• Toxicological Research
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• 제12권2호
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• pp.223-230
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• 1996

The increased embryotoxicity of the antifolate drug pyrimethamine (PYM) with concomitant dietary dosing of folic acid (FA) was examined in mice. The preventive effects of folinic acid (FNA) on PYM embryotoxicity were also examined. Six groups were constructed: PYM I (pyrimethamine 80 ppm), PYM II (pyrimethamine 150 ppm), PYM II+FNA (pyrimethamine 150 ppm and folinic acid 12 mg/kg/day), PYM II+FA (pyrimethamine 150 ppm and folic acid 350 ppm), FA (folic acid 350 ppm) and a control group. The agents were administered for 7 days from day 6 throughout 12 of gestation. PYM and FA were administered with mashed feed and FNA was intraperitoneally injected. The high incidence of fetal realformations was observed in the PYM II group; these included kinky tail, open eyelids, club foot, cleft palate, absence of the pulmonary lobe, diaphragmatic hernia, fused sternebrae, fused cervical or thoracic vertebral arch, among others. All embryos of the PYM II+FA group were resorbed. No realformed fetuses were observed in the PYM II+FNA group. These results show that the concomitant dosing of FA augments PYM embryotoxicity. The preventive effects of FNA were also observed.

• 대한본초학회지
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• 제25권2호
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• pp.41-54
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• 2010

Objectives : This study was carried out to investigate the anti-toxicity effect of Hwangryunhaedoktang on the dried Mylabris phalerata extract containing cantharidin in ICR mouse. Methods : Dried Mylabris phalerata extracts were orally administered at dosage level 2000, 1000, 500, 250 and 125mg/kg, respectively with and/or without administration of Hwangryunhaedoktang 200mg/kg. During 2 weeks, the changes of body weight, mortality, $LD_{50}$, macroscopic changes of gastrointestinal tract and liver, changes of serum gastrin and somatostatin levels were observed. Results : Decrease of body weight gains was observed in dried Mylabris phalerata extract-dosing groups, but it was significantly developed in Hwangryunhaedoktang extract-dosing groups after dosaging. Increase of mortality rates was observed in dried Mylabris phalerata extract-dosing groups, but it was significantly developed in Hwangryunhaedoktang extract-dosing groups after dosaging. The $LD_{50}$ of dried Mylabris phalerata extract in male mice significantly increased in a case of concomitant used of Hwangryunhaedoktang 268.86 vs 662.05mg/kg. Clinical signs were observed in dried Mylabris phalerata extract-dosing groups, but it was significantly developed in Hwangryunhaedoktang extract-dosing groups after dosaging after dosaging. Increase of number of hemorrhagic and/or erythematous spots in the gastrointestinal tracts, enlargement and congestion in the liver were observed in dried Mylabris phalerata extract-dosing groups, but it was significantly developed in Hwangryunhaedoktang extract-dosing groups after dosaging. Increase of serum gastrin level was observed in dried Mylarbis phalerata extract-dosing groups, these state of abnormal increase was significantly developed in Hwangryunhaedoktang extract-dosing groups after dosaging. Decrease of serum somatostatin level was observed in dried Mylabris phalerata extract-dosing groups, these state of abnormal decrease was significantly developed in Hwangryunhaedoktang extract-dosing groups after dosaging. Conclusions : We could conclude that the Hwangryunhaedoktang has anti-toxicity effect on the dried Mylabris phalerata extract containing cantharidin.

• Clinical and Experimental Pediatrics
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• 제57권3호
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• pp.153-156
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• 2014

Toxic epidermal necrolysis is an unpredictable and severe adverse drug reaction. In toxic epidermal necrolysis, epidermal damage appears to result from keratinocyte apoptosis. This condition is triggered by many factors, principally drugs such as antiepileptic medications, antibiotics (particularly sulfonamide), nonsteroidal anti-inflammatory drugs, allopurinol, and nevirapine. Lamotrigine has been reported potentially cause serious cutaneous reactions, and concomitant use of valproic acid with lamotrigine significantly increases this risk. We describe a case of an 11-year-old girl with tic and major depressive disorders who developed toxic epidermal necrolysis after treatment with lamotrigine, and who was diagnosed both clinically and pathologically. Children are more susceptible to lamotrigine-induced rash than adults, and risk of serious rash can be lessened by strict adherence to dosing guidelines. Unfortunately, in our case, the patient was administered a higher dose than the required regimen. Therefore, clinicians should strictly adhere to the dose regimen when using lamotrigine, especially in children.

• 약학회지
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• 제37권5호
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• pp.463-475
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• 1993

Pharmacological effects of lemakalim on cardiovascular system were investigated using isolated rat hearts and conscious SHRs subjected to hyperkalemic and hypokalemic condition. In the isolated hearts perfused with normal physiological salt solution(4.7 mM KCI), lemakalim increased cardiac function and coronary flow, and these effects were significantly potentiated under hypokalemic(1.2, 2.5 mM KCI), but attenuated under hyperkalemic(IO mM KCI) condition. In conscious SHRS, lemakalim(0.1, 0.2, 0.3mg/kg, p.o.) produced a dose-related decrease in systolic blood pressure, the maximal hypotensive effect being reached around 0.5 hr after dosing. The intensity and the duration of hypotensive effect of lemakalim were significantly increased when administered in combination with dihydrochlorothiazide (2 mg/kg, p.o.), but decreased with triamterene(32 mg/kg, p.o.). It appears that the differential effects of two types of diuretics on the hypotensive action of lemakalim are due to their hypokalemic and hyperkalemic action, respectively. It is conclued that the concomitant use of $K^{+}$ channel openers and hypokalemic diuretics may be an appropriate model of combination therapy in the treatment of hypertension.

• 한국임상약학회지
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• 제28권1호
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• pp.24-29
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• 2018

Background: Cyclosporine is an immunosuppressive agent used to treat and prevent graft versus host reaction (GVHR)-a complication associated with stem cell transplantation. This study aimed to develop a population pharmacokinetic model of cyclosporine and investigate factors affecting cyclosporine clearance in pediatric hematopoietic stem cell transplant patients. Methods: A total of 650 cyclosporine concentrations recorded in 65 patients who underwent hematopoietic stem cell transplantation were used. Data including age, sex, weight, height, body surface area (BSA), type of disease, chemotherapy before stem cell transplantation, type of donor, serum creatinine levels, total bilirubin concentration, hematocrit value, and type of concomitant anti-fungal agents and methylprednisolone used were retrospectively collected. Data related to cyclosporine dosage, administration time, and blood concentration were also collected. All data were analyzed using the non-linear mixed effect model; a two-compartment model with first-order elimination was used. Results: The population pharmacokinetic model of cyclosporine using the NONMEM program was as follows: $CL(L/h)=5.9{\times}(BSA/1.2)^{0.9}$, V2 (L) = 54.5, Q (L/h) = 3.5, V3 (L) = 1080.0, $k_a(h^{-1})=0.000377$. BSA was selected as a covariate of cyclosporine clearance, which increased with an increase in BSA. Conclusion: A population pharmacokinetic model for Korean pediatric hematopoietic stem cell transplant patients was developed, and the important factor affecting cyclosporine clearance was found to be BSA. The model might contribute to the development of the most appropriate dosing regimen for cyclosporine. Further studies on population pharmacokinetics should be carried out, prospectively targeting pediatric patients.

• Toxicological Research
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• 제17권3호
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• pp.225-234
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• 2001

The present study was conducted to investigate the effects of Korean red ginseng water extract (KRGWE) on developmental toxicity caused by the environmental estrogen bisphenol A (BPA) in Sprague-Dawley rats. fifty males successfully mated were randomly assigned to five experimental groups, 1.e., group I (vehicle control), group II (BPA 1000mg/kg), group III (KRGWE 400mg/kg), group IV (BPA 1000mg/kg & KRGWE 200mg/kg), and group V (BPA 1000mg/kg & KRGWE 400mg/kg). The test articles were administered by gavage to mated females from gestational days (GD) 1 through 20 (sperm vaginal lavage=day O). All females were subjected to caesarean section on GD 21 and their fetuses were examined for external, visceral, and skeletal abnormalities. In the group II, significant maternal toxic effects including suppressed body weight, decreased body weight gain during pregnancy, and reduced food consumption were observed in pregnant rats. The minimal developmental toxicity including fetal ossification delay was also found in fetuses. In addition, a tendency for increased pregnancy failure, increased pre-and postimplantation loss, and decreased fetal body weight was observed. However, no fetal morpho-logical abnormalities were seen in surviving fetuses at a dose level of 1000mg BPA/kg. On the other hand, the maternal toxicity and developmental toxicity found in the groups IV and V were comparable to those of the group II. There were no adverse signs of either maternal toxicity or developmental toxicity in the group III. These results showed that administration of BPA at a dose level of 1000mg/kg to pregnant rats resulted in significant maternal toxicity and minimal developmental toxicity, and that no protective effects on BPA-induced maternal toxicity and developmental toxicity were found by concomitant gavage dosing of KRGWE.

• Pediatric Gastroenterology, Hepatology & Nutrition
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• 제22권5호
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• pp.417-430
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• 2019

The policies developed for the treatment of Helicobacter pylori infection in adults may not be the most suitable ones to treat children and adolescents. Methods used to treat children and adolescents in Europe and North America may not be appropriate for treating children and adolescents in Korea due to differences in epidemiological characteristics of H. pylori between regions. Moreover, the agreed standard guidelines for the treatment of H. pylori infection in children and adolescents in Korea have not been established yet. In this study, the optimal treatment strategy for H. pylori infection control in children and adolescents in Korea is discussed based on these guidelines, and recent progress on the use and misuse of antimicrobial agents is elaborated. Non-invasive as well as invasive diagnostic test and treatment strategy for H. pylori infection are not recommendable in children aged less than ten years or children with body weight under 35 kg, except in cases of clinically suspected or endoscopically identified peptic ulcers. The uncertainty, whether enough antimicrobial concentrations to eradicate H. pylori can be maintained when administered according to body weight-based dosing, and the costs and adverse effects outweighing the anticipated benefits of treatment make it difficult to decide to eradicate H. pylori in a positive noninvasive diagnostic test in this age group. However, adolescents over ten years of age or with a bodyweight of more than 35 kg can be managed aggressively as adults, because they can tolerate the adult doses of anti-H. pylori therapy. In adolescents, the prevention of future peptic ulcers and gastric cancers is expected after the eradication of H. pylori. Bismuth-based quadruple therapy (bismuth-proton pump inhibitor-amoxicillin/tetracycline-metronidazole) with maximal tolerable doses and optimal dose intervals of 14 days is recommended, because in Korea, the antibiotic susceptibility test for H. pylori is not performed at the initial diagnostic evaluation. If the first-line treatment fails, concomitant therapy plus bismuth can be attempted for 14 days as an empirical rescue therapy. Finally, the salvage therapy, if needed, must be administered after the H. pylori antibiotic susceptibility test.