンク

概要

著者

関連論文

スポンサーリンク