Blood partition and protein binding of a new reversible proton pump inhibitor, YH1885.
Explore the source record for details and available documents.
Animals↗
Biomedical subjects
M G Lee
Publications and source records attributed to M G Lee.
Pharmacokinetics of a new reversible proton pump inhibitor, YH1885, after intravenous and oral administrations to rats and dogs: hepatic first-pass effect in rats.
The pharmacokinetics of YH1885 were evaluated after intravenous (iv) and oral administrations of the drug to rats and dogs. The reason for the low extent of bioavailability (F) of YH1885 after oral administration of the drug to rats and the absorption of the drug from various rat gastrointestinal (GI) segments were also investigated. After iv administration of YH1885, 5-20 mg kg(-1), to rats, the pharmacokinetic parameters of YH1885 seem to be independent of the drug at the dose ranges studied. After oral administration of YH1885, 50-200 mg kg(-1), to rats, the area under the plasma concentration-time curve from time zero to 12 or 24 h (AUC(0-12 h) or AUC(0-24 h)) was proportional to the oral dose of the drug, 50-100 mg kg(-1), however, the AUC(0-24 h) value at 200 mg kg(-1) increased with less proportion to the dose increase (324, 689, and 815 microg x min mL(-1) for 50, 100, and 200 mg kg(-1), respectively) due to the poor water solubility of the drug. This was proved by the considerable increase in the percentages of the oral dose remaining in the entire GI tract as unchanged YH1885 at 24 h (11.8, 15.3, and 42.8% for 50, 100, and 200 mg kg(-1), respectively). The F value after oral administration of YH1885 to rats was relatively low; the value was approximately 40% at the oral dose of 50 and 100 mg kg(-1). The reason for the low F in rats was investigated. The liver showed the highest metabolic activity for YH1885 based on an in vitro rat tissue homogenate study; hence, the liver first-pass effect was estimated. The value of AUC after intraportal administration of the drug, 5 mg kg(-1), was approximately 70% (116 versus 163 microg x min mL(-1)) of that after iv administration of the drug, 5 mg kg(-1), to rats; the liver first-pass effect of YH1885 in rats was estimated to be approximately 30%. The total body clearance of YH1885 after iv administration of the drug, 5-20 mg kg(-1), to rats were considerably lower than the cardiac output of rats, indicating that the lung and/or heart first-pass effect of YH1885 could be negligible in rats. After oral administration of YH1885, 50 and 100 mg kg(-1), to rats, the F value was approximately 40%, and approximately 15% of the oral dose was recovered from the entire GI tract as unchanged YH1885 at 24 h, and 30% of the oral dose disappeared with the liver first-pass effect. Therefore, the remainder, approximately 15% of the oral dose, could have disappeared with the small intestine first-pass effect and/or degradation of the drug in the GI tract. YH1885 was absorbed from ileum, duodenum, and jejunum of rat, however, YH1885 was under the detection limit in plasma when the drug was instilled into the rat stomach and large intestine. After iv administration of YH1885, 5-20 mg kg(-1), to dogs, the pharmacokinetic parameters of YH1885 also seemed to be independent of the drug at the dose ranges studied. However, after oral administration of YH1885, 0.5 and 2 g per whole body weight, to dogs, the AUC(0-10 h) values were not significantly different (96.8 versus 98.2 microg x min mL(-1)) and this could be due to the poor water-solubility of the drug. YH1885 was not detected in the urine after both iv and oral administration of the drug to both rats and dogs.
Administration, Oral↗
US findings of xanthogranulomatous cholecystitis.
The ultrasound (US) scans of eleven patients with histologically proven xanthogranulomatous cholecystitis have been reviewed. The thickness of the gallbladder (GB) wall, echogenicity of the thickened GB wall, the presence of intramural nodules, gallstones, pericholecystic fluid, loss of wall definition with the liver, and intrahepatic ductal dilatation were specifically assessed by two radiologists. The range of thickness of the GB wall was 3-20mm (mean, 11.2 mm). Thickening was diffuse in nine cases and focal in two. The thickened GB wall, excluding intramural nodules, was echogenic in seven, isoechoic in three and hypoechoic in one, compared with hepatic echogenicity. Intramural nodules were found in eight cases. These were discrete, oval or flat, and of low echogenicity. These ranged in size from 6 to 12 mm (mean, 10.5 mm). Gallstones were present in six cases and there was intrahepatic duct dilatation in two of these. Definition between the liver and the GB was obliterated in seven cases. One case of GB perforation, confirmed at operation, demonstrated pre-operatively a GB wall defect and connection with the surrounding pericholecystic fluid. Pericholecystic fluid was absent in the other 10 cases. Xanthogranulomatous cholecystitis presents ultrasonically as GB wall thickening, and the majority of cases in this series also demonstrated intramural hypoechoic nodules. These findings can be helpful in the diagnosis of xanthogranulomatous cholecystitis.
Adult↗
Acantholytic dyskeratotic epidermal nevus induced by ultraviolet B radiation.
We report a case of acantholytic dyskeratotic epidermal nevus induced by repeated ultraviolet B radiation in a 16-year-old Korean girl. She had experienced pruritic skin rashes on the right side of the abdomen and flank area in a zosteriform distribution for the past 10 years. They were aggravated during the summer and spontaneously disappeared in the winter. Papules revealed acantholytic dyskeratotic cells that were diagnosed as acantholytic dyskeratotic epidermal nevus. Suberythemal and erythemal doses of UVB were irradiated to the lesional skin (right side of abdomen) and nonlesional skin (left side of abdomen) for 4 consecutive days. UVB-induced pruritic papules were observed on the lesional skin and a biopsy specimen of the papules also showed acantholytic dyskeratotic cells, which were compatible with acantholytic dyskeratotic epidermal nevus.
Acantholysis↗
Treatment of multifocal Bowen's disease with a specially designed radioactive skin patch.
Explore the source record for details and available documents.
Adult↗
Circadian changes in the pharmacokinetics and pharmacodynamics of azosemide in rats.
The circadian changes in the pharmacokinetics and pharmacodynamics of azosemide were investigated after intravenous and oral administration of the drug (10 mg kg(-1)) to rats at 1000 or 2200 h. After intravenous administration of azosemide the percentage of the dose excreted in 8-h urine as unchanged azosemide was significantly higher in the 1000 h group than in the 2200 h group (41.7 compared with 28.9%) and this resulted in a significant increase in 8-h urine output (84.7 compared with 36.6 mL/100 g). After intravenous administration the time-averaged renal clearance (CLR) of azosemide was significantly faster (2.86 compared with 1.76 mL min(-1) kg(-1)) and urinary excretion of sodium (46.4 compared with 25.9 mmol/100 g) and chloride (35.6 compared with 18.8 mmol/100 g) increased significantly in the 1000 h group. However, after oral administration, the percentages of oral dose of azosemide excreted in 8-h urine as unchanged azosemide were significantly higher (1.88 compared with 0.67%) and the CL(R) of azosemide was significantly faster (3.64 compared with 0.79 mL min(-1) kg(-1)) in the 2200 h group. This could be at least partly because of increased absorption of azosemide from the gastrointestinal tract in the 2200 h group; the percentages of oral dose of azosemide recovered from the gastrointestinal tract in 8 h as unchanged azosemide was significantly smaller (5.7 compared with 13.2%) in the 2200 h group. The pharmacodynamic parameters of azosemide were not significantly different after oral administration of the drug to both groups of rats. If these data could be extrapolated to man, the intravenous dose of azosemide could be modified on the basis of circadian time.
Administration, Oral↗
Pharmacokinetics of a new carbapenem, DA-1131, after intravenous 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 DA-1131, a new carbapenem antibiotic, were investigated after 1-min intravenous administration of the drug (50 mg/kg of body weight) to control rats and rats with uranyl nitrate-induced acute renal failure (U-ARF rats). The impaired kidney function was observed in U-ARF rats on the basis of physiological parameters observed by microscopy of the kidney and obtained by chemical analysis of the plasma. After a 1-min intravenous infusion of DA-1131, the concentrations in plasma and the total area under the plasma concentration-time curve from time zero to time infinity increased significantly in U-ARF rats compared with those in control rats (13,000 versus 4,400 microg x min/ml). This was due to the significantly slower total body clearance (CL) of DA-1131 (3.84 versus 11.4 ml/min/kg) from U-ARF rats than from control rats. The significantly slower CL of DA-1131 from U-ARF rats was due to both significantly slower renal clearance (0.000635 versus 4.95 ml/min/kg because of a significant decrease in the 8-h urinary excretion of unchanged DA-1131 [1.54 versus 43.8% of the intravenous dose] due to impaired kidney function, as proved by the significant decrease in creatinine clearance [0.0159 versus 4.29 ml/min/kg]) and significantly slower nonrenal clearance (3.80 versus 6.34 ml/min/kg because of a significant decrease in the metabolism of DA-1131 in the kidney) in U-ARF rats. The amounts of DA-1131 recovered from all tissues studied (except the kidneys) were significantly higher for U-ARF rats than for control rats; however, the ratios of the amount in tissue to the concentration in plasma (except those for the kidney, small intestine, and spleen) were not significantly different between the two groups of rats, indicating that the affinity of DA-1131 for rat tissues was not changed considerably in U-ARF rats.
Acute Kidney Injury↗
Biliary stricture caused by blunt abdominal trauma: clinical and radiologic features in five patients.
PURPOSE: To evaluate the clinical and radiologic features of biliary stricture after blunt abdominal trauma and to report the results of endoscopic stent placement. MATERIALS AND METHODS: Medical records and radiologic findings were reviewed in five patients with biliary stricture after blunt abdominal trauma. The level, length, and contour of the strictures were analyzed with endoscopic retrograde cholangiopancreatography (ERCP). Computed tomographic (CT) scans were also reviewed to determine the presence of biliary dilatation, configuration of the injured bile duct, and ancillary abdominal findings. Results from endoscopic stent placement were evaluated in all patients. RESULTS: Stricture occurred in the suprapancreatic portion of the common bile duct in four patients and in the intrapancreatic portion in one patient. At ERCP, the stricture contour was concentric and smooth in three patients, eccentric and smooth in one, and abruptly terminated in one. CT showed abrupt narrowing of the common bile duct with dilatation of the proximal portion in all patients. Endoscopic stent placement was successful in all patients. CONCLUSION: Patients with biliary stricture after blunt abdominal trauma exhibit a delayed onset of symptoms. A correct diagnosis may be difficult on the basis of findings from CT or ERCP alone without a clinical history or evidence of contusions at other sites.
Abdominal Injuries↗
MR cholangiopancreatography of pancreaticobiliary diseases: comparing single-shot RARE and multislice HASTE sequences.
OBJECTIVE: In this study, we compared the single-shot rapid acquisition with relaxation enhancement (RARE) sequence with the multislice half-Fourier acquisition single-shot turbo spin-echo (HASTE) sequence to assess the ability of each technique to show various pancreaticobiliary diseases using MR cholangiopancreatography. SUBJECTS AND METHODS: MR cholangiopancreatography was performed using both the single-shot RARE and the multislice HASTE pulse sequences in 80 consecutive subjects in whom we had proof of a range of diagnoses. The study population included healthy subjects (n = 9), patients with benign lesions (n = 41), and patients with malignant lesions (n = 30). We analyzed each image using the following criteria: the cause of the lesions, the image quality (i.e., the amount of artifact and the sharpness of anatomic structures such as the right and left hepatic ducts, the extrahepatic bile duct, and the main pancreatic duct), and the reviewers' preference of images. The images were evaluated independently by two radiologists who were unaware of the results of the other cholangiopancreatographic sequence and of the diagnosis. RESULTS: Artifacts were less prominent in images that were obtained using the single-shot RARE sequence (p = .0192); however, the sharpness of anatomic structures was the same using either sequence (p = .1673). For images that were obtained using the single-shot RARE technique, the sensitivity, specificity, and accuracy in distinguishing malignant from other abnormalities were 83%, 78%, and 80%, respectively; for the multislice HASTE technique, these values were 77%, 72%, and 74%, respectively (p > .05). Disease-specific accuracy in determining the correct diagnosis was 54% and 59%, respectively (p > .05). In patients in whom all the ducts needed to be defined, the single-shot RARE technique was preferred to the multislice HASTE technique (p < .01). CONCLUSION: The single-shot RARE technique shows fewer artifacts and is preferred to the multislice HASTE technique. However, both techniques show the same degree of sharpness of anatomic structures, both are able to reveal malignant diseases, and both provide enough information to determine a specific diagnosis.
Adult↗
Usefulness of CT in patients with intestinal obstruction who have undergone abdominal surgery for malignancy.
OBJECTIVE: The purpose of this study was to evaluate the usefulness of CT in determining the causes of intestinal obstruction in patients who have undergone abdominal surgery for malignancy. MATERIALS AND METHODS: We analyzed the CT scans of 55 patients with benign (n = 26) or malignant (n = 29) intestinal obstruction that developed after abdominal surgery for malignancy. After calculating the diagnostic accuracy of interpretations by three radiologists, we compared CT findings for benign and malignant intestinal obstructions with respect to peritoneal involvement patterns and other ancillary findings. Multivariate logistic regression analysis was used to determine the diagnostic performance of CT in revealing causes of obstruction. RESULTS: Diagnostic accuracies of the three radiologists were 67%, 75%, and 78%. CT findings indicating malignant obstruction were a mass at the site of obstruction or prior surgery, lymphadenopathy, or an abrupt transition zone and irregular bowel wall thickening at obstructed sites (p < .05). Conversely, the chance for benign obstruction increased when CT revealed mesenteric vascular changes, a large amount of ascites, or a smooth transition zone and smooth bowel wall thickening at the obstructed site (p < .05). With multivariate logistic regression analysis using two variables (a mass at the site of obstruction or prior surgery and lymphadenopathy), we calculated the overall accuracy of CT as 84% (46/55 patients). CONCLUSION: CT is useful in differentiating benign from malignant intestinal obstructions in patients who have undergone abdominal surgery for malignancy. However, CT has limitations in patients not having a demonstrable peritoneal mass.
Abdomen↗
A case of loiasis.
The prevalence of Loa loa infections in non-endemic areas such as Korea is very low, even though it is quite common in the endemic regions of West and Central Africa. We describe a patient who presented with temporary localized edema (classical Calabar swellings) after travelling to Cameroon and in whom the diagnosis of loiasis was made by ELISA. This is the second reported case of loiasis in Korea. As international travel is becoming more frequent, Loa loa infection should be considered in the differential diagnosis for patients with eosinophilia and Calabar swellings in Korea.
Adult↗
Vasculature in hepatocellular carcinoma after transcatheter arterial chemoembolization: comparison of power and color Doppler sonography.
The purpose of this study was to compare power Doppler sonography with conventional color Doppler sonography for the detection of the vascularity of hepatocellular carcinomas after transcatheter arterial chemoembolization. Of the 93 embolized hepatocellular carcinomas, hypervascularity was demonstrated in 36 on angiography; power Doppler sonography correctly identified pulsatile flow signals in 33 (92%) of these 36, whereas color Doppler sonography identified flow signals in 24 (67%). A statistically significant difference was noted when the sizes of the nodules were 30 mm or less. Despite technical difficulties, such as flash artifact, power Doppler sonography is superior to color Doppler sonography for detection of hypervascularity, especially in small embolized nodules of hepatocellular carcinoma (30 mm or less in diameter).
Adult↗
Hepatic and intestinal first-pass effects of a new hepatoprotective agent, YH439, in rats.
First-pass effects of YH439 were evaluated after intravenous, intraportal, oral, and intraduodenal administration of the drug, 100 mg/kg body weight, to rats. The first-pass effects of YH439 in the lung and heart seemed to be negligible based on total body clearance values after intravenous and intraportal administration of the drug to rats compared with cardiac output in rats. Approximately 60% of orally and intraduodenally administered YH439 was not absorbed from rat gastrointestinal tract and the F values of YH439 were less than 0.22% after both administration of the drug to rats. Therefore, it could be concluded that approximately 40% of orally and/or intraduodenally administered YH439 could disappeared by hepatic and/or gastrointestinal first-pass effects. The hepatic first-pass effect of YH439 absorbed into the portal vein was approximately 45% (AUC difference between intravenous and intraportal administration) in rats. The AUC0-8hr values of YH439 after oral (18.7 microg min/ml) and intraduodenal (23.4 microg min/ml) administration were significantly smaller than that after intraportal administration (3260 microg min/ml), however, the values were not significantly different between oral and intraduodenal administration, suggesting that the gastric first-pass effect seemed to be negligible and intestinal first-pass effect was considerable in rats. The low F of YH439 in rats could be mainly due to unabsorption (approximately 60%) and hepatic and intestinal first-pass effect (approximately 40%).
Animals↗
Species differences in pharmacokinetics of a hepatoprotective agent, YH439, and its metabolites, M4, M5, and M7, after intravenous and oral administration to rats, rabbits, and dogs.
Pharmacokinetic parameters of YH439 and its metabolites, M4, M5, and M7, were compared after iv administration of YH439 to rats (1-10 mg/kg), rabbits (1-10 mg/kg), and dogs (1-20 mg/kg) and oral administration of YH439 to rats (50-500 mg/kg) and dogs (0.5-2 g per whole body weight). After oral administration of YH439 to rats, the F values were 3.67, 1.33, and 0.859% for YH439 oral doses of 100, 300, and 500 mg/kg, respectively. However, the F value increased significantly, 21.2%, after oral administration of YH439-contained mixed micelles (10 mg as free YH439) to rats due to increased water solubility of YH439. Species differences in the pharmacokinetics of YH439 and its metabolites were found. First, M7 was detected in both plasma and urine after both iv and oral administration of YH439 to dogs, whereas it was detected neither in rats nor in rabbits, indicating that considerable amount of M7 was formed from YH439 only in dogs. Second, the AUC (or AUC0-->t) ratios of M4 to YH439 after iv administration of YH439 were 24.6-31.3, 42.2-49.2, and 2200-7640% for rats, rabbits, and dogs, respectively, indicating that formation of M4 after iv administration of YH439 was maximal in dogs. Third, the AUC (or AUC0-->t) ratios of M5 to YH439 after iv administration of YH439 were 103-127, 2.93-3.31, and 92.4-158% for rats, rabbits, and dogs, respectively, indicating that formation of M5 after iv administration of YH439 was minimal in rabbits.
Animals↗
Simultaneous determination of a new hepatoprotective agent, YH439, and its metabolites, M4, M5, and M7 in plasma and urine by high-performance liquid chromatography.
A high-performance liquid chromatographic method was developed for the simultaneous determination of YH439, and its metabolites (M4, M5, and M7) in human plasma and rat urine using testosterone as an internal standard. The method involved deproteinization (plasma sample) or extraction (urine sample) followed by injection onto a C18 reversed-phase column. The mobile phase was acetonitrile-0.063 M phosphoric acidisopropyl alcohol (38:48:14, v/v/v), and the flow rate was 1.0 ml/min for the two methods. The column effluent was monitored by a UV detector set at 317 nm. The detection limits for YH439, M4, M5, and M7 in human plasma were 50, 40, 50, and 50 ng/ml, respectively, using the deproteinization method, and the corresponding values in rat urine were 50, 100, 50, and 50 ng/ml using the extraction method. No interferences from endogenous substances were found.
Animals↗
Mechanism of ascorbic acid enhancement of the bioavailability and diuretic effect of furosemide.
The following possible explanations for the significant increases in the oral bioavailability and the diuretic and natriuretic effects of orally administered furosemide observed when ascorbic acid was coadministered to dogs were investigated: ascorbic acid might enhance the gastrointestinal (GI) absorption of furosemide, might inhibit GI wall metabolism of furosemide, might enhance the reabsorption of furosemide from the renal tubules, and might increase the unionized fraction of furosemide at the receptor sites. The significant increase in the oral bioavailability with coadministration of ascorbic acid seemed to result from reduced gastric first-pass metabolism of furosemide and not enhanced GI absorption of furosemide. This might be supported by rat studies; the percentages of the oral doses of furosemide recovered from the GI tract at 8 hr after oral administration were similar (p < 0.583) without (39.5%) and with (44.7%) coadministration of ascorbic acid, and the amounts of furosemide remaining per gram of stomach after 30-min incubations of 50 micrograms of furosemide with 9000g supernatant fractions of stomach homogenates were increased significantly (48.5 vs. 42.4 micrograms) by the addition of 100 micrograms of ascorbic acid. The significant increases in the diuretic and natriuretic effects of furosemide with ascorbic acid could be the result of increases in the reabsorption of furosemide from renal tubules and increases in the unionized fraction of furosemide at the renal tubular receptor sites. This was supported by 1.5-4.2-fold increases in urine output and approximately 20% decreases in the time-averaged renal clearance of furosemide when the urine pH was decreased by 1.5-2.5 units by oral administration of ammonium chloride.
Animals↗
Pharmacokinetics of a chemoprotective agent, 2-(allylthio)pyrazine, after intravenous administration to rabbits.
The pharmacokinetics of 2-(allylthio)pyrazine (2-AP) were evaluated after intravenous administrations of the drug to rabbits. The reason for the multiple peaks in the plasma concentration of 2-AP after intravenous administration of the drug to rabbits were also investigated. After intravenous administration of 2-AP, 10, 20, and 50 mg/kg, to rabbits, the pharmacokinetic parameters of 2-AP, such as the total area under the plasma concentration-time curve from time 0 to 12 h (261, 672, and 1190 micrograms min/ml), the total body clearance (38.3, 42.0, 44.6 ml/min/kg), and the percentages of intravenous dose of 2-AP excreted in 24 h as unchanged drug (0.0306, 0.0252, and 0.0492%), were independent of the dose ranges studied. Since the amount of 2-AP excreted in 12-h bile as unchanged drug after intravenous administration of 2-AP, 20 mg/kg, was only 0.0241 +/- 0.00156%, and some of 2-AP excreted in gastrointestinal tract as unchanged drug was reabsorbed, the reason for the appearance of multiple peaks after intravenous administration of 2-AP could be at least partly due to gastrointestinal excretion of the drug.
Animals↗
Phase I clinical trial: pharmacokinetics of a novel anthracycline, DA-125 and metabolites. Single dose study.
Single dose of DA-125, 20 (n = 3), 40 (n = 3), 60 (n = 3), 80 (n = 6), or 100 (n = 6) mg/m2 body surface area, was administered intravenously in 5 min to 21 patients with various types of cancer as phase I clinical trial. The main side-effects of DA-125 were nausea, vomiting, leukopenia (especially neutropenia), and thrombocytopenia. Among those, hematological side-effects increased with increased doses of DA-125. No patient developed side-effects equal to or higher than grade III up to DA-125 dose of 60 mg/m2. However, at DA-125 dose of 80 mg/m2, 1 out of 3 patients developed grade III leukopenia and grade IV neutropenia. Therefore, 3 additional patients participated taking the dose of 80 mg/m2; no patient developed side-effects equal to or higher than grade III. Hence, DA-125 dose increased to 100 mg/m2. At DA-125 dose of 100 mg/m2, 2 out of 3 patients developed side-effects equal to or higher than grade III and, therefore, 3 additional patients participated taking this dose. Among the 3 additional patients, 1 patient developed both grade III leukopenia and neutropenia. Therefore, further accrual was stopped at this dose (100 mg/m2). The maximally tolerated dose (MTD) of DA-125 was determined to be 100 mg/m2, and the dose-limiting factor for DA-125 was bone marrow suppression. DA-125 dose of 80 mg/m2, 80% of MTD of DA-125, was recommended as the dose for phase II clinical trial. Cardiotoxicity was not observed in any of the 21 patients according to the ECG and RVG. Neither fever, stomatitis, diarrhea, and renal and nervous system toxicity, nor abnormality in blood coagulation was observed in any of the patients, and death or life-threatening side-effects due to DA-125 were also not observed. Antitumor effects of DA-125 were evaluated from the 21 patients; 6 progressive disease, 14 stable disease, and 1 partial response. Pharmacokinetic parameters of M1, such as AUC, t1/2, CL, VSS, and MRT, seemed to be independent of i.v. doses of DA- 125, 20-100 mg/m2 and less than 0.75% of M1 were excreted in 96 h urine when expressed in terms of DA-125 i.v. dose. M2 was the main metabolite of DA-125 among M1-M4 excreted in urine; 10.1 approximately 22.3% of M2 was excreted in 96 h urine when expressed in terms of DA-125 i.v. dose. Bile was collected via the T-tube in 1 additional patient at the dose of 100 mg/m2. Biliary excretion of M1 and M2 was negligible; less than 0.320 and 4.76% of M1 and M2, respectively, were excreted in 96 h bile when expressed in terms of DA-125 i.v. dose.
Adult↗