• Tuberculosis and Respiratory Diseases
• /
• 제40권4호
• /
• pp.357-366
• /
• 1993

연구배경 : $^{99m}Tc$-DTPA의 폐청소율은 폐포상피세포의 손상도를 반영하고 일부 질환에서는 기존의 폐기능검사보다 더 예민한 것으로 알려져 있다. 흡입된 $^{99m}Tc$-DTPA의 폐청소율은 $^{99m}Tc$-DTPA가 침착되는 부위에 의해 많은 영향을 받아 체외에서 감마카메라로 폐의 방사능 소실속도를 측정하는 방법으로는 섬모운동에 의한 청소속도와 폐포상피를 통한 흡수속도를 구분 할 수 없어 전체 폐의 방사능 소실속도가 폐포상피세포의 투과성만을 반영한다고 할 수 없고 또 장시간동안 감마카메라로 촬영을 해야하는 등 방법이 복잡하다. 흡입된 $^{99m}Tc$-DTPA는 체내에서 24시간 이내에 모두 소변으로 배설되고, 첫 2시간동안 소변으로 배설되는 $^{99m}Tc$-DTPA량은 폐포상피세포를 통한 흡수속도에 의해 결정된다고 알려져 있어, 본 연구자들은 2시간과 24시간 소변내의 방사능배설량의 비를 이용하여 간편하게 폐청소율을 구하는 방법의 유용성 여부를 관찰하기 위해 본 연구를 시행하였다. 방법 : 비흡연 정상인과 미만성 간질성 폐질환환자들을 대상으로 폐기능 검사를 시행하였고 $^{99m}Tc$-DTPA를 vaporizer를 통하여 5분간 흡입후 앙와위에서 폐의 후부상을 감마카메라로 1분단위영상방식으로 30분간 컴퓨터에 수록하여 폐방사능 반감기($T_{1/2}$)를 구하였으며, 또 흡입후 2시간과 24시간 소변을 모아 2시간대 24시간 소변내 방사능배설량비를 구하여 다음과 같은 결과를 얻었다. 결과: 1) 비흡연 정상인에서 $T_{1/2}$와 2시간대 24시간 소변내 방사능배설량비간에는 통계적으로 의미있는 역상관관계가 관찰되었다(r=-0.77, p<0.05). 미만성 폐질환 환자에서 폐방사능 반감기와 2시간대 24시간 소변내 방사능배설량비간에도 역시 의미있는 역상관관계가 관찰되었다 (r=-0.63, p<0.05). 2) 미만성 간질성 폐질환 환자에서 $T_{1/2}$는 $38.65{\pm}11.63$분으로 비흡연 정상인의 $55.53{\pm}11.15$분에 비하여 통계적으로 유의하게 짧았으며, 2시간대 24시간 소변내 방사능배설량비 역시 미만성 간질성 폐질환 환자에서 $52.15{\pm}10.07%$로 비흡연 정상인의 $40.43{\pm}5.53%$에 비해 유의하게 증가되어 있었다(p<0.05). 3) $T_{1/2}$나 2시간대 24시간 소변내 방사능배설량비는 환자군에서 폐확산능과 유의한 상관관계가 없었다(p>0.05). 결론 : 이상의 결과로 $^{99m}Tc$-DTPA의 2시간대 24시간 소변내 방사능배설량비는 폐포상피세포의 투과성을 잘 반영하여 폐포상피세포의 손상정도를 반영하는 간편한 bedside 검사로 생각되며 특히, 폐포상피세포 투과성이 증가되어 있는 미만성 간질성 폐질환 환자에서 예민한 추적경사로 폐확산능과 상호보완적으호 유용하게 사용될 수 있을 것으로 생각된다.

• Biomolecules & Therapeutics
• /
• 제21권2호
• /
• pp.170-172
• /
• 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
• /
• 제8권3호
• /
• pp.275-280
• /
• 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.

• 대한약리학회지
• /
• 제10권2호
• /
• pp.63-74
• /
• 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.

• 한국환경보건학회지
• /
• 제36권6호
• /
• pp.510-517
• /
• 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
• /
• 제14권3호
• /
• pp.105-121
• /
• 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.

• 분석과학
• /
• 제13권3호
• /
• pp.385-393
• /
• 2000

뇨시료 중 amineptine의 (dihydro-10, 11-dibenzo[a, d] cycloheptenyl-5-amino-7-heptanoic acid) metabolites를 분석하기 위한 최적조건을 찾기 위하여 pH 변화에 따른 추출률과 세가지의 유도체화시약에 대한 반응성을 조사해본 결과 pH는 9.5, 유도체화시약은 carboxylic acid group에 MSTFA로 반응 시켰을 경우 좋은 결과를 나타내었다. GC/MS를 이용하여 amineptine을 복용한 사람의 뇨를 분석한 결과 amineptine과 그 대사물질인 dihydro-10, 11-dibenzo[a, d] cycloheptenyl-5-amino-5-pentanoic acid ($C_5$-metabolite)와 $C_5$-metabolite의 lactamized product인 ${\delta}$-lactam을 확인하였다. Amineptine과 그 metabolite들을 GC/MS-SIM mode로 분석하기 위한 monitoring ion들은 m/z 192를 공통 이온으로 선정하였으며, 각각의 분자이온을 선정하였다. Amineptine의 excretion study 결과, amineptine, ${\delta}$-lactam 및 $C_5$-metabolite는 4시간이내에 70-90%가 배설되었고 20시간 이내에 거의 배설이 완결되었다.

• 대한약리학회지
• /
• 제19권2호
• /
• pp.17-24
• /
• 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
• /
• 제34권3호
• /
• pp.161-168
• /
• 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
• /
• 제8권1호
• /
• pp.19-23
• /
• 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.