• Tuberculosis and Respiratory Diseases
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• v.40 no.4
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• pp.357-366
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• 1993

Background: Lung clearance of inhaled $^{99m}Tc$-DTPA reflects alveolar epithelial permeability and it had been reported as more sensitive than conventional pulmonary function tests in detecting lung epithelial damage. However, measuring lung clearance of inhaled $^{99m}Tc$-DTPA by gamma camera may not always reflect alveolar epithelial permeability exactly because it is influenced by mucociliary clearance depending on the site of particle deposition. Moreover, this method takes much time and patient's effort because he has to sit or lie still in front of the camera for a prolonged period. Most of the absorbed DTPA is excreted in urine within 24 hours and the amount of excreted DTPA in urine during the first few hours after inhalation is influenced by absorption rate which is correlated with the alveolar-epithelial permeability suggesting that the urinary excretion, especially in first few hours, may be an alternate index for lung clearance. The purpose of this study was to evaluate the usefulness of ratio of excreted $^{99m}Tc$-DTPA in 2 hour and 24 hour urine as an index of alveolar-epithelial damage. Methods: Pulmonary function tests including diffusing capacity and lung clearance of $^{99m}Tc$-DTPA measured by gama camera ($T_{1/2}$) and 2hr/24hr urine excretion ratio (Ratio) of inhaled $^{99m}Tc$-DTPA in 8 normal subjects and 14 patients with diffuse interstitial lung disease were compared. Results: 1) In the normal control, there was significant negative correlation between the $T_{1/2}$ and the Ratio (r=-0.77, p<0.05). In patients with diffuse interstitial lung disease, there also was significant negative correlation between $T_{1/2}$ and Ratio(r=-0.63, p<0.05). 2) In diffuse interstitial lung disease patients, the $T_{1/2}$ was $38.65{\pm}11.63$ min which was significantly lower than that of normal control, $55.53{\pm}11.15$ min and the Ratio was $52.15{\pm}10.07%$ also signifantly higher than that of the normal control, $40.43{\pm}5.53%$ (p<0.05). 3) There was no significant correlations between $T_{1/2}$ or Ratio and diffusing capactiy of lung in both patients and controls (p>0.05). Conclusion: These results suggests that 2hr/24hr urine excretion ratio of inhaled $^{99m}Tc$-DTPA is a useful simple bedside test in assessing alveolar epithelial permeability and that it may be used as an additive follow-up test in patients with diffuse interstitial lung disease complementing conventional pulmonary function tests.

• Biomolecules & Therapeutics
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• v.21 no.2
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• pp.170-172
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• 2013

The pyrimidine nucleoside uridine has recently been reported to have a protective effect on cultured human corneal epithelial cells, in an animal model of dry eye and in patients. In this study, we investigate the pharmacokinetic profile of uridine in rabbits, following topical ocular (8 mg/eye), oral (450 mg/kg) and intravenous (100 mg/kg) administration. Blood and urine samples were serially taken, and uridine was measured by high-performance liquid chromatography-tandem mass spectrometry. No symptoms were noted in the animals after uridine treatment. Uridine was not detected in either plasma or urine after topical ocular administration, indicating no systemic exposure to uridine with this treatment route. Following a single intravenous dose, the plasma concentration of uridine showed a bi-exponential decay, with a rapid decline over 10 min, followed by a slow decay with a terminal half-life of $0.36{\pm}0.05$ h. Clearance and volume of distribution were $1.8{\pm}0.6$ L/h/kg and $0.58{\pm}0.32$ L/kg, respectively. The area under the plasma concentration-time curves (AUC) was $59.7{\pm}18.2{\mu}g{\cdot}hr/ml$, and urinary excretion up to 12 hr was ~7.7% of the dose. Plasma uridine reached a peak of $25.8{\pm}4.1{\mu}g/ml$ at $2.3{\pm}0.8$ hr after oral administration. The AUC was $79.0{\pm}13.9{\mu}g{\cdot}hr/ml$, representing ~29.4% of absolute bioavailability. About 1% of the oral dose was excreted in the urine. These results should prove useful in the design of future clinical and nonclinical studies conducted with uridine.

• Asian-Australasian Journal of Animal Sciences
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• v.8 no.3
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• pp.275-280
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• 1995

The effect of supplemented high protein diet intake on renal urea regulation in swamp buffalo was carried out in the present experiment Five swamp buffalo heifers weighing between 208-284 kg were used for this study. The animals were fed with a supplementary high protein diet and renal function and kinetic parameters for urea excretion were measured. This was compared to a control period where the same animals had been fed only with paragrass and water hyacinth. For 2 months the same animals were fed a mixed of paragrass, water hyacinth plus 2 kgs of a high protein supplement (protein 18.2% DM basis) per head per day. In comparison to the control period, there were no differences in the rate of urine flow, glomerular filtration rate (GFR), effective renal plasma flow (ERPF), plasma urea concentration and filtered urea. In animals supplemented with high protein intake mean values of urea clearance, excretion rate and the urea urine/plasma concentration ratio markedly increased (p < 0.05) while renal urea reabsorption significantly decreased from 40% to 26% of the quantity filtered. In this same study group urea space distribution and urea pool size increased which coincided with an increase in plasma volume (p < 0.05). Plasma protein decreased while plasma osmolarity increased (p < 0.05). Both urea turnover rate and biological half-life of $^{14}C$-urea were not affected by a supplementary high protein intake. The results suggest that animals supplemented with high protein diets are in a state of dynamic equilibrium of urea which is well balanced between urea excreted into the urine and the amount synthesized. The limitation for renal tubular urea reabsorption would be a change in extra-renal factors with an elevation of the total pool size of nitrogenous substance.

• The Korean Journal of Pharmacology
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• v.10 no.2
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• pp.63-74
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• 1974

This study was carried out to observe the direct effect of hydrocortisone on renal function by infusing it into a renal artery. Hydrocortisone (5mg/kg) or saline (0.5 ml/kg) was infused directly into the left renal artery of the rabbit, the right kidney was left intact to serve as a control for general action of acetazolamide (10 mg/kg) or aminophylline (10 mg/kg), which was administered intravenously 30 minutes after the direct infusion of pretreated drugs (hydrocortisone or saline). The changes of urine volume, pH, urinary excretion rates of $Na^+,\;K^+\;and\;Cl^-$, and the clearances of inulin and PAH were measured at an interval of 10 minutes for half an hour after the direct infusion of hydrocortisone or saline, and for one hour after intravenous administration of acetazolamide or aminophylline. The results of the experiment were as follows: 1. Significant changes in urine volume and urinary electrolytes (excreted rates of $Na^+,\;K^+\;and\;Cl^-$) were observed in the hydrocortisone-infused group 10 minutes after the administration of acetazolamide, compared with the saline-infused group. Especially, the effect was more potent on the infused (left) side than on the contralateral (right) side. 2. Significant changes in urine volume and urinary electrolytes were also observed in all the aminophylline-treated groups, but no remarkable difference was noticed between the hydrocortisone-infused group and the saline-infused group, nor between the left and right sides. 3. No signicant changes in the clearances of inulin and PAH were in the infused (left) side of all the experimental groups, as compared with the contralateral (right) side. From the above results, it is obvious that hydrocortisone infused into a renal artery exerts diuretic action when administered in combination with acetazolamide, and the mechanism of action rests not on its hemodynamic change for renal blood flow, but on the potentiation of carbonic anhydrase inhibiting action. However, the exact mode of action remains yet to be clarified.

• Journal of Environmental Health Sciences
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• v.36 no.6
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• pp.510-517
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• 2010

Phthalates, such as di (2-ethylhexyl) phthalate (DEHP), dibutyl phthalate (DBP) have been proved to be teratogenics and endocrine disruptors, metabolized rapidly and excreted in the urine. In this study, a simultaneous analytical method for 10 phthalate metabolites, MnBP, MiBP, MBzP, MCHP, MEHP, MEHHP, MEOHP, MnOP, MiNP and MiDP, in human urines, based on switching system with on-line pretreatment column using HPLC-MS/MS has been developed. This method was validated according to the guideline of bioanalytical method validation of National Institute of Toxicological Research. Limits of detection range between 0.2 and 0.9 ng/ml for 10 phthalate metabolites. The calibration curves showed linearity in the range 0.997~0.999, and the results of the intra- and inter-day validations were in the range from 0.4 to 14.7% RSD and from 0.3 to 9.4% RSD, respectively. Recoveries of phthalate metabolites varied from 87.0 to 116.1%. This analytical method showed high accuracy and stable precision for all metabolites, and seems to be suitable for biomonitoring of phthalates in human urine.

• Journal of Pharmaceutical Investigation
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• v.14 no.3
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• pp.105-121
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• 1984

The bioavailability of rifampicin (brand A, B and C) was studied and the dissolution by foamed plastic rotating method and basket rotating method was also investigated. The results were as follows; 1. In the case of foamed plastic rotating method, it was revealed that dissolution rate of brand C was most rapid, but in the case of basket rotating method the results revealed that brand B was most rapid. Also it was observed that the dissolution rate in artificial gastric juice was more rapid than one in artificial intestinal juice, and that Avicel added in capsule increased additively the dissolution rate, particulary brand B. 2. Relative systemic availability by urine data showed that the results from all capsules filled with brand A, B and C were identical but in the case of the ripamficin capsules filled with Avicel, the results showed that Avicel increased the availability of brand A and B. 3. Area under serum concentration curve $(0{\sim}8hrs)$ was in order of $brand\;A{\fallingdotseq}brand\;C$ > brand B, but Avicel increased significantly the AUC of brand B and showed no effect in others. 4. Relative systemic availability calculated with excreted amount of rifampicin in urine was similar in each rifampicin capsules. In rifampicin (A) and rifampicin (B), Avicel which added in capsules appeared increasing tendency in urine excretion of rifampicin, but in rifampicin (C) it did not appeared. 5. Area under serum concentration curve $(0{\sim}8hrs)$ in rifampicin capsules was in order of $rifampicin(A){\fallingdotseq}rifampicin(C)$>rifampicin(B). In rifampicin (B) with Avicel capsules, area under serum concentration curve (0-8hrs.) increased significantly and in others insignificantly.

• Analytical Science and Technology
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• v.13 no.3
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• pp.385-393
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• 2000

A gas chromatography-mass spectrometric (GC/MS) procedure for the determination of amineptine (dihydro-10, 11-dibenzo[a, d] cycloheptenyl-5-amino-7-heptanoic acid) and its main metabolites in human urine was described. Amineptine has been known to be extensively metabolized by the ${\beta}$-oxidation of the heptanoic side chain with formation of pentanoic side chain metabolite ($C_5$-metabolite), and lactamizarion by internal dehydration of (${\beta}$-oxidized metabolite (${\delta}$-lactam). The detection of these compounds was based on acid hydrolysis, liquid-liquid extraction and trimethylsilylated derivatization of the carboxylic acid group. For the determination of amineptine and its metabolites in biological fluids, selected ions at the m/ 192, molecular ion and one of the characteristic ions were monitored by GC/MS. On the excretion study of amineptine in human urine, 70-90% of amineptine, ${\delta}$-lactam, and $C_5$-metabolite were found to be excreted within 4 hours and their excretion completed within 20 hours.

• The Korean Journal of Pharmacology
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• v.19 no.2
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• pp.17-24
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• 1983

Buxus leaves(Buxus microphylla var. koreana Nakai) have been used as a folk medicine in treating woman's disease. The chemical constituents, which have teen identified from Buxus sempervirens L. in Europe, are so far known in isolation of buxus alkaloids, cyclobuxine, buxamine, norbuxamine and buxaminol. But But any study on the pharmacological action of Buxus microphylla var. koreana Nakai has not yet teen rallied out, however, active substances have not been identified. As an attempt to isolate the biologically active substances from this plant, the examination of chemical constituents was undertaken. In the experiment, the crystalline component$(C_{10}H_8O_4)$ obtained from Buxus microphylla var. koreana Nakai was identified as a 6-methoxy, 7-hydroxy coumarin by chemical and physical methods. We named this crystal buxuletin. Therefore, we intended to screen the pharmacological action of buxuletin, especially, its diuretic effects in rabbits. Buxuletin was intraveneously injected to the rabbit in the dose of 20 mg/kg, 10 mg/kg and 5 mg/kg. The variations of urine volume and minerals $(Na^+,\;K^+\;and\;Cl^-)$ in urine were measured at an interval of 15 minutes for 4 hours after the treatment of buxuletin. The observed results are as follows: 1) With the administration of buxuletin (20 mg/kg, 10 mg/kg), the remarkable increment of the excreted urine volume was observed during the relatively long period. Excretion rates of urinary minerals $(Na^+,\;K^+\;and\;Cl^-)$ were also increased. 2) In a dose of 5 mg/kg, the slight increment on the diuretic actions of rabbits was observed. From the above results, authors name this crystal buxuletin and buxuletin shows the diuretic action.

• Journal of Pharmaceutical Investigation
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• v.34 no.3
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• pp.161-168
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• 2004

5-Fluorouracil (5-FU) is an antimetabolite anticancer agent active against many types of solid tumors. Tegafur (TF), a prodrug of 5-FU, is frequently used in combination with uracil as dihydropyrimidine dehydrogenase (DPD) inhibitory fluoropyrimidine. We studied the stability of 5-FU and TF in biological fluids of rats and determined their bioavailability (BA) and excretion into bile, and urine. The drug concentrations were analyzed by an HPLC method. At room temperature, there was a 14-30% decrease in the concentration of 5-FU and TF in bile, urine, and plasma specimen at 10 and $100\;{\mu}g/ml$ over 240 min. No significant difference was noted among the sample types or between two different concentrations of 10 and $100{\mu}g/ml$. The decrease in drug concentration was significantly less in samples kept on ice (6-12%) for both drugs. These data indicate that biological fluid samples containing 5-FU or TF in plasma, urine, or bile should be placed on ice during the sample collection. Following these storage guidelines, samples were collected after administration 50 mg/kg of each drug via i.v. or oral route. BA was 1.5 folds greater for TF (60%) than that of 5-FU (42%). Approximately 0.52 and 3.3% of the i.v. doses of 5-FU and TF was excreted into bile, respectively. Renal clearance of 5-FU was about 16% of its total body clearance. These results suggest that instability of 5-FU and TF in biological fluids should be considered in pharmacokinetic or pharmacogenomic studies.

• Preventive Nutrition and Food Science
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• v.8 no.1
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• pp.19-23
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• 2003

Dimethylamine (DMA) is the immediate precursor of carcinogenic N-nitrosodimethylamine (NDMA). In vitro and in vivo experiments using whole strawberries, and garlic and kale juices were conducted to determine concentrations of DMA and trimethylamine (TMA) in foods and urine. Experimental diets [an amino-rich diet as nitrosatable precursors in combination with added nitrate-containing drinking water without (TD1) or with whole strawberries or garlic or kale juices (TD2, TD3 and TD4, respectively), or a diet of low in nitrate and amino (TD5) were incubated in simulated saliva and gastric juices at 37$^{\circ}C$ for 1 hour. We also studied the urinary excretion of DMA and TMA after consumption of the experimental diets (TD1~TD5). Urine samples were obtained for 18 hrs after consumption of experimental diets and concentrations of DMA and TMA were measured in the digested diet and urine. The DMA concentration after incubation in experimental diets (TD1~TD5) was 4.7$\pm$0.3, 6.7 $\pm$0.2, 7.9$\pm$0.2, 7.1$\pm$0.2 and 0.3$\pm$0.1 mg/kg, respectively. Urinary excretion of DMA (TD1~TD5) was 22.0$\pm$5.0, 28.3$\pm$4.3, 29.2$\pm$4.1, 27.4$\pm$4.5 and 20.4$\pm$3.1 mg/18 hr, respectively. Consumption diets with added strawberries or juices of kale or garlic increased urinary TMA and DMA, suggesting that those precursors were excreted and not converted to the carcinogen, NMDA.