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Biomedical subjects

M G Lee

Publications and source records attributed to M G Lee.

At least 163 records · Page 9Linked to original sources
PubMed1998

Stability, blood partition, and pharmacokinetics of a new proton pump inhibitor, YJA-20379-8.

Stability, blood partition, and pharmacokinetics (including tissue distribution and biliary excretion) of YJA-20379-8 were studied using an HPLC analysis. YJA-20379-8 was stable for up to 48 h incubation in a water-bath shaker kept at 37 degrees C and at a rate of 50 oscillations per min in pH solutions ranging from 1 to 14. YJA-20379-8 rapidly reached equilibrium between plasma and blood cells of three rabbit blood, and the equilibrium plasma to blood cell concentration ratios were independent of the initial YJA-20379-8 blood concentrations; the mean values were 1.42-1.56 for three rabbit blood at initial YJA-20379-8 blood concentrations of 1-5 micrograms/ml. As expected from blood partition of the drug between plasma and blood cells, there was no in vitro 'blood storage effect' of YJA-20379-8. After intravenous administration of YJA-20379-8, 10, 20, and 50 mg/kg, to rats, the values of t1/2, MRT, Vss, and CL were dose-independent. However, after intravenous administration of the drug, 5, 10, and 20 mg/kg, to rabbits, the values of t1/2, MRT, and Vss were dose-dependent. After oral administration of the drug, 20, 50, and 100 mg/kg, to rats, the F values (9.00, 16.7, and 11.3% for 20, 50, and 100 mg/kg, respectively) were low considering considerable absorption of the drug from rat gastrointestinal tract (98, 80, and 76% for 20, 50, and 100 mg/kg, respectively) and this could be due to hepatic, gastric, and/or intestinal first-pass metabolism. YJA-20379-8 was under detection limit in urine samples and the contribution of biliary excretion of unchanged YJA-20379-8 to nonrenal clearance of the drug was negligible (less than 0.5% of intravenous dose) in rats, suggesting that the CL (or nonrenal clearance) of YJA-20379-8 could represent metabolic clearance in rats. YJA-20379-8 had a good affinity to almost all rat tissues studied and this was supported by a relatively high value of Vss (3.93-3.93 ml/kg) after intravenous administration of the drug to rats.

Administration, Oral↗
PubMed1998

No effect of probenecid on the renal excretion mechanism of a new carbapenem, DA-1131, in dogs.

The effect of probenecid, an anion transport inhibitor, on the renal excretion mechanism of a new anionic carbapenem, DA-1131, was investigated after 1-min intravenous infusion of DA-1131, 10 mg/kg, with or without probenecid, 50 mg/kg, to dogs. The renal clearance (CL(R)) of DA-1131 in dogs without probenecid (3.18+/-0.247 ml/min/kg) was considerably smaller than the reported creatinine clearance (CL(CR)) in dogs, 6.13 ml/min/kg, indicating that renal tubular reabsorption of the drug was observed in dogs. However, the CLR of DA-1131 was not significantly different (3.18+/-0.247 versus 3.29+/-0.698 ml/min/kg) by treatment with probenecid indicating that the tubular reabsorption of DA-1131 was not inhibited by probenecid.

Absorption↗
PubMed1998

Pharmacokinetics of a new proton pump inhibitor, YJA-20379-8, in rats with 48-hour water deprivation.

The pharmacokinetics of YJA-20379-8 after the intravenous, 20 mg/kg, and oral, 50 mg/kg, administration of the drug, and tissue distribution of YJA-20379-8 after intravenous administration of the drug, 20 mg/kg, to control and 48-h water-deprived rats were reported. After 15-min intravenous infusion of YJA-20379-8, the drug was not detected in urine and less than 0.5% of intravenous dose of the drug was excreted in bile, suggesting that YJA-20379-8 is essentially completely metabolized in rats. Therefore, the CL (clearance) of YJA-20379-8 represents the CLNR (metabolic clearance) of the drug in rats. After oral administration of YJA-20379-8, the F values were low; the values were 21.2 and 19.4% for control and water-deprived rats, respectively. The values were considerably low considering that 93.4 and 84.6% orally administrated YJA-20379-8 were absorbed from rat GI tract of control and water-deprived rats, respectively. This could be due to considerable first-pass (hepatic, gastric, and intestinal) effects. Recently, it was found that gastric and intestinal first-pass effects of YJA-20379-8 were considerable in rats. The amounts of YJA-20379-8 in small intestine, brain, lung, stomach, and kidney increased significantly in water-deprived rats. However, the T/P ratios were comparable (not significantly different) for both groups of rats, indicating that tissue distribution of the drug was not affected by water deprivation.

Administration, Oral↗
PubMed1998

Stability, blood partition, and protein binding of a chemoprotective agent, 2-(allylthio)pyrazine.

The stability of 2-AP, a chemoprotective agent, in various pH solutions and human gastric juice, the blood partition of 2-AP between plasma and blood cells, and the factors influencing the binding of 2-AP to 4% human serum albumin (HSA) were evaluated. 2-AP was stable in human gastric juice and pH solutions ranging from 1 to 12, however, 2-AP was unstable in pH 13 solution; the disappearance rate constant was 0.00759/h. 2-AP reached equilibrium rapidly between plasma and blood cells of rabbit blood. The equilibrium plasma/blood cells partition ratios were independent of initial rabbit blood concentrations of 2-AP, 1, 5, and 10 micrograms/ml; the values were in the range of 5.99-11.8. Binding of 2-AP to 4% HSA was dependent on HSA concentration, incubation temperature, 'the buffer' pH, and addition of acetylsalicylic acid. The binding of 2-AP was independent of buffers containing various concentrations of chloride ion, heparin, and alpha-1-acid glycoprotein.

Animals↗
PubMed1998

Blood sampling site-dependent plasma concentrations and hepatotoxic parameters in serum after intraperitoneal administration of acetaminophen to rats.

Blood sampling site-dependent (the dorsal aorta, the jugular vein, and the retro-orbital sinus) plasma concentrations of acetaminophen and its glucuronide and sulfate conjugates, and acetaminophen-induced hepatotoxic parameters (such as ALT and SDH activity) in serum were evaluated after intraperitoneal administration of acetaminophen, 500 mg/kg body weight, to rats. The plasma concentrations and the resultant AUC0-12 h of acetaminophen, acetaminophen-glucuronide, and acetaminophen-sulfate were significantly higher when blood samples were collected from the retro-orbital sinus than those from the jugular vein. The serum ALT activity at 3 and 24 h after administration of acetaminophen were significantly higher when the blood samples were collected from the retro-orbital sinus than those from the dorsal aorta.

Acetaminophen↗
PubMed1998

Pharmacokinetic changes of a new proton pump inhibitor, YJA-20379-8, after intravenous and oral administration to rats with uranyl nitrate-induced acute renal failure.

Because the physiological changes that occur in patients with acute renal failure could alter the pharmacokinetics of the drugs used to treat the disease, the pharmacokinetics of YJA-20379-8, a new reversible proton pump inhibitor, were investigated after 15-min intravenous (20 mg/kg) and oral (50 mg/kg) administration to control rats and rats with uranyl nitrate-induced acute renal failure (U-ARF). The impaired kidney function was observed in rats with U-ARF on the basis of physiological parameters. After intravenous administration of YJA-20379-8, the pharmacokinetic parameters were not significantly different between two groups of rats except significant increase in volume of distribution at steady state in rats with U-ARF (8000 versus 4520 ml/min). However, after oral administration to rats with U-ARF, AUC(0-16)hr was significantly smaller (126 versus 293 microg min/ml) and this was due to decreased absorption of YJA-20379-8 from gastrointestinal tract; the percentages of oral dose of YJA-20379-8 recovered from gastrointestinal tract at 24 hr as unchanged drug was significantly greater (19.9% versus 6.61%) in rats with U-ARF.

Acute Kidney Injury↗
PubMed1997

Characterization and localization of P2 receptors in rat submandibular gland acinar and duct cells.

[Ca2+]i and the Cl- current were measured in isolated submandibular gland acinar and duct cells to characterize and localize the purinergic receptors expressed in these cells. In both cell types 2'-3'-benzoylbenzoyl (Bz)-ATP and ATP increased [Ca2+]i mainly by activation of Ca2+ influx. UTP had only minimal effect on [Ca2+]i at concentrations between 0.1 and 1 mM. However, a whole cell current recording showed that all nucleotides effectively activated Cl- currents. Inhibition of signal transduction through G proteins by guanyl-5'-beta-thiophosphate revealed that the effect of ATP on Cl- current was mediated in part by activation of a G protein-coupled and in part by a G protein-independent receptor. BzATP activated exclusively the G protein-independent portion, whereas UTP activated only the G protein-dependent portion of the Cl- current. Measurement of [Ca2+]i in the microperfused duct showed that ATP stimulated a [Ca2+]i increase when applied to the luminal or the basolateral sides. BzATP increased [Ca2+]i only when applied to the luminal side, whereas UTP at 100 microM increased -Ca2+-i only when applied to the basolateral side. The combined results suggest that duct and possibly acinar cells express P2z receptors in the luminal and P2u receptors in the basolateral membrane.

Adenosine Triphosphate↗
PubMed1997

Membrane-specific regulation of Cl- channels by purinergic receptors in rat submandibular gland acinar and duct cells.

Measurement of [Cl-]i and the Cl- current in the rat salivary submandibular gland (SMG) acinar and duct cells was used to evaluate the role of Cl- channels in the regulation of [Cl-]i during purinergic stimulation. Under resting conditions [Cl-]i averaged 56 +/- 8 and 26 +/- 7 mM in acinar and duct cells, respectively. In both cells, stimulation with 1 mM ATP resulted in Cl- efflux and subsequent influx. Inhibition of NaKCl2 cotransport had no effect on [Cl-]i changes in duct cells and inhibited only about 50% of Cl- uptake in acinar cells. Accordingly, low levels of expression of NaKCl2 cotransporter protein were found in duct cells. Acinar cells expressed high levels of the cotransporter. Measurement of Cl- current under selective conditions revealed that acinar and duct cells express at least five distinct Cl- channels; a ClCO-like, volume-sensitive, inward rectifying, Ca2+-activated and CFTR-like Cl- currents. ATP acting on both cell types activated at least two channels, the Ca2+-activated Cl- channel and a Ca2+-independent glibenclamide-sensitive Cl--current, possibly cystic fibrosis transmembrane regulator (CFTR). Of the many nucleotides tested only 2'-3'-benzoylbenzoyl (Bz)-ATP and UTP activated Cl- channels in SMG cells. Despite their relative potency in increasing [Ca2+]i, BzATP in both SMG cell types largely activated the Ca2+-independent, glibenclamide-sensitive Cl- current, whereas UTP activated only the Ca2+-dependent Cl- current. We interpret this to suggest that BzATP and UTP largely activate Cl- channels residing in the membrane expressing the receptor for the active nucleotide. The present studies reveal a potentially new mechanism for transcellular Cl- transport in a CFTR-expressing tissue, the SMG. Coordinated action of the P2z (luminal) and P2u (basolateral) receptors can mediate part of the transcellular Cl- transport by acinar and duct cells to determine the final electrolyte composition of salivary fluid.

Adenosine Triphosphate↗
PubMed1997

Determination of a new proton pump inhibitor, YH1885, in human plasma and urine by high-performance liquid chromatography.

A high-performance liquid chromatographic method was developed for the determination of a new proton pump inhibitor, YH1885 (I), in human plasma and urine, and rat blood and tissue homogenate using fenticonazole as an internal standard. The sample preparation was simple: a 2.5 volume of acetonitrile was added to the biological sample to deproteinize it. A 50-microliter aliquot of the supernatant was injected onto a C8 reversed-phase column. The mobile phase employed was methanol-0.005 M tetrabutylammonium dihydrogenphosphate (77:23, v/v), and it was run at a flow-rate of 1.0 ml/min. The column effluent was monitored using an ultraviolet detector at 270 nm. The retention times for I and the internal standard were 9.0 and 10.3 min, respectively. The detection limits for I in human plasma and urine, and in rat tissue homogenate (including blood) were 50, 100 and 100 ng/ml, respectively. The coefficients of variation of the assay (within- day and between-day) were generally low (below 8.84%) for human plasma and urine, and for rat tissue homogenate. No interferences from endogenous substances were found.

Animals↗
PubMed1997

Polarized expression of Ca2+ channels in pancreatic and salivary gland cells. Correlation with initiation and propagation of [Ca2+]i waves.

In polarized epithelial cells [Ca2+]i waves are initiated in discrete regions and propagate through the cytosol. The structural basis for these compartmentalized and coordinated events are not well understood. In the present study we used a combination of [Ca2+]i imaging at high temporal resolution, recording of Ca2+-activated Cl- current, and immunolocalization by confocal microscopy to study the correlation between initiation and propagation of [Ca2+]i waves and localization of Ca2+ release channels in pancreatic acini and submandibular acinar and duct cells. In all cells Ca2+ waves are initiated in the luminal pole and propagate through the cell periphery to the basal pole. All three cell types express the three known inositol 1,4,5-trisphosphate receptors (IP3Rs). Expression of IP3Rs was confined to the area just underneath the luminal and lateral membranes, with no detectable receptors in the basal pole or other regions of the cells. In pancreatic acini and SMG ducts IP3R3 was also found in the nuclear envelope. Expression of ryanodine receptor was detected in submandibular salivary gland cells but not pancreatic acini. Accordingly, cyclic ADP ribose was very effective in mobilizing Ca2+ from internal stores of submandibular salivary gland but not pancreatic acinar cells. Measurement of [Ca2+]i and localization of IP3Rs in the same cells suggests that only a small part of IP3Rs participate in the initiation of the Ca2+ wave, whereas most receptors in the cell periphery probably facilitate the propagation of the Ca2+ wave. The combined results together with our previous studies on this subject lead us to conclude that the internal Ca2+ pool is highly compartmentalized and that compartmentalization is achieved in part by polarized expression of Ca2+ channels.

Adenosine Diphosphate Ribose↗
PubMed1997

Polarized expression of Ca2+ pumps in pancreatic and salivary gland cells. Role in initiation and propagation of [Ca2+]i waves.

The present study was aimed at localization of plasma membrane (PMCA) and intracellular (SERCA) Ca2+ pumps and characterizing their role in initiation and propagation of Ca2+ waves. Specific and polarized expression of Ca2+ pumps was observed in all epithelial cells examined. Immunolocalization revealed expression of PMCA in both the basolateral and luminal membranes of all cell types. SERCA2a appeared to be expressed in the luminal pole, whereas SERCA2b was expressed in the basal pole and the nuclear envelope of pancreatic acini. Interestingly, SERCA2b was found in the luminal pole of submandibular salivary gland acinar and duct cells. These cells expressed SERCA3 in the basal pole. To examine the significance of the polarized expression of SERCA and perhaps PMCA pumps in secretory cells, we compared the effect of inhibition of SERCA pumps with thapsigargine and partial Ca2+ release with ionomycin on Ca2+ release evoked by agonists and Ca2+ uptake induced by antagonists. Despite their polarized expression, Ca2+ uptake by SERCA pumps and Ca2+ efflux by PMCA resulted in uniform reduction in [Ca2+]i. Surprisingly, inhibition of the SERCA pumps, but not Ca2+ release by ionomycin, eliminated the distinct initiation sites and propagated Ca2+ waves, leading to a uniform increase in [Ca2+]i. In addition, inhibition of SERCA pumps reduced the rate of Ca2+ release from internal stores. The implication of these findings to rates of Ca2+ diffusion in the cytosol, compartmentalization of Ca2+ signaling complexes, and mechanism of Ca2+ wave propagation are discussed.

Animals↗
PubMed1997

Determination of a new non-narcotic analgesic, DA-5018, in plasma, urine and bile by high-performance liquid chromatography.

A high-performance liquid chromatographic method was developed for the determination of a new non-narcotic analgesic, DA-5018 (I), in rat plasma, urine and bile samples, using propranolol for plasma samples and protriptyline for urine and bile samples as internal standards. The method involved extraction followed by injection of 100 microliters of the aqueous layer onto a C18 reversed-phase column. The mobile phases were 5 mM methanesulfonic acid with 10 mM NaH2PO4 (pH 2.5)-acetonitrile, 70:30 (v/v) for plasma samples and 75:25 (v/v) for urine and bile samples. The flow-rates were 1.0 ml/min for plasma samples and 1.2 ml/min for urine and bile samples. The column effluent was monitored by a fluorescence detector with an excitation wavelength of 270 nm and an emission wavelength of 330 nm. The retention time for I was 4.8 min in plasma samples and 10.0 min in urine and bile samples. The detection limits for I in rat plasma, urine and bile were 20, 100 and 100 ng/ml, respectively. There was no interference from endogenous substances.

Analgesics, Non-Narcotic↗
PubMed1997

Determination of a new carbapenem derivative, DA-1131, in plasma and urine by high-performance liquid chromatography.

A high-performance liquid chromatographic method was developed for the determination of a new carbapenem, DA-1131 (I), in human plasma and urine and in rat blood and tissue homogenates. The method involved deproteinization of the biological samples with 1 volume each of 0.04 M Ba(OH)2 and ZnSO4 aqueous solution. A 50-microliters aliquot of the supernatant was injected onto a C18 reversed-phase column. The mobile phase employed was 0.015 M KH2PO4-acetonitrile (9:1, v/v) with a pH of 5.0. The flow-rate was 0.8 ml/min. The column effluent was monitored by a ultraviolet detector at 300 nm. The retention time of I was 8.0 min. The detection limits of I in human plasma and urine were 0.1 and 0.5 micrograms/ml, respectively. The coefficients of variation of the assay were generally low (below 8.39%) for human plasma and urine, and rat blood and tissue homogenates. No interferences from endogenous substances were observed.

Animals↗
PubMed1997

The effect of intravenous infusion time on the pharmacokinetics and pharmacodynamics of the same total dose of azosemide in rabbits.

The pharmacokinetics and pharmacodynamics of azosemide were evaluated after intravenous (IV) administration of the same total dose of azosemide, 1 mgkg(-l) in different infusion times, 1 min (treatment I) and 4h (treatment II) to rabbits (n= 5, each). The loss of water and electrolytes in urine induced by azosemide was immediately replaced with infusion of equal volume of lactated Ringer's solution. Some pharmacokinetic parameters of azosemide were different between treatments I and II. For example, the mean value of terminal half-life (70.5 versus 107 min), total body clearance (5.88 versus 8.32 mL min(-1)kg(-1), renal clearance (3.45 versus 6.51mL min(-1)kg(-1), and mean residence time (18.5 versus 31.7min) increased significantly in treatment II. The 8h urine output (236 versus 733mL) and 8h urinary excretion of sodium (29.2 versus 76.4mmol) and chloride (27.5 versus 78.9 mmol) increased significantly in treatment II although the total amount of 8h urinary excretion of unchanged azosemide increased by only 15% in treatment II. This could be due to the fact that the urinary excretion rates of azosemide in treatment II remained for a longer period of time close to the maximally efficient urinary excretion rates of azosemide for both urine output and urinary excretion rates of sodium than in treatment I. Plasma concentrations of azosemide and hourly urine output and hourly urinary excretion of azosemide, sodium, potassium, and chloride during the apparent steady state (between 2 and 4 h) in treatment II were fairly constant.

Animals↗
PubMed1997

Effect of phenobarbital, 3-methylcholanthrene, and chloramphenicol pretreatment on the pharmacokinetics and pharmacodynamics of azosemide in rats.

The effects of pretreatment with the enzyme inducers phenobarbital (PB) and 3-methylcholanthrene (3-MC) and the enzyme inhibitor chloramphenicol (CM) on the pharmacokinetic and pharmacodynamic parameters of azosemide were examined after intravenous (i.v.) administration of azosemide, 10 mg kg-1, to rats. The nonrenal clearance (1.63 versus 3.30 mL min-1 kg-1) of azosemide increased significantly in 3-MC pretreated rats. This suggested that the nonrenal metabolism of azosemide increased by pretreatment with 3-MC. This relationship was supported by the significant decrease in 24 h urinary excretion of unchanged azosemide in 3-MC pretreated rats (54.1 versus 41.1% of i.v. dose). This relationship was also supported at least in part by the results of a liver homogenate study; the amount of azosemide remaining per gram of liver decreased significantly (48.2 versus 43.0 micrograms) and the amount of M1 formed increased significantly (4.88 versus 6.66 micrograms when expressed in terms of azosemide) in 3-MC pretreated rats after 30 min incubation of 50 micrograms azosemide in 9000 g supernatant fractions of liver homogenates. The content of hepatic cytochrome P-450 (0.751 versus 1.57 nmol/mg protein) and the weight of liver (3.53 versus 4.20% of body weight) increased significantly in 3-MC pretreated rats, suggesting that the metabolizing enzyme(s) for azosemide seemed to be induced by pretreatment with 3-MC. The 8 h urine output (29.2 versus 18.1 mL) and 8 h urinary excretion of sodium (4.02 versus 2.39 mmol) and chloride (4.01 versus 2.73 mmol) per 100 g body weight decreased significantly in 3-MC pretreated rats. However, the diuretic, natriuretic, kaluretic, and chloruretic efficiencies were not significantly different between the control and 3-MC pretreated rats. The pharmacokinetic and pharmacodynamic parameters of azosemide were not significantly different between the control and PB pretreated rats, and similar results were also obtained from the control and CM pretreated rats. The above data indicate that the metabolizing enzyme(s) for azosemide seem(s) to be neither induced by PB pretreatment nor inhibited by CM pretreatment. However, the content of hepatic cytochrome P-450 and the weight of liver increased significantly in PB pretreated rats, while the values were not significantly different between the control and CM pretreated rats.

Animals↗
PubMed1997

Effects of the rate and composition of fluid replacement on the pharmacokinetics and pharmacodynamics of intravenous azosemide.

The effects of differences in the rate and composition of intravenous fluid replacement for urine loss on the pharmacokinetics and pharmacodynamics of azosemide were evaluated using rabbit as the animal model. Each rabbit received a 4h constant intravenous infusion of 1 mg kg-1 azosemide with 0% replacement (treatment I, n = 4), 50% replacement (treatment II, n = 5), and 100% replacement (treatment III, n = 5) with lactated Ringer's solution, as well as with 100% replacement with 5% dextrose in water (D-5-W, treatment IV; n = 5). Renal clearance and urinary excretion rate of the drug in treatment III were considerably higher than those in treatments I, II, and IV. In spite of the similarities in kinetic properties, diuretic and/or natriuretic effects of azosemide were markedly different among the four treatments. For example, the mean 8 h urine output values were 98.2, 178, 733, and 237 mL for treatments I-IV, respectively, and the corresponding values for sodium excretion were 11.1, 19.4, 76.4, and 14.2 mmol, and for chloride 13.4, 23.8, 78.9, and 17.1 mmol. Except for treatment III, diuresis and/or natriuresis were found to be time dependent, generally decreasing with time until reaching a low plateau during the later hours of infusion. The present findings also show that (i) no fluid replacement and 100% replacement with D-5-W both produce the same degree (not significantly different) of severe acute tolerance in natriuresis, indicating the insignificance of water compensation in tolerance development; (ii) in treatment II, where neutral sodium balance was achieved, the development of acute tolerance in diuresis can mainly be attributed to negative water balance under this special condition; and (iii) at steady state the hourly diuresis and natriuresis can differ up to about 6.87- and 5.21-fold between treatments. Some implications for the bioequivalence evaluation of dosage forms of azosemide are discussed.

Animals↗
PubMed1997

Pharmacokinetics and pharmacodynamics of furosemide after direct administration into the stomach or duodenum.

The pharmacokinetics and pharmacodynamics of furosemide were compared after an oral administration or a direct administration of Lasix into the duodenum in humans (40 mg). Furosemide was absorbed quickly after a direct administration of Lasix into the duodenum; the peak plasma concentration of furosemide was reached within 1 h in both routes of administration, and the peak concentration was higher in all four subjects after a direct administration into the duodenum than after an oral administration. Furosemide was absorbed considerably after a direct administration of Lasix into the duodenum; the values of the area under the plasma concentration-time curves of furosemide from time zero to 4 h (AUC0-4 h, 93.6 versus 122 micrograms min mL-1, p < 0.123) and the cumulative amounts of the dose excreted in 8 h (10,600 versus 15,000 micrograms, p < 0.0185) and 24 h (11,300 versus 15,400 micrograms, p < 0.0192) urine as unchanged furosemide were significantly higher after a direct administration into the duodenum than after an oral administration. However, the amounts excreted in urine as glucuronide conjugates, a metabolite of furosemide, tended to increase after an oral administration (4030 versus 1670 micrograms as expressed in terms of furosemide, p < 0.0858) when compared to a direct administration into the duodenum, possibly due to the increased gastric first-pass metabolism of furosemide. The 8 h urine output and 8 h urinary excretion of sodium did not increase significantly after a direct administration of Lasix into the duodenum, despite the significantly greater amount of the drug delivered to the active site after a direct administration into the duodenum. This could be explained by the fact that the urinary excretion rates of furosemide after a direct administration into the stomach were closer to the values of maximally efficient urinary excretion rate of furosemide during the 8 h experimental period than after a direct administration into the duodenum.

Administration, Oral↗