• 약학회지
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• 제57권6호
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• pp.412-419
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• 2013

Drug discovery and development processes are time consuming and costly endeavors. It has been reported that on average it takes 10 to 15 years and costs more than $ 1billion to bring a molecule from discovery to market. Compounds fail for various reasons but one of the significant reasons that accounts for failures in clinical trials is poor prediction/understanding of pharmacokinetics and drug metabolism in human. In an effort to improve the number of compounds that exhibit optimal absorption, distribution, metabolism, elimination (ADME), and pharmacokinetic properties in human, drug metabolism, pharmacokinetic scientists have been continually developing new technologies and compound screening strategies. Over the last few years, accelerator mass spectrometry (AMS) and its applications to preclinical/clinical pharmacokinetics and ADME studies have significantly increased, particularly for new chemical/biological entities that are difficult to support with conventional radiolabel studies. In this review, the application of AMS for micro-dosing, micro-tracer absolute bioavailability, mass balance and metabolite profiling studies will be discussed.

• Journal of Pharmaceutical Investigation
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• 제30권2호
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• pp.113-118
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• 2000

In order to assay the efficacy of newly synthesized antiviral compounds, pyrimidine analogs, pharmacokinetics of those were established as compared with already marketed zidovudine. Zidovudine (15, 20, 25 and 35 mg/kg), LJ142 (18.52 mg/kg) and LJ143 (15, 18.52 and 30 mg/kg) were administered orally and intravenously in rats, blood samples were collected post-injection(i.e., for 360 min) at appropriate time intervals. Those were analyzed by HPLC with UV detection at 265 nm. Pharmacokinetic parameters $(C_{max},\;T_{1/2},\;MRT,\;AUC,\;AUMC,\;Vd_{SS},\;Cl_t)$ were calculated. AUCs of zidovudine and LJ143 following I.V. dosing of $15{\sim}25\;mg/kg\;and\;15{\sim}18.18\;mg/kg$ were dose-independent. However, AUCs of zidovudine and LJ43 following I.V. dosing of $25{\sim}35\;mg/kg\;and\;18.18{\sim}30\;mg/kg$ were dose-dependent. The relative bioavailability of zidovudine, LJ142 and LJ143 following oral administration were 61.94, 46.44 and 78.24%, respectively.

• 한국동물위생학회지
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• 제25권3호
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• pp.299-308
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• 2002

The purposes of this study were to characterize the disposition of sulfathiazole(ST) and to investigate the effects of sodium bicarbonate on the disposition of ST in broiler chicks(2.5～3.0kg). Animals were given ST acutely(10～80mg/kg, PO), and plasma, kidney, muscle, heart, liver and spleen samples were collected and analyzed for ST by high performance liquid chromatography. The plasma and tissue data was consistent with a one-compartment pharmacokinetic model. The drug is rapidly but incompletely(2.5～3.87%) absorbed with peak plasma and tissue levels being achieved within one hour after dosing. The plasma and tissue levels depended on drug dosage, and the descending order in concentration of ST was kidney > plasma > heart > muscle $\geq$ spleen $\geq$ liver from animals sacrificed at one hour after dosing. Moreover, significant positive correlations(r>0.9) existed between plasma and tissue levels of ST. In addition, sodium bicarbonate pretreatment decreased plasma level, indicating that an alkalinization stimulate the excretion of ST. Results of this study suggest that oral application of ST was rapidly absorbed and eliminated, and confirmed that tissue residues of ST can be estimated from plasma drug concentration in broiler chicks.

• 동의생리병리학회지
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• 제17권4호
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• pp.980-990
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• 2003

The effect of Gamigyuibi-tang on the penile erection induced by apomorphine HCI and on the erectile dysfunction induced by p,p-DDE, an environmental hormone derivate of DOT, were monitored using male cats. The changes of penile length, diameter, erectic periods and histological profiles of corpus cavernosum and corpus spongiosum were observed with blood testosterone levels. In conclusion, dose-dependent and significant increase of penile length, diameter, erectic periods and blood testosterone levels were detected in the Gamigyuibitang-dosing groups compared to other groups. In addition, it is also demonstrated that the increasement of congestion of blood vessels and dilation of connective tissues, and decreasement of adipocytes in the corpus cavernosum and/or corpus spongiosum of the Gamigyuibitang-dosing groups. According to these results, it is considered that Gamigyuibitang has some augmentation effect against to apomorphine HCI inducing penile erection and it also suggested that Gamigyuibitang has favorable effect to treatment of erectic dysfunctions induced by p,p-DDE.

• Archives of Pharmacal Research
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• 제8권3호
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• pp.177-186
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• 1985

Effect of food on the absorption characteristics of oral rifampicin was studied in the fasted rats. Rifampicin dissolved in a new cosolvent was also injected to the rats intravenously, and the pharmacokinetic analysis was performed to explain the effect of food on the gastrointestinal absorption of rifampicin. Rifampicin was absorbed rapidly and completely in the fasting state. Food had a profound effect on the gastrointestinal absorption of rifampicin, i. e., bioavailability and the extent of absorption were decreased to less than one-third of the fasting state in the postprandial state. Food seemed to imhibit the absorption and reabsorption of rifampicin in the gastrointestinal tract, but not the absorption rate constant. Hepatobiliary excretion seemed to be the major route of elimination, since the renal clearance accounted for only 8 % of the systemic clearance. Nevertheless, first-pass effect was negligibly small and most of rifampicin absorbed could reach systemic circulation. Serum concentration change of oral rifampicin on multiple dosing differed markedly in the fasting and postprandial state, which suggested the need of careful adjustment of dosage regimen in both states.

• Biomolecules & Therapeutics
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• 제5권1호
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• pp.100-105
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• 1997

DW-166HC ($^{166}$Holmium-chitosan) is a complex of $^{166}$Ho, $\beta$- and $\gamma$-ray emitter, and chitosan, a polymer of glucosamine, with radiotherapeutic potential. The current study was performed to determine the acute toxicities of $^{165}$Ho-chitosan in mice by two different routes of administration. The both sex mice were given a single intravenous bolus injection of $^{165}$Ho-chitosan complex at doses of 12, 10, 6, 5 and 4 mg/kg or subcutaneous administration at doses of 600, 500, 400 and 300 mg/kg. Chitosan was dosed to control animals as 16 and 800 mg/kg, intravenously and subcutaneously, respectively. The doses of $_{165}$Ho-chitosan complex were expressed as $_{165}$holmium nitrate pentahydrate and the ratio of $^{165}$Ho$(NO_3)_3$).$5H_2O$ to chitosan was 3/4 Severe convulsion and respiratory failure were followed by death within 10 min after intravenous dosing. Transient unilateral hindlimb hypokinesias were found in two mice of 5 mg/kg dosing group during the study period. No abnormalities were observed during the necropsy of survived animals in intravenous dosing group. Only one male animal was found dead in 500 mg/kg subcutaneously dosed group. Alopecia with or without cutaneous ulcer were found in most mice including control animals. During necropsy, omental adhesion was observed in all dose ranges and enlarged spleen was found in several animals including control group. It is suggested that the acute intravenous >).$LD_{50}s$ for male and female mice were 4.90 and 6.03 mg/kg, respectively. The lowest lethal dose in male was 500 mg/kg by subcutaneous administration.

• 대한환경공학회지
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• 제36권7호
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• pp.483-491
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• 2014

본 연구에서는 강화된 TP 처리를 위해, 처리해야 할 인 농도에 대한 응집제 최적 주입 비율을 보다 손쉽게 결정하고 조절할 수 있는 실시간 자동제어가 가능한 응집제 주입량 최적제어 시스템(M-COS)을 구성하였으며, 실제 하수처리장 현장실험을 통하여 유량과 수질 변동에 따른 현장 적용성을 검토하였다. 현장적용은 1월말(Period 1), 4월초(Period 2), 5월 중순(Period 3)의 각 시기에 M-COS가 설치된 pilot plant에서 운전?평가되었다. 그 결과, 수질에 따른 능동적 대처가 가능한 M-COS에 비해 대조군의 경우 과량으로 주입된 경우가 많이 발생하여, M-COS에 의한 응집제 절감률은 각 기간 동안 10.4%, 15.3%, 9.0%로 평균 11.6%가 절감되는 것으로 평가되었다. 또한, 응집제 주입에 따른 구입비, 슬러지 발생량, 슬러지 처리비용, 처리용량($1,000,000m^3/d$)을 반영한 처리비용 증가액을 예측하였다. 예측된 M-COS 실험군의 처리비용 증가액은 대조군 대비 각각 13.8%, 20.0%, 11.4%로 평균 15.0%의 비용절감 효과가 나타나, 현장적용이 가능함을 판단할 수 있었다.

• Journal of Yeungnam Medical Science
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• 제10권2호
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• pp.409-416
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• 1993

이상에서와 같이 lithium치의 측정에 있어서 본 병원에서 기존 이용하던 AAS법이나 ISE법 모두 정밀도나 직선성 평가에 있어 비교적 좋았으나, 정밀도(재현성)에 있어서 ISE법이 AAS법보다 더 우수한 것으로 나왔고 ISE법의 경우 측정방법이 매우 간편하였다. 그러나 ISE법에 의한 혈중 측정치가 AAS법에 의한 것보다 다소 높게 나타났으며, ISE법이 AAS법에 비하여 분석 최하한치가 더 높아 예민도는 상대적으로 낮았다.

• 대한수의학회지
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• 제31권4호
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• pp.367-379
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• 1991

The purpose of this study was to investigate the effect of antioxidants (vitamin E, selenium, and coenzyme $Q_{10}$) on the bleomycin-induced pulmonary lesions in male rats. Sprague-Dawley male rats were divided into 4 treatment groups ($T_1$, $T_2$, $T_3$, $T_4$) and 4 control groups ($C_1$, $C_1$, $C_3$, $C_4$). The treatment groups of rats weie given a single intratracheal dose of bleomycin (1.5 units/rat) and control groups of rats were given a single intratracheal dose of normal saline (0.15ml/rat). The rats in the $T_1$ group and $C_1$, group were dosed with normal saline (0.5ml/kg/day), the rats in the $T_2$ group and $C_2$ group were dosed with vitamin E (50mg/kg/day), the rats in the $T_3$ group and $C_3$ group were dosed with sodium selenite (3mg/kg/day) and the rats in the $T_4$ gronp and $C_4$ group were dosed with coenzyme $Q_{10}$ (2.5mg/kg/day) intraperitoneally for 7 days or 14 days, respectively. Animals were killed at 7th and 14th day after dosing with bleomycin or saline. The results obtained were as follows: 1. Lung wet weight of treatment groups of rats was increased significantly while body weight gain of them was decreased significantly in comparison with that of control groups of rats (p<0.01). 2. The ratio(%) of lung wet weight to final body weight of treatment groups of rats was increased significantly in comparison with that of control groups of rats (p<0.01). 3. The main histopathological findings of lungs observed in rats at 7th day after dosing with bleomycin were proliferation of the type II alveolar epithelial cells and fibroblasts, increased invading of macrophages into lesions, round cell infiltration and perivascular edema. 4. Lung fibrous tissues were markedly increased in rats observed at 14th day after dosing with bleomycin. 5. Pumonary lesions observed in rats dosed with bleomycin and antioxidants(vitamin E, selenium, coenzyme $Q_{10}$) were not significantly different from those of rats given bleomycin alone.

• Asian Pacific Journal of Cancer Prevention
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• 제17권4호
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• pp.1903-1907
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• 2016

Background: Studies of effects of IL-1 polymorphisms, CYP2C19 genotype together with antibiotic resistance for H. pylori eradication are rare worldwide. The present study was designed to evaluate efficacy of 10-day sequential therapy (SQT) and 14-day standard triple therapy (STT) with four- times-daily dosing of amoxicillin for H. pylori eradication related to these important host and bacterial factors in Thailand. Materials and Methods: This prospective randomized study was performed during March 2015 to January 2016. H. pylori infected gastritis patients were randomized to receive 10-day sequential therapy and 14-day standard triple therapy. CYP2C19 genotyping, IL1 polymorphism (IL-1B and IL-1RN genotypes) and antibiotic susceptibility tests were performed in all patients. 13C-UBT was conducted to confirm H. pylori eradication at least 4 weeks after treatment. Results: A total of 100 patients (33 males and 67 females, mean age=51.1 years) were enrolled. Eradication rate by PP analysis was 97.9% (47/48) with the 10-day SQT regimen and 87.8% (43/49) with 14-day STT regimen (97.9% vs 87.8%; p-value=0.053). Antibiotic susceptibility testing demonstrated 45% resistance to metronidazole, 14.8% to clarithromycin, and 24.1% to levofloxacin. CYP2C19 genotyping revealed 44.9% RM, 49% IM and 6.1% PM. IL-1B and IL-1RN genotypes were demonstrated as 21.4% for CC, 48.1% for TC, 36.8% for TT, 72.7% for 1/1, and 21.2% for 1/2 genotypes, respectively. The 10-day SQT regimen provided 100% eradication in patients with clarithromycin or dual clarithromycin and levofloxacin H. pylori resistant strains. Moreover, the 10-day SQT regimen resulted in a 100% eradication rate in all patients with CYP2C19 genotype RM and almost type of IL-1B (TC and TT) and IL1-RN genotypes ( 1/2 and other). Conclusions: Treatment with 10-day sequential therapy is highly effective for H. pylori eradication regardless of the effects of clarithromycin resistance, dual clarithromycin and levofloxacin resistance, CYP2C19 genotype, IL-1B and IL1-RN genetic polymorphisms and can be used as effective first line therapy in Thailand.