• The Korean Journal of Physiology and Pharmacology
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• 제21권1호
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• pp.45-54
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• 2017

Our study aims to determine the metabolism and excretion of novel pulmonary-targeting docetaxel liposome (DTX-LP) using the in vitro and in vivo animal experimental models. The metabolism and excretion of DTX-LP and intravenous DTX (DTX-IN) in New Zealand rabbits were determined with ultra-performance liquid chromatography tandem mass spectrometry. We found DTX-LP and DTX-IN were similarly degraded in vitro by liver homogenates and microsomes, but not metabolized by lung homogenates. Ultra-performance liquid chromatography tandem mass spectrometry identified two shared DTX metabolites. The unconfirmed metabolite $M_{un}$ differed structurally from all DTX metabolites identified to date. DTX-LP likewise had a similar in vivo metabolism to DTX-IN. Conversely, DTX-LP showed significantly diminished excretion in rabbit feces or urine, approximately halving the cumulative excretion rates compared to DTX-IN. Liposomal delivery of DTX did not alter the in vitro or in vivo drug metabolism. Delayed excretion of pulmonary-targeting DTX-LP may greatly enhance the therapeutic efficacy and reduce the systemic toxicity in the chemotherapy of non-small cell lung cancer. The identification of $M_{un}$ may further suggest an alternative species-specific metabolic pathway.

• Archives of Pharmacal Research
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• 제25권6호
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• pp.969-972
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• 2002

The alteration in the pharmacokinetic behaviors of organic cations (OCs) in rats during acute inflammation (AI) was investigated. AI was induced by an intraperitoneal injection of lipopolysaccharide (LPS, 5 mg/kg) 24 hr prior to the start of pharmacokinetic studies. Tributylmethylammonium (TBuMA) was selected as a model OC since it is largely excreted into bile, and is neither metabolized nor binds to proteins in the body. When TBuMA was administered intravenously to AI rats at a dose of 6.6 $\mu$mole/kg, the AUC was increased, while biliary excretion (i.e., cumulative amount and apparent clearance) was decreased compared to normal rats. When TBuMA was administered intravenously to AI rats at a constant rate (i.e., a bolus injection at a dose of 1.5 $\mu$mole/kg followed by a constant infusion at a rate of 1.5 $\mu$mole/kg/hr for 165 min), steady-state concentrations of plasma and liver concentrations of TBuMA were increased significantly, while in vivo hepatic uptake (amount) and canalicular excretion (clearance) were decreased. These results are consistent with a hypothesis in which both the sinusoidal uptake of TBuMA into hepatocytes via the OCT1 and the canalicular excretion of the compound from hepatocytes via the P-gp are decreased by LPS-induced AI.

• Journal of Pharmaceutical Investigation
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• 제36권2호
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• pp.137-142
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• 2006

A bioequivalence of Daewoong $Alendronate^{TM}$ (Daewoong Pharmaceutical Co., Ltd., Korea) and $Fosamax^{TM}$ tablets (MSD Korea) was evaluated according to the guideline of Korea Food and Drug Administration (KFDA). A single 70 mg dose of sodium alendronate of each medicine was administered orally to 56 healthy male volunteers. This study was performed in a $2\;{\time}\;2$ crossover design. Concentrations of alendronate in the urine were monitored by a high-performance liquid chromatography (HPLC). $A_{et}$ (cumulative urinary excreted amount from time 0 to last sampling interval) was calculated by the accumulation of the urinary excreted alendronate. $U_{max}$ (maximum urinary excretion rate) and $T_{max}$ (time to reach $U_{max}$) were compiled from the urinary excretion rate - time data. Analysis of variance was performed using logarithmically transformed $A_{et}$ and $U_{max}$. No significant sequence effect was found for all of the bioavailability parameters. The 90% confidence intervals of the $A_{et}$ and $U_{max}$ for Daewoong $Alendronate^{TM}/Fosamax^{TM}$ were 0.89-1.12 and 0.82-1.02, respectively. This study demonstrated the bioequivalence of Daewoong $Alendronate^{TM}$ and $Fosamax^{TM}$ with respect to the rate and extent of absorption.

• 대한방사선기술학회지:방사선기술과학
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• 제39권2호
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• pp.237-246
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• 2016

방사성동위원소 사용시설 내/외 화장실 표면 방사선량률과 공간 방사선량률을 측정하여 화장실을 이용하는 환자 이외 방사선작업종사자 및 환자보호자 등의 안전성을 확보하고 방사선 방어 연구에 대한 기초 자료로 제시 하고자 한다. 2014년 5월 1일부터 7월 31일까지 인천광역시 소재 종합병원 방사성동위원소 사용시설 내/외 화장실 4곳의 공간 방사선량률과 작업 전/후 표면 방사선량률을 각각 측정하였다. 의료기관별 방사성동위원소 사용시설 내 화장실 이용 실태조사 결과 환자뿐만 아니라 환자 보호자, 일부 방사선 작업종사자까지 다양하게 이용하고 있었다. 화장실 내 공간 방사선량률 측정 결과 핵의학적 검사 중 감마촬영실을 이용하는 화장실의 누적 공간선량률은 8.86 mSv/hr으로 가장 높게 측정되었고, 방사성옥소 치료실 화장실은 7.31 mSv/hr, PET촬영실 화장실 2.29 mSv/hr, 외래 진료과 화장실 0.26 mSv/hr으로 각각 측정되었다. 방사성동위원소 작업 전/후 화장실 내 표면 방사선량률을 측정한 결과 대부분 환자 배설물이 직접 닫는 변기 앞에서 표면 방사선량률이 가장 높게 측정되었고, 화장실 내 중앙, 입구 순으로 측정되었다. 개봉선원은 물리적 반감기가 짧고 에너지가 낮아 비교적 안전하여 방사선 관리구역에서 안전하게 사용되고 있다. 그러나 저에너지 이며 짧은 반감기의 방사선원이라 하더라도 환자에게 투여되면 그 이후 환자는 움직이는 방사선원이 되며 환자가 이용하는 장소는 배설물에 의한 방사선 오염 장소가 된다. 따라서 효과적으로 유효선량을 최소화하고 불필요한 피폭선량을 줄이기 위해 방사성동위원소 투여 후 충분한 수분 섭취를 독려하여 생물학적 반감기를 낮추고, 물리적 반감기가 허용 선량이하로 될 때까지 주변인은 환자로부터 가급적 멀리 떨어져 생활하도록 권고되어야 한다.

• Archives of Pharmacal Research
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• 제26권11호
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• pp.979-983
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• 2003

The pharmacokinetic of tolbutamide was studied after the oral administration to normal rabbits or rabbits with mild to medium folate-induced renal failure. The plasma concentrations of tolbutamide were significantly elevated (p<0.05) during 9 to 24 h in rabbits with mild or medium folate-induced renal failure. Consequently, the area under the plasma concentration-time curves (AUC) was significantly higher in mild (p<0.05) and medium (p<0.01) folate-induced renal failure rabbits (i.e., 2906 $\mu$g/mL$.$h for mild renal failure and 4074 $\mu$g/mL$.$h for moderate renal failure) than that in normal rabbits (i.e., 2295 $\mu$g/mL$.$h). The cumulative urinary excretion of tolbutamide was significantly depressed (p<0.05) in medium folate-induced renal failure rabbits (i.e., 3.3 mg) compared with that in normal rabbits (i.e., 5.9 mg). The elimination rate constant (Kel) of tolbutamide was significantly decreased in medium renal failure rabbits (i.e., 0.027 $h^{-1}$) than that in normal rabbits (i.e., 0.044 $h^{-1}$ ); As a result, the terminal half-life of tolbutamide in medium folate-induced renal failure rabbits (i.e., 25.5 h) was significantly longer (p<0.01) than that in normal rabbits (i.e., 15.7 h). The change in pharmacokinetic parameters is consistent with the hypothesis that the alteration is mediated by the depressed metabolic elimination of the drug by the induction of renal failure. Therefore, these observations indicated that the dosage adjustment may be necessary for tolbutamide in patients with renal insufficiency.

• Toxicological Research
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• 제16권3호
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• pp.211-219
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• 2000

The therapeutic effect of AS2-006A, a derivative of asiaticoside, has been studied and is being developed as a new wound-healing agent. In the present study, the general pharmacological effects on 1) central nervous system, 2) autonomic nervous system, 3) respiratory system, 4) gastrointestinal system. 5) cardiovascular system. and 6) urinary system were assessed in experimental animals and in in vitro models. 1. In vivo animal study: External applications of the 1 % gel ointment of AS2-006A to rats at the doses of 200. 600 or 2000 mg/kg body weight showed no observable pharmacological effects. The effects on the central nervous system were assessed by observation of behavior, hexobarbital-induced sleeping time, pentetrazole-induced convulsion assay, body temperature measurements, and observations on spontaneous activity and catalepsy. The gel ointment exhibited no effects on the cardiovascular system (i.e. blood pressure and heart rate), renal physiology (i.e. urine volume and electrolytes excretion) and gas-trointestinal physiology (i.e. intestinal charcoal propulsion and gastric mucosal irritation). 2. In vitro experiments: The effects of AS2-006A on the physiology of smooth and cardiac muscles were assessed. Muscle contractions were isotonically and isometrically measured in organ chambers using a physiograph. Cumulative additions of AS2-006A (10$^{-9}$ -10$^{-5}$ M) induced no changes in the tension of isolated guinea pig ileum and tracheal muscles. AS2-006A only slightly increased contractility of rat atrial and papillary muscles at 10$^{-2}$ M, which was not statistically different from control. These data showed that the gel ointment of AS2-006A could be externally applied as a wound-healing agent with no potential side effects.