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Terumichi Nakagawa - One of the best experts on this subject based on the ideXlab platform.

  • effect of pentobarbital anaesthesia on intestinal absorption and hepatic first pass metabolism of oxacillin in rats evaluated by portal systemic Concentration Difference
    Journal of Pharmacy and Pharmacology, 2010
    Co-Authors: Shinya Ueda, Kiyoshi Yamaoka, Terumichi Nakagawa
    Abstract:

    The effects of anaesthesia on intestinal drug absorption and hepatic first-pass metabolism in rats were investigated by observing the Difference in the drug Concentration between portal and systemic bloods. Oxacillin and pentobarbital were selected as a model drug and as an anaesthetic, respectively. Rats were divided into a conscious control group and an anaesthetized group. All rats were cannulated simultaneously in the portal vein and in the femoral artery, and oxacillin was orally administered after its intra-arterial injection (double dosing). For the anaesthetized group, pentobarbital was intrasubcutaneously administered twice, first before intra-arterial injection and again before oral administration of oxacillin. The arterial blood alone was sampled from the cannula in the femoral artery before oral administration, whereas the arterial and portal bloods were simultaneously sampled from both cannulated sites after oral administration. Oxacillin Concentrations in plasma were assayed by HPLC. The anaesthesia increased the absolute bioavailability (F), the mean absorption time (MAT) and the hepatic recovery ratio (FH), but caused little change in the local absorption ratio into the portal system (Fa) and the total clearance (CL). The hepatic clearance (CLH) was significantly decreased, resulting in an apparent small change in CL—CLH which is considered to be renal clearance. By this method, it was shown directly that an increase in F due to pentobarbital anaesthesia was attributable to the significant increase in FH. It is expected that the method is useful not only to evaluate the effect of anaesthesia on the first-pass effect, but also to assess the effect of co-administration of drugs on first-pass metabolism.

  • Effect of coadministered uridine on intestinal first-pass metabolism of 5'-deoxy-5-fluorouridine in conscious rats--an evaluation by method of portal-systemic Concentration Difference.
    Pharmaceutical research, 1998
    Co-Authors: Yoneichi Sawai, Kiyoshi Yamaoka, Terumichi Nakagawa
    Abstract:

    Purpose. The effect of uridine (UR) coadministration on the intestinal metabolism from 5′-deoxy-5-fluorouridine (5′-DFUR) to 5-fluorouracil (5-FU) was evaluated by a method of Concentration Difference between portal and systemic bloods in conscious rats (PS method).

  • moment analysis of intestinal first pass metabolism by portal systemic Concentration Difference in single conscious rat using 5 deoxy 5 fluorouridine and 5 fluorouracil as model drug system
    Journal of Pharmaceutical Sciences, 1997
    Co-Authors: Yoneichi Sawai, Kiyoshi Yamaoka, Arisa Takemura, Terumichi Nakagawa
    Abstract:

    Intestinal first-pass metabolism was evaluated in a single conscious rat based on a Difference in Concentrations of parent drug and its metabolite between the portal and systemic bloods (P–S Difference method). 5′-Deoxy-5-fluorouridine (5′-DFUR) and 5-fluorouracil (5-FU) were selected as model drug (prodrug of 5-Fu) and metabolite pair. The portal vein and the femoral artery of the rat were cannulated so blood samples could be obtained simultaneously from the two sites. 5′-DFUR (100 mg/kg) was administered intraarterially or orally. Concentrations of 5′-DFUR and 5-FU in the portal and arterial samples were assayed by HPLC. The Concentration–time profiles of 5′-DFUR and 5-FU were analyzed by local moment analysis. The extent of systemic bioavailability (F) of 5′-DFUR was estimated to be 75.8%. After oral administration, the local absorption ratio (Fa) and the mean local absorption time t¯a of 5′-DFUR were estimated to be 65.8 ± 7.3% of dose and 74.0 ± 21.7 min, respectively. The Fa value was close to F, which suggests that the metabolic conversion from 5′-DFUR to 5-FU is not extensive in the liver. The mean absorption time (MAT), calculated to be 76.3 min, almost coincided with t¯a, which suggests that the mean hepatic transit time is negligible in this experimental scale. The local absorption ratio of metabolite (Fam) was 6.8 ± 1.7% of orally administered 5′-DFUR, which means that ~ 7% of 5′-DFUR arrived as 5-FU at the portal system. The mean local absorption time t¯am of 5-FU was estimated to be 75.5 min, which is close to that (74.0 min) of 5′-DFUR. Local moment analysis based on P–S Difference enabled simultaneous estimation of the local absorption kinetics of a parent compound and the intestinal generation of metabolites by separating the intestinal first-pass metabolism of a drug from the subsequent disposition through the liver and in the systemic circulation.

  • local absorption kinetics into the portal system using the portal venous Concentration Difference after an oral dose of diclofenac in the awakening rat accelerative effect of bile on intestinal absorption of diclofenac
    Drug Metabolism and Disposition, 1996
    Co-Authors: Kenji Tabata, Kiyoshi Yamaoka, Takako Fukuyama, Terumichi Nakagawa
    Abstract:

    The local absorption kinetics from the intestinal tract into the portal system was evaluated using the portal-venous Concentration Difference (P-V Difference) after oral administration of diclofenac in conscious rats. The local absorption ratio (Fa), mean local absorption time (ta), and relative variance (sigma 2/ta2) from the intestinal tract into the portal system were estimated by simultaneously measuring the portal and venous Concentrations, using diclofenac as a model drug. The effect of bile on diclofenac intestinal absorption was also investigated. The awakening rats simultaneously cannulated into the jugular and portal veins were divided into group A with intact enterohepatic circulation (EHC) and into another group with bile-duct cannulation to block EHC. The rats in the latter group were further divided into group B without the bile supply to the intestinal tract and into group C with the bile supply from the other rat. After oral administration of diclofenac to rats in groups A, B, and C, the portal and venous Concentrations of diclofenac in each rat were simultaneously monitored by HPLC method at proper time intervals. The absorption time profile of diclofenac into the portal system was directly predicted from P-V Difference. Plasma Concentrations of diclofenac in the portal vein were constantly higher than those in the jugular vein after the oral administration. It was demonstrated that P-V Difference was caused by absorption from the intestinal tract into the portal system. Fa in groups A, B, and C were estimated to be 91.5% for 8 hr, 33.8% for 3 hr, and 57.8% for 3 hr, respectively. ta in groups A, B, and C were estimated to be 2.26 hr, 0.65 hr, and 0.96 hr, respectively. sigma 2/ta2 in groups A, B, and C were 1.31, 0.48, and 0.55, respectively. Fa and ta of diclofenac extensively increased in the presence of the bile in the intestinal tract, whereas sigma 2/ta2 was unaffected by the bile. The mean absorption time (MAT) almost agreed with ta, which demonstrates that the mean transit time through the liver (tH) is negligible in MAT(= ta+tH).

Kiyoshi Yamaoka - One of the best experts on this subject based on the ideXlab platform.

  • effect of pentobarbital anaesthesia on intestinal absorption and hepatic first pass metabolism of oxacillin in rats evaluated by portal systemic Concentration Difference
    Journal of Pharmacy and Pharmacology, 2010
    Co-Authors: Shinya Ueda, Kiyoshi Yamaoka, Terumichi Nakagawa
    Abstract:

    The effects of anaesthesia on intestinal drug absorption and hepatic first-pass metabolism in rats were investigated by observing the Difference in the drug Concentration between portal and systemic bloods. Oxacillin and pentobarbital were selected as a model drug and as an anaesthetic, respectively. Rats were divided into a conscious control group and an anaesthetized group. All rats were cannulated simultaneously in the portal vein and in the femoral artery, and oxacillin was orally administered after its intra-arterial injection (double dosing). For the anaesthetized group, pentobarbital was intrasubcutaneously administered twice, first before intra-arterial injection and again before oral administration of oxacillin. The arterial blood alone was sampled from the cannula in the femoral artery before oral administration, whereas the arterial and portal bloods were simultaneously sampled from both cannulated sites after oral administration. Oxacillin Concentrations in plasma were assayed by HPLC. The anaesthesia increased the absolute bioavailability (F), the mean absorption time (MAT) and the hepatic recovery ratio (FH), but caused little change in the local absorption ratio into the portal system (Fa) and the total clearance (CL). The hepatic clearance (CLH) was significantly decreased, resulting in an apparent small change in CL—CLH which is considered to be renal clearance. By this method, it was shown directly that an increase in F due to pentobarbital anaesthesia was attributable to the significant increase in FH. It is expected that the method is useful not only to evaluate the effect of anaesthesia on the first-pass effect, but also to assess the effect of co-administration of drugs on first-pass metabolism.

  • Effect of coadministered uridine on intestinal first-pass metabolism of 5'-deoxy-5-fluorouridine in conscious rats--an evaluation by method of portal-systemic Concentration Difference.
    Pharmaceutical research, 1998
    Co-Authors: Yoneichi Sawai, Kiyoshi Yamaoka, Terumichi Nakagawa
    Abstract:

    Purpose. The effect of uridine (UR) coadministration on the intestinal metabolism from 5′-deoxy-5-fluorouridine (5′-DFUR) to 5-fluorouracil (5-FU) was evaluated by a method of Concentration Difference between portal and systemic bloods in conscious rats (PS method).

  • moment analysis of intestinal first pass metabolism by portal systemic Concentration Difference in single conscious rat using 5 deoxy 5 fluorouridine and 5 fluorouracil as model drug system
    Journal of Pharmaceutical Sciences, 1997
    Co-Authors: Yoneichi Sawai, Kiyoshi Yamaoka, Arisa Takemura, Terumichi Nakagawa
    Abstract:

    Intestinal first-pass metabolism was evaluated in a single conscious rat based on a Difference in Concentrations of parent drug and its metabolite between the portal and systemic bloods (P–S Difference method). 5′-Deoxy-5-fluorouridine (5′-DFUR) and 5-fluorouracil (5-FU) were selected as model drug (prodrug of 5-Fu) and metabolite pair. The portal vein and the femoral artery of the rat were cannulated so blood samples could be obtained simultaneously from the two sites. 5′-DFUR (100 mg/kg) was administered intraarterially or orally. Concentrations of 5′-DFUR and 5-FU in the portal and arterial samples were assayed by HPLC. The Concentration–time profiles of 5′-DFUR and 5-FU were analyzed by local moment analysis. The extent of systemic bioavailability (F) of 5′-DFUR was estimated to be 75.8%. After oral administration, the local absorption ratio (Fa) and the mean local absorption time t¯a of 5′-DFUR were estimated to be 65.8 ± 7.3% of dose and 74.0 ± 21.7 min, respectively. The Fa value was close to F, which suggests that the metabolic conversion from 5′-DFUR to 5-FU is not extensive in the liver. The mean absorption time (MAT), calculated to be 76.3 min, almost coincided with t¯a, which suggests that the mean hepatic transit time is negligible in this experimental scale. The local absorption ratio of metabolite (Fam) was 6.8 ± 1.7% of orally administered 5′-DFUR, which means that ~ 7% of 5′-DFUR arrived as 5-FU at the portal system. The mean local absorption time t¯am of 5-FU was estimated to be 75.5 min, which is close to that (74.0 min) of 5′-DFUR. Local moment analysis based on P–S Difference enabled simultaneous estimation of the local absorption kinetics of a parent compound and the intestinal generation of metabolites by separating the intestinal first-pass metabolism of a drug from the subsequent disposition through the liver and in the systemic circulation.

  • local absorption kinetics into the portal system using the portal venous Concentration Difference after an oral dose of diclofenac in the awakening rat accelerative effect of bile on intestinal absorption of diclofenac
    Drug Metabolism and Disposition, 1996
    Co-Authors: Kenji Tabata, Kiyoshi Yamaoka, Takako Fukuyama, Terumichi Nakagawa
    Abstract:

    The local absorption kinetics from the intestinal tract into the portal system was evaluated using the portal-venous Concentration Difference (P-V Difference) after oral administration of diclofenac in conscious rats. The local absorption ratio (Fa), mean local absorption time (ta), and relative variance (sigma 2/ta2) from the intestinal tract into the portal system were estimated by simultaneously measuring the portal and venous Concentrations, using diclofenac as a model drug. The effect of bile on diclofenac intestinal absorption was also investigated. The awakening rats simultaneously cannulated into the jugular and portal veins were divided into group A with intact enterohepatic circulation (EHC) and into another group with bile-duct cannulation to block EHC. The rats in the latter group were further divided into group B without the bile supply to the intestinal tract and into group C with the bile supply from the other rat. After oral administration of diclofenac to rats in groups A, B, and C, the portal and venous Concentrations of diclofenac in each rat were simultaneously monitored by HPLC method at proper time intervals. The absorption time profile of diclofenac into the portal system was directly predicted from P-V Difference. Plasma Concentrations of diclofenac in the portal vein were constantly higher than those in the jugular vein after the oral administration. It was demonstrated that P-V Difference was caused by absorption from the intestinal tract into the portal system. Fa in groups A, B, and C were estimated to be 91.5% for 8 hr, 33.8% for 3 hr, and 57.8% for 3 hr, respectively. ta in groups A, B, and C were estimated to be 2.26 hr, 0.65 hr, and 0.96 hr, respectively. sigma 2/ta2 in groups A, B, and C were 1.31, 0.48, and 0.55, respectively. Fa and ta of diclofenac extensively increased in the presence of the bile in the intestinal tract, whereas sigma 2/ta2 was unaffected by the bile. The mean absorption time (MAT) almost agreed with ta, which demonstrates that the mean transit time through the liver (tH) is negligible in MAT(= ta+tH).

Yoneichi Sawai - One of the best experts on this subject based on the ideXlab platform.

  • Effect of coadministered uridine on intestinal first-pass metabolism of 5'-deoxy-5-fluorouridine in conscious rats--an evaluation by method of portal-systemic Concentration Difference.
    Pharmaceutical research, 1998
    Co-Authors: Yoneichi Sawai, Kiyoshi Yamaoka, Terumichi Nakagawa
    Abstract:

    Purpose. The effect of uridine (UR) coadministration on the intestinal metabolism from 5′-deoxy-5-fluorouridine (5′-DFUR) to 5-fluorouracil (5-FU) was evaluated by a method of Concentration Difference between portal and systemic bloods in conscious rats (PS method).

  • moment analysis of intestinal first pass metabolism by portal systemic Concentration Difference in single conscious rat using 5 deoxy 5 fluorouridine and 5 fluorouracil as model drug system
    Journal of Pharmaceutical Sciences, 1997
    Co-Authors: Yoneichi Sawai, Kiyoshi Yamaoka, Arisa Takemura, Terumichi Nakagawa
    Abstract:

    Intestinal first-pass metabolism was evaluated in a single conscious rat based on a Difference in Concentrations of parent drug and its metabolite between the portal and systemic bloods (P–S Difference method). 5′-Deoxy-5-fluorouridine (5′-DFUR) and 5-fluorouracil (5-FU) were selected as model drug (prodrug of 5-Fu) and metabolite pair. The portal vein and the femoral artery of the rat were cannulated so blood samples could be obtained simultaneously from the two sites. 5′-DFUR (100 mg/kg) was administered intraarterially or orally. Concentrations of 5′-DFUR and 5-FU in the portal and arterial samples were assayed by HPLC. The Concentration–time profiles of 5′-DFUR and 5-FU were analyzed by local moment analysis. The extent of systemic bioavailability (F) of 5′-DFUR was estimated to be 75.8%. After oral administration, the local absorption ratio (Fa) and the mean local absorption time t¯a of 5′-DFUR were estimated to be 65.8 ± 7.3% of dose and 74.0 ± 21.7 min, respectively. The Fa value was close to F, which suggests that the metabolic conversion from 5′-DFUR to 5-FU is not extensive in the liver. The mean absorption time (MAT), calculated to be 76.3 min, almost coincided with t¯a, which suggests that the mean hepatic transit time is negligible in this experimental scale. The local absorption ratio of metabolite (Fam) was 6.8 ± 1.7% of orally administered 5′-DFUR, which means that ~ 7% of 5′-DFUR arrived as 5-FU at the portal system. The mean local absorption time t¯am of 5-FU was estimated to be 75.5 min, which is close to that (74.0 min) of 5′-DFUR. Local moment analysis based on P–S Difference enabled simultaneous estimation of the local absorption kinetics of a parent compound and the intestinal generation of metabolites by separating the intestinal first-pass metabolism of a drug from the subsequent disposition through the liver and in the systemic circulation.

Doriano Brogioli - One of the best experts on this subject based on the ideXlab platform.

  • boosting the voltage of a salinity gradient power electrochemical cell by means of complex forming solutions
    Applied Physics Letters, 2014
    Co-Authors: M Marino, L Misuri, A Carati, Doriano Brogioli
    Abstract:

    We report experiments on a Concentration cell with zinc electrodes and ZnCl2 solutions at different Concentrations, separated by a porous diaphragm. The cell is aimed at the conversion of the free energy associated to the Concentration Difference into electrical energy, for renewable and clean energy applications. Usually, the diffusion of the solute across the diaphragm constitutes a waste of free energy, which impairs the voltage generation of the Concentration cell with respect to other well-known techniques that work quasi-reversibly, such as reverse electrodialysis or the “mixing entropy battery.” Quite surprisingly, we find that the voltage produced by our Concentration cell is significantly higher than the voltage obtained with the other quasi-reversible techniques. We show that the surplus voltage comes from the active transformation of the mixing free energy into electrical energy performed by the liquid junction, and we show the connection with the negative apparent transference number of the zi...

  • proof of concept of a zinc silver battery for the extraction of energy from a Concentration Difference
    Energies, 2014
    Co-Authors: Massimo Marino, A Carati, L Misuri, Doriano Brogioli
    Abstract:

    The conversion of heat into current can be obtained by a process with two stages. In the first one, the heat is used for distilling a solution and obtaining two flows with different Concentrations. In the second stage, the two flows are sent to an electrochemical cell that produces current by consuming the Concentration Difference. In this paper, we propose such an electrochemical cell, working with water solutions of zinc chloride. The cell contains two electrodes, made respectively of zinc and silver covered by silver chloride. The operation of the cell is analogous to that of the capacitive mixing and of the “mixing entropy battery”: the electrodes are charged while dipped in the concentrated solution and discharged when dipped in the diluted solution. The cyclic operation allows us to extract a surplus of energy, at the expense of the free energy of the Concentration Difference. We evaluate the feasibility of such a cell for practical applications and find that a power up to 2 W per m2 of the surface of the electrodes can be achieved.

  • proof of concept of a zinc silver battery for the extraction of energy from a Concentration Difference
    arXiv: Chemical Physics, 2014
    Co-Authors: Massimo Marino, A Carati, L Misuri, Doriano Brogioli
    Abstract:

    The conversion of heat into current can be obtained by a process with two stages. In the first one, the heat is used for distilling a solution and obtaining two flows with different Concentrations. In the second stage, the two flows are sent to an electrochemical cell that produces current by consuming the Concentration Difference. In this paper, we propose such an electrochemical cell, working with water solutions of zinc chloride. The cell contains two electrodes, made respectively of zinc and silver covered by silver chloride. The operation of the cell is analogous to that of the capacitive mixing and of the "mixing entropy battery": the electrodes are charged while dipped in the concentrated solution and discharged when dipped in the diluted solution. The cyclic operation allows us to extract a surplus of energy, at the expense of the free energy of the Concentration Difference. We evaluate the feasibility of such a cell for practical applications, and find that a power up to 2 W per square meter of surface of the electrodes can be achieved.

Daniele Dini - One of the best experts on this subject based on the ideXlab platform.

  • marangoni effect on small amplitude capillary waves in viscous fluids
    Physical Review E, 2017
    Co-Authors: Li Shen, Fabian Denner, Berend Van Wachem, Neal Morgan, Daniele Dini
    Abstract:

    We derive a general integro-differential equation for the transient behavior of small-amplitude capillary waves on the planar surface of a viscous fluid in the presence of the Marangoni effect. The equation is solved for an insoluble surfactant solution in Concentration below the critical micelle Concentration undergoing convective-diffusive surface transport. The special case of a diffusion-driven surfactant is considered near the the critical damping wavelength. The Marangoni effect is shown to contribute to the overall damping mechanism, and a first-order term correction to the critical wavelength with respect to the surfactant Concentration Difference and the Schmidt number is proposed.