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Biomedical subjects

W G Shin

Publications and source records attributed to W G Shin.

16 recordsLinked to original sources

Endoscopic submucosal resection with double ligation technique for treatment of small rectal carcinoid tumors.

BACKGROUND AND STUDY AIMS: It is difficult to achieve complete endoscopic resection of rectal carcinoid tumors without any procedure-related complications. In this study, we evaluated the efficacy and safety of endoscopic submucosal resection with double ligation (ESMR-DL) for the treatment of small rectal carcinoid tumors. PATIENTS AND METHODS: Eleven rectal carcinoid tumors (in 11 patients) were resected by ESMR-DL between November 2001 and April 2004, using a conventional single-channel endoscope with an attached band-ligator device. The lesion was aspirated into the ligator device and an elastic band was placed around the base; a detachable snare was then used to ligate the stalk below the elastic band; and snare resection was performed above the elastic band. The resected specimens were examined with respect to size, histological atypia, depth of invasion, and the histological appearance of the resection margins. RESULTS: All the lesions were excised completely without any complications. There was no tumor invasion beyond the submucosal layer and there was no evidence of atypia in any of the specimens. Tumor diameter varied from 2.0 mm to 10.0 mm (average 6.2 mm). None of the 11 specimens showed histopathological evidence of tumor involvement at the resection margins. There were no immediate or late complications (bleeding or perforation) after ESMR-DL. There was no local recurrence and there were no distant metastases in any patients during the mean follow-up period of 18 months. CONCLUSION: Endoscopic submucosal resection with double ligation is a useful and safe method for the treatment of small rectal carcinoid tumors.

Carcinoid Tumor↗

Effectiveness of raloxifene on bone mineral density and serum lipid levels in post-menopausal women with low BMD after discontinuation of hormone replacement therapy.

OBJECTIVE: To evaluate the effect of raloxifene on bone mineral density (BMD) and serum lipid levels in post-menopausal women who had discontinued hormone replacement therapy (HRT). METHODS: Thirty-four post-menopausal women with low BMD who had taken 60 mg of raloxifene daily for 12 months after discontinuing HRT were evaluated retrospectively. Information about their demographics, fracture history, BMD, lipid profiles and adverse events were collected from medical records and intranet database. The outcome measures were changes in the spine (L2-L4) and femur BMD, serum lipid concentrations, fracture rate and tolerability. RESULTS: The post-menopausal women had a significant increase in their spine (L2-L4) and femur BMD from their baseline BMD [spine, 2.9 +/- 4.6% (P < 0.001); femur, 3.0 +/- 6.6% (P = 0.01)]. Serum low-density lipoprotein (LDL) cholesterol was significantly reduced by 22.6% below baseline after 12 months (P = 0.007). No fractures were observed during therapy. Raloxifene was well tolerated. The most common adverse event was hot flash, which was generally mild. CONCLUSIONS: Raloxifene increases BMD at important skeletal sites, and lowers LDL cholesterol with tolerable adverse events.

Absorptiometry, Photon↗

Bioequivalence of diclofenac injection formulations assessed in Korean males.

A bioequivalence study of diclofenac injection (test formulation (diclofenac potassium): HANA, reference formulation (diclofenac sodium): Shinpoong) was conducted in 18 healthy male Korean volunteers who received each medicine at a dose of 75 mg in a 2 x 2 crossover study. There was a one-week washout period between the doses. Plasma concentrations of diclofenac were monitored by high-performance liquid chromatography over a period of 24 hours after the i.m. injection. AUC0-24 (the area under the plasma concentration-time curve from time 0-24 hours) was calculated by the linear-log trapezoidal method. Cmax (maximum plasma drug concentration) and tmax (time to reach Cmax) were compiled from the plasma concentration-time data. Analysis of variance was carried out using logarithmically transformed AUC0-24 and Cmax, and non-transformed tmax. There were no significant differences between the medications in AUC0-24 and Cmax. The point estimates and 90% confidence intervals for AUC0-24 (parametric) and Cmax (parametric) were 0.973 (0.8971 to 1.0557) and 0.993 (0.9452-1.0451), respectively, satisfying the bioequivalence criteria of the European Committee for Proprietary Medicinal Products and the US Food and Drug Administration Guidelines. The corresponding value for tmax was 0.75 (0.00 to 1.00). Moreover, the modified Pitman-Morgan's adjusted F-test indicated that the bioavailabilities of diclofenac in the two medications were comparable regarding intra- and interindividual variability. Therefore, these results indicate that the two medications of diclofenac are bioequivalent and, thus, may be prescribed interchangeably.

Adult↗

High-performance liquid chromatographic analysis and pharmacokinetics of terazosin in healthy volunteers.

A high-performance liquid chromatographic (HPLC) analysis of terazosin in 1 ml of human plasma was developed using prazosin as an internal standard. The plasma sample was extracted with dichloromethane and ethylether and a 100-microl aliquot was injected onto the reversed-phase column. The mobile phase, 0.02 M sodium phosphate buffer:acetonitrile:tetrahydrofuran = 720:220:60 (v/v/v), was run at a flow rate of 0.8 ml/min and the column effluent was monitored using a florescence detector set at 370 and 250 nm for the emission and excitation wave numbers, respectively. The retention times for terazosin and prazosin were approximately 6.4 and 9.8 min, respectively, and the coefficients of variation of terazosin were generally low, below 6.4%. The present HPLC method was successful for the pharmacokinetic study of terazosin in healthy volunteers. Following oral administration of terazosin, 2 mg, to 20 healthy male volunteers, the area under the plasma concentration-time curve from time zero to time infinity was 421 +/- 71.8 ng h/ml and terminal half-life was 9.83 +/- 1.29 h.

Administration, Oral↗

Pharmacokinetics of theophylline and caffeine after intravenous administration of aminophylline to premature neonates in Korea.

Theophylline has been widely used to treat apnea of premature neonates. The purpose of this study was to compare the pharmacokinetic parameters of theophylline and caffeine after intravenous administration of aminophylline to seven Korean low-birthweight neonates with apnea to those in other countries. The serum concentrations of theophylline and caffeine were measured simultaneously by high-performance liquid-chromatography (HPLC). The mean (+/- S.E.M.) birth weight and gestational period were 1190 +/- 253 g and 31.5 +/- 1.99 weeks, respectively. The mean (+/- S.E.M.) theophylline maintenance dosage was 1.28 +/- 0.15 mg/kg (given as equivalent aminophylline solution) every six hours. The mean (+/- S.E.M.) volume of distribution, 0.937 +/- 0.232 l/kg, elimination rate constant, 0.0249 +/- 0.0095/h, elimination half-life, 32.1 +/- 12.1 h, and total body clearance, 21.7 +/- 6.18 ml/h/kg, of theophylline in Korean premature neonates were comparable to the values of neonates in other countries. For caffeine, the mean (+/- S.E.M.) elimination half-life was 95.1 +/- 25.4 h and the elimination rate constant was 0.0079 +/- 0.0024/h. The mean (+/- S.E.M.) serum concentrations of theophylline and caffeine on the sixth day after aminophylline infusion were 10.4 +/- 2.28 microg/ml (range, 6.38-13.4 microg/ml) and 2.94 +/- 0.98 microg/ml (range, 1.80-4.44 microg/ml), respectively. The mean (+/- S.E.M.) caffeine to theophylline concentration ratio on the day after discontinuation of aminophylline infusion was 0.71 +/- 0.23 (range, 0.39-1.03).

Aminophylline↗

Pharmacokinetic and pharmacodynamic changes of azosemide after intravenous and oral administration of azosemide to uranyl nitrate-induced acute renal failure rats.

The pharmacokinetic and pharmacodynamic differences of azosemide were investigated after intravenous (i.v.) and oral administration of azosemide, 10 mg kg-1, to the control and uranyl nitrate-induced acute renal failure (U-ARF) rats. After IV administration, the plasma concentrations of azosemide were significantly higher in the U-ARF rats and this resulted in a significant increase in AUC (2520 versus 3680 micrograms min mL-1) and significant decrease in Cl (3.96 versus 2.72 mL min-1 kg-1) of azosemide. The significant decrease in Cl in the U-ARF rats was due to the significant decrease in Clr of azosemide (1.55 versus 0.00913 mL min-1 kg-1) due to the decrease in kidney function in the U-ARF rats. After IV administration, the urine output (38.5 versus 8.45 mL 100 g-1 body weight) and urinary excretion of sodium (4.60 versus 0.420 mmol 100 g-1 body weight) decreased significantly in the U-ARF rats. After oral administration, the AUC0-8 h of azosemide decreased significantly (215 versus 135 micrograms min mL-1) in the U-ARF rats possibly due to the decreased GI absorption of azosemide. After oral administration, the 24-h urine output decreased considerably (16.1 versus 11.2 mL 100 g-1 body weight, p < 0.098) and the 24-h urinary excretion of sodium (1.74 versus 0.777 mmol 100 g-1 body weight) decreased significantly in the U-ARF rats. The i.v. and oral doses of azosemide needed to be modified in the acute renal failure patients if the present rat data could be extrapolated to humans.

Acute Kidney Injury↗

Determination of aloesin in plasma by high-performance liquid chromatography.

A high-performance liquid chromatographic method was developed for the determination of aloesin in human plasma. The method involved deproteinization of biological samples with 1 volume of each 0.04 M Ba(OH)2 and 10% ZnSO4 aqueous solution. A 50-microliter aliquot of the supernatant was injected onto a C18 reversed-phase column. The mobile phase, methanol-H2O (20:80, v/v), was run at a flow-rate 1.5 ml/min. The column effluent was monitored by a ultraviolet detector at 254 nm. The retention time of aloesin was 7 min. The detection limit for aloesin in human plasma was 0.1 microgram/ml. The coefficient of variation of the assay was generally low (below 5.04%) for human plasma. No interferences from endogenous substances were observed.

Animals↗

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↗

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↗

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↗

Pharmacokinetics and pharmacodynamics of azosemide after intravenous and oral administration to rats with alloxan-induced diabetes mellitus.

Because physiological changes occurring in diabetes mellitus patients could alter the pharmacokinetics and pharmacodynamics of the drugs used to treat the disease, the pharmacokinetics and pharmacodynamics of azosemide were investigated after intravenous and oral administration of the drug (10 mg kg-1) to control and alloxan-induced diabetes mellitus rats (AIDRs). After intravenous administration of azosemide to the AIDRs, the area under the plasma concentration-time curve (AUC) increased considerably (3120 compared with 2520 micrograms min mL-1; P < 0.135) and the total body clearance decreased considerably (3.20 compared with 3.96 mL min-1 kg-1; P < 0.0593). The considerable reduction in time-averaged total body clearance in the AIDRs was a result of the significant decrease in renal clearance (1.01 compared with 1.55 mL min-1 kg-1) in the AIDRs, the non-renal clearance being comparable between the two groups of rats. After intravenous administration, the 8-h urinary excretion of azosemide (29.5 compared with 40% of intravenous dose; P < 0.0883) and one of its metabolites, M1 (2.15 compared with 2.60% of intravenous dose, expressed in terms of azosemide; P < 0.05) decreased in the AIDRs because of the impaired kidney function. The diuretic, natriuretic, kaliuretic and chloruretic efficiencies increased significantly in the AIDRs. After oral administration of azosemide, AUC decreased significantly in the AIDRs (115 compared with 215 micrograms min mL-1) possibly because of the reduced gastrointestinal absorption of azosemide in the AIDRs. After oral administration of azosemide, the 8-h urine output decreased significantly in the AIDRs (9.32 compared with 16.1 mL per 100 g body weight) because of the significantly reduced 8-h urinary excretion of azosemide (3.00 compared with 9.14% of oral dose). After both intravenous and oral administration some pharmacokinetic and pharmacodynamic parameters of azosemide were significantly different in AIDRs.

Administration, Oral↗

Arterial and venous blood sampling in pharmacokinetic studies: azosemide in rabbits.

The pharmacokinetics of azosemide were evaluated simultaneously using both arterial and venous plasma data in six rabbits after a rapid 5 s intravenous bolus dosing. Initial arterial to venous ratios at 5 s after injection were the highest with values of 81.1, 67.3, 58.7, 530, 2660, and 10.5 for rabbits 1-6, respectively. Both curves decayed, paralleling each other at the terminal phase, with the venous levels higher than the arterial levels by 15.3, 31.9, 34.1, 40.7, 30.5, and 16.5% for rabbits 1-6, respectively. An exponential term with a negative coefficient was used to account for the short and steep rising phase of venous plasma levels after injection. Detailed analysis showed significant differences in various pharmacokinetic parameters, such as initial volume of distribution, apparent volume of distribution at steady state, and mean residence time based on arterial or venous data. A plot of 1/Q (urine flow rate) versus 1/CLR (renal clearance) of azosemide yielded a straight line in six rabbits, indicating that the CLR of azosemide is urine flow dependent in rabbits.

Animals↗

Arterial and venous blood samplings in pharmacokinetic studies: vancomycin in rabbits.

The pharmacokinetics of vancomycin were evaluated simultaneously using both arterial and venous plasma data in five rabbits after a rapid bolus intravenous (i.v.) dosing. Initial arterial to venous concentration ratios at 5 s after i.v. injection were the highest, with values of 27.1, 36.2, 36.6, 43.7 and 29.7 for rabbits 1-5, respectively. This could be the result of diffusion of vancomycin from the arterial plasma into the extravascular tissues. Both curves decayed in parallel at the terminal phase with the venous levels higher than the arterial levels by 23, 37, 34, 13 and 14% for rabbits 1-5, respectively. This difference could be the result of continuous release of vancomycin from the extravascular tissues to the venous blood. Detailed analysis showed differences in various pharmacokinetic parameters based on arterial and venous data. For example, values for venous Vc were 9.2, 11, 1.9, 7.2 and 8.8 times greater than the arterial values for rabbits 1-5, respectively. The values for both venous Vss and MRT were higher than those of the arterial values in all five rabbits studied. This could be due to more extensive distribution of vancomycin in the extravascular tissues. A plot of 1/Q (urine flow rate) versus 1/ClR of vancomycin yielded a straight line in rabbits 6-10, indicating that the renal clearance of vancomycin in rabbits is dependent upon urine flow.

Animals↗

Factors influencing the protein binding of vancomycin.

Various factors influencing the protein binding of vancomycin were examined using equilibrium dialysis method. Four per cent human serum albumin (HSA) and/or 0.08 per cent alpha-1-acid glycoprotein (AAG), dissolved in isotonic phosphate buffer, were dialyzed against isotonic phosphate buffer of pH 7.4 using Spectrapor 2 membrane. The protein binding of vancomycin to 0.08 per cent AAG was dependent on vancomycin concentrations; the values ranged from 21.1 per cent at the vancomycin concentration of 20 micrograms ml-1 to 5.30 per cent at 2400 micrograms ml-1. However, binding to 4 per cent HSA was relatively constant, 8.79 +/- 2.43 per cent over a vancomycin concentration range of 20-2400 micrograms ml-1. The values to 4 per cent HSA alone and 0.08 per cent AAG alone did not predict the greater binding of vancomycin in the presence of both proteins, especially at higher concentrations of vancomycin; the values to 4 per cent HSA with 0.08 per cent AAG were constant, 26.3 +/- 3.74 per cent, at the vancomycin concentration range of 20-2400 micrograms ml-1. This suggested an interaction between the proteins, which resulted in enhanced binding of vancomycin. The protein binding of vancomycin to 4 per cent HSA with 0.08 per cent AAG was not influenced by the different incubation temperatures (4 degrees, 22 degrees, and 37 degrees), quantities of heparin (up to 40 units ml-1) or AAG (up to 0.16 per cent), or buffers (isotonic phosphate buffer of pH 7.4, phosphate buffer of pH 7.4 and 0.9 per cent NaCl solution) at the vancomycin concentration of 80 micrograms ml-1. Vancomycin was found to be stable in human serum albumin or in isotonic phosphate buffer of pH 7.4.

Blood Proteins↗