5 results on '"Taurocholic Acid pharmacokinetics"'
Search Results
2. The intestinal uptake of phenol from micellar systems does not conform to the aqueous transfer model.
- Author
-
Kothare PA and Zimmerman CL
- Subjects
- Animals, Detergents pharmacokinetics, Intestinal Absorption physiology, Male, Phosphatidylcholines pharmacokinetics, Rats, Rats, Sprague-Dawley, Taurocholic Acid pharmacokinetics, Anti-Infective Agents, Local pharmacokinetics, Jejunum metabolism, Micelles, Phenol pharmacokinetics
- Abstract
Purpose: To evaluate the aqueous transfer model as the mechanism for the micelle-mediated uptake of phenol in the rat in situ intestinal perfusion model., Methods: Phenol in isotonic HEPES buffer was perfused through the jejunal segment at two flow rates and at various concentrations. Phenol was then dispersed in two, distinct mixed micelle systems composed of sodium taurocholate and phosphatidylcholine at 10 mM:2.5 mM (10:2.5 system) and at 10 mM: 10 mM (10:10 system) and its uptake studied in each case. Equilibrium dialysis was done to determine the aqueous fraction of phenol in each system., Results: The P(eff) of phenol in isotonic HEPES buffer at a low flow rate (n = 6) was 1.7 +/- 0.4 x 10(-4) cm/s and at a high flow rate (n = 13) was 1.8 +/- 0.5 x 10(-4) cm/s. The P(eff) for the 10:2.5 system at the high flow rate (n = 3) was 1.5 +/- 0.4 x 10(-4) cm/s and at the low flow rate (n = 3) was 1.4 +/- 0.3 x 10(-4) cm/s. Uptake was membrane rate-limited in both the non-micellar and 10:2.5 systems. P(eff) at a high flow rate (n = 3) in the 10:10 system was 1.3 +/- 0.1 x 10(-4) cm/s. Equilibrium dialysis (n = 4) revealed free fractions of 0.60 +/- 0.05 and 0.50 +/- 0.03 for the 10:2.5 and 10:10 systems., Conclusions: The uptake of micellized phenol did not follow the aqueous transfer model of uptake.
- Published
- 2000
- Full Text
- View/download PDF
3. Intestinal transport of gentamicin with a novel, glycosteroid drug transport agent.
- Author
-
Axelrod HR, Kim JS, Longley CB, Lipka E, Amidon GL, Kakarla R, Hui YW, Weber SJ, Choe S, and Sofia MJ
- Subjects
- Administration, Oral, Animals, Gentamicins administration & dosage, Gentamicins blood, Ileum metabolism, LLC-PK1 Cells, Male, Rats, Rats, Sprague-Dawley, Swine, Taurocholic Acid administration & dosage, Tissue Distribution, Tritium, Drug Delivery Systems methods, Gentamicins pharmacokinetics, Glycosides pharmacokinetics, Intestinal Absorption, Taurocholic Acid analogs & derivatives, Taurocholic Acid pharmacokinetics
- Abstract
Purpose: The objective was to investigate the ability of a glycosteroid (TC002) to increase the oral bioavailability of gentamicin., Methods: Admixtures of gentamicin and TC002 were administered to the rat ileum by injection and to dogs by ileal or jejunal externalized ports, or PO. Bioavailability of gentamicin was determined by HPLC. 3H-TC002 was injected via externalized cannulas into rat ileum or jejunum, or PO and its distribution and elimination was determined. The metabolism of TC002 in rats was evaluated by solid phase extraction and HPLC analysis of plasma, urine and feces following oral or intestinal administration., Results: The bioavailability of gentamicin was substantially increased in the presence of TC002 in both rats and dogs. The level of absorption was dependent on the concentration of TC002 and site of administration. Greatest absorption occurred following ileal orjejunal administration. TC002 was significantly more efficacious than sodium taurocholate, but similar in cytotoxicity. TC002 remained primarily in the GI tract following oral or intestinal administration and cleared rapidly from the body. It was only partly metabolized in the GI tract, but was rapidly and completely converted to its metabolite in plasma and urine., Conclusions: TC002 shows promise as a new drug transport agent for promoting intestinal absorption of polar molecules such as gentamicin.
- Published
- 1998
- Full Text
- View/download PDF
4. Partial maintenance of taurocholate uptake by adult rat hepatocytes cultured in a collagen sandwich configuration.
- Author
-
Liu X, Brouwer KL, Gan LS, Brouwer KR, Stieger B, Meier PJ, Audus KL, and LeCluyse EL
- Subjects
- Animals, Biological Transport, Cells, Cultured, Liver cytology, Male, Rats, Rats, Wistar, Collagen pharmacology, Liver metabolism, Taurocholic Acid pharmacokinetics
- Abstract
Purpose: This study was designed to characterize taurocholate uptake properties in primary cultures of rat hepatocytes maintained under different matrix conditions., Methods: Hepatocytes isolated from male Wistar rats (230-280 g) were cultured on a simple collagen film, on a substratum of gelled collagen or between two layers of gelled collagen (sandwich configuration). Hepatocyte morphology, taurocholate uptake properties, and expression of the sinusoidal transport protein. Na+/taurocholate-cotransporting polypeptide (Ntcp) were examined in these cultures at day 0 and day 5., Results: By day 5, monolayer integrity had deteriorated in simple collagen cultures. In contrast, cell morphology was preserved in hepatocytes maintained in a sandwich configuration. At day 5, taurocholate accumulation at 5 min in hepatocytes cultured on a simple collagen film, on a substratum of gelled collagen, and in a sandwich configuration was approximately 13%, 20% and 35% of day-0 levels, respectively, and occurred predominately by a Na+-dependent mechanism. The initial taurocholate uptake rate vs. concentration (1-200 microM) profile was best described by a combined Michaelis-Menten and first-order function. In all cases, the estimated apparent Km values were comparable for day-0 and day-5 hepatocytes (3241 microM). In contrast, the Vmax values of hepatocytes cultured on a simple collagen film, on gelled collagen and in a sandwich configuration were approximately 5, 6 and 14% of the values at day 0, respectively; values for the first-order rate constant were 5-, 3- and 2-fold lower, respectively. Immunoblot analysis indicated that at day 5 Ntcp expression in hepatocytes cultured in a sandwich configuration was greater than in hepatocytes cultured on a simple collagen film., Conclusions: A collagen sandwich configuration reestablishes normal morphology and partially restores bile acid uptake properties in primary cultures of rat hepatocytes.
- Published
- 1998
- Full Text
- View/download PDF
5. Kinetic analysis of hepatobiliary transport for conjugated metabolites in the perfused liver of mutant rats (EHBR) with hereditary conjugated hyperbilirubinemia.
- Author
-
Takenaka O, Horie T, Kobayashi K, Suzuki H, and Sugiyama Y
- Subjects
- Adenosine Triphosphate metabolism, Animals, Benzothiazoles, Biological Transport, Cholagogues and Choleretics pharmacokinetics, Cytosol metabolism, Glucuronates pharmacokinetics, Hyperbilirubinemia, Hereditary genetics, In Vitro Techniques, Kinetics, Lipoxygenase Inhibitors metabolism, Male, Membranes metabolism, Mutation, Protein Binding, Pyridines metabolism, Rats, Rats, Inbred Strains, Serum Albumin, Bovine metabolism, Sulfates pharmacokinetics, Taurocholic Acid pharmacokinetics, Thiazoles metabolism, Bile metabolism, Bile Canaliculi metabolism, Hyperbilirubinemia, Hereditary metabolism, Lipoxygenase Inhibitors pharmacokinetics, Liver metabolism, Pyridines pharmacokinetics, Thiazoles pharmacokinetics
- Abstract
Purpose: Previously, we found that the biliary excretion of the 6-hydroxy-5,7-dimethyl-2-methylamino-4-(3-pyridylmethyl) benzothiazole (E3040) glucuronide is severely impaired in Eisai hyperbilirubinemic rats (EHBR), while that of sulfate remains normal (Takenaka et al., J. Pharmacol. Exp. Ther., 274: 1362-1369, 1995). The purpose of the present study is to clarify the mechanisms for impairment of the biliary excretion of E3040 glucuronide in EHBR., Methods: We kinetically analyzed the disposition of the conjugates in the perfused liver at steady state. The uptake of the conjugates into the isolated canalicular membrane vesicles (CMVs) was also examined., Results: At steady state, the bile/liver unbound concentration ratios of the conjugates were 40-400 in both rat strains, indicating a highly concentrated process. The biliary excretion clearance (CLu,bile) of the glucuronide, defined for the unbound concentration in the liver, was decreased in EHBR to 1/30 of that in normal rats, whereas the CLu,bile of the sulfate was comparable between the two rat strains. In vitro, the transport of E3040 glucuronide into CMV prepared from SD rats exhibited the ATP dependency, whereas minimal effect of ATP was observed on the uptake of the glucuronide into CMV from EHBR. In contrast, the uptake of E3040 sulfate was comparable between SD rats and EHBR. Furthermore, ATP did not stimulate the uptake of sulfate into the CMVs., Conclusions: It was suggested (1) that the excretion of E3040 glucuronide across the bile canalicular membrane is mediated by the primary active transporter which is defective in EHBR and (2) that the bile canalicular transport system for E3040 sulfate is different from that for the glucuronide in that the former remains normal in EHBR.
- Published
- 1995
- Full Text
- View/download PDF
Catalog
Discovery Service for Jio Institute Digital Library
For full access to our library's resources, please sign in.