SOLVENT DRAG IN JEJUNAL ABSORPTION OF SALICYLIC ACID AND ANTIPYRINE OBTAINED BY IN SITU SINGLE-PASS RERFUSION METHOD IN RAT

  • HIRASAWA TOYOTO
    Department of Biopharmaceutics, Tokyo College of Pharmacy (Present Address) Research Laboratory, Taisho Pharmaceutical Co., Ltd.
  • MURAOKA TOSHIKO
    Department of Biopharmaceutics, Tokyo College of Pharmacy (Present Address) Research Laboratory, Taisho Pharmaceutical Co., Ltd.
  • KARINO AKIRA
    Department of Biopharmaceutics, Tokyo College of Pharmacy (Present Address) Research Laboratory, Taisho Pharmaceutical Co., Ltd.
  • HAYASHI MASAHIRO
    Department of Biopharmaceutics, Tokyo College of Pharmacy
  • AWAZU SHOJI
    Department of Biopharmaceutics, Tokyo College of Pharmacy

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説明

The in situ single-pass perfusion method in an individual rat was developed to discuss the solvent drag in drug intestinal absorption without the individual differences. In this method the apparent water influx (influx') was used as a measure of solvent drag in the same manner as the previous paper^<1)>. Consequently the sieving coefficients of salicylic acid and antipyrine in one rat are not significantly different from one but in the other are significantly smaller than one, resulting in 0.6-0.7 in average. And it was also shown that the reflection from the membrane in the solvent drag can be detected more precisely and efficiently by this method than the recirculating method in the previous paper. The D_2O absorption clearance (CL_<D_2O> was equal to net water flux as estimated theoretically when the D_2O concentration in lumen was equal to that in plasma, indicating that D_2O can be absorbed by water absorption even in the absence of the concentration gradient. Estimating the real water influx from the net water flux obtained under such condition, the minimal contribution ratio of the solvent drag to the total absorption clearance of salicylic acid and antipyrine was calculated to be approximately 12%.

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