• Biomolecules & Therapeutics
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• 제8권4호
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• pp.332-337
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• 2000

Physicochemical properties of aspalatone (acetylsalicylic acid maltol ester, AM), which has been recently found to have an antithrombotic effect, were studied in terms of solubility, dissolution, partition coefficient (Pc) and stability. The solubility of AM at 37$^{\circ}C$ was about 1.2 mg/ml and the P$_{c}$ value for n-octanol/water and chloroform/water was 11.4 and 382.6, respectively. Dissolution rates of AM at pH 1.2 and 6.8 were more than 80% within 30 min. The degradation of AM followed apparent first-order kinetics, and was dependent on temperature, pH and ionic strength. From the pH-rate profile, the optimal pH was found to be at around 4.0. Half-lives at pH 1.2 and 6.8 were 33.5 and 44.4 hr, respectively. The degradation rate of AM at pH 1.2 was somewhat faster than that of aspirin, but at pH 7.0, the degradation rate of AM was slower than that of aspirin.n.

• Macromolecular Research
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• 제11권4호
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• pp.283-290
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• 2003

Organic drugs including aspirin, omeprazole, and naproxen with three different levels of octanol/water partition coefficient were examined for their release behavior from the amphiphilic PCL-b-PEO-b-PCL (PCEC) matrix. Scanning electron micrograph (SEM) of PCEC illustrated a well defined two-phase morphology consisted of dispersed poly(ethylene oxide) (PEO) domain and continuous polycaprolactone (PCL) phase. Differential scanning calorimetry (DSC) and X-ray diffractometry (XRD) experiments veri tied that three model drugs are dissolved as a molecular dispersion in PCEC matrix. The release of hydrophilic aspirin closely followed the water absorption profile of the matrix indicating that its major fraction is present in PEO domain. However, substantial amount of aspirin present in less hydrophilic region displayed discontinuous biphasic release pattern. In the case of omeprazole with intermediate hydrophobicity consistent release behavior was observed for a period of 24 hrs after the rapid liberation of ca. 10% of the drug presumably partitioned in PEO phase. It was ascribed to the fact that the progressive hydration of PCEC matrix gradually increased the chance of drug/water exposure to compensate the exhaustion of device. Naproxen with the highest octanol/water distribution coefficient among three model drugs exhibited a limited release of 35% for 24 hrs. Finally, hydroxypropyl methylcellulose phthalate (HPMCP)/PCEC blend matrix demonstrated an accelerated and quantitative release of hydrophobic naproxen by generating high porosity and thereby expanding polymer/water interface.

• 약학회지
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• 제47권5호
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• pp.331-338
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• 2003

A butyrolactone ester of cefazolin (CFZ-BTL) was synthesized by the esterification of cefazolin (CFZ) with $\alpha$-bromo-${\gamma}$-butyrolactone. The synthesis was confirmed by the spectroscopic analysis. The CFZ-BTL was more lipophilic than the CFZ when assessed by n-octanol/water partition coefficients at various pH. The CFZ-BTL itself did not show any antimicrobial activity in vitro, but after oral administration of CFZ-BTL to rabbits, exerted significant anti-microbial activity in serum samples when measured by the inhibion zone method in nutrient agar plates, due to conversion of CFZ-BTL to an active metabolite, probably CFZ, in the body. The CFZ-BTL was also converted into CFZ as confirmed by in vitro incubation study, with tissue homogenates (liver, blood and intestine) of rabbits. The liver showed the fastest conversion rate, probably via the hydrolysis mechanism. In vivo metabolism of CFZ-BTL to CFZ was also confirmed in vivo serum samples by HPLC. The oral bioavailability of CFZ-BTL in rabbits was 1.6-fold increased when compared to CFZ, resulting from followed by enhanced lipophilicity increased passive absorption in the intestine.

• Environmental Analysis Health and Toxicology
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• 제21권2호
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• pp.93-102
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• 2006

Methyl tert-butyl ether (MTBE), an octane booster that is added to the reformulated gasoline, has been a widespread contaminant in aquatic ecosystem. MTBE is a recalcitrant pollutant having low biodegradability. Due to its higher water solubility and low octanol-water partition coefficient, it can be rapidly transported to the surrounding water environment. Also, MTBE is a known animal carcinogen, and is classified as a possible human carcinogen by U. S. Environmental Protection Agency. The adverse effect of MTBE to aquatic biota was widely reported. In Korea, the recent detection of MTBE in groundwater near gasoline filling stations has drawn concern to public health and ecosystem. To address this concern, the effect of MTBE to human health and ecosystem was discussed in this review. Also, ecotoxicity data of MTBE for fish, invertebrates, and algae were extensively compared to estimate the hazard concentration 5($HC_5$) of MTBE as a screening level.

• 약학회지
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• 제46권3호
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• pp.168-173
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• 2002

The physicochemical properties of aloesin, which has been recently found to reduce renal toxicity induced by cis-platin, were studied including solubility, partition coefficient ( $P_{c}$ ), osmolality, and stability. The solubility of aloesin was about 500 mg/mι, and the $P_{c}$ value for n-octanol/water was 1.01 $\pm$ 0.03. The degradation of aloesin followed the pseudo-first-order kinetics and was dependent on temperature, pH and ionic strength. From the pH-rate profile, the optimal pH was found to be 2.0~3.0. Some metal ions increased the degradation rate in the rank order of M $n^{2+}$ ＞ F $e^{3+}$ ＞ C $u^{2+}$ ＞ F $e^{2+}$. On the other hand, other metal ions such as B $i^{3+}$, $Ba^{2+}$, Z $n^{2+}$, N $i^{2+}$, $Co^{2+}$ and $Mg^{2+}$ did not show the unfavorable effects. After autoclaving, aloesin contents remaining were 81.8~98.8% of initial concentrations depending on pH. The most stable pH was 3.98 in the autoclaving. Osmolality increased linearly as concentration increased.sed.creased.sed.

• 대한환경공학회지
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• 제27권7호
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• pp.690-696
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• 2005

시화호를 대상으로 수계 중 다환방향족탄화수소(PAHs)의 농도와 분포특성을 조사하였다. 용존상과 입자상으로 분리된 물시료와 저질 시료를 분석한 결과 시화호의 상류인 반월지역과 하류인 시화지역의 물 시료 중 PAHs 농도는 각각 $21.9{\sim}49.6\;ng/L$, $19.4{\sim}99.7\;ng/L$로 나타났으며, $85{\sim}90%$ 정도가 용존상에 존재하였다. 또한 저질시료에서는 반월지역이 $51.7{\sim}325\;ng/g-dry$, 시화지역이 $13.4{\sim}72.3\;ng/g-dry$으로 다소 지역적 차이가 있는 것으로 나타났다. 수중 용존상은 저분자와 중간 분자량대 화합물이 주를 이루고 수중 입자상과 저질은 중간 분자량과 고분자량대 화합물이 주를 이루고 있었다. 옥탄올/물 분배계수에 대한 수중 용존상/입자상 분배계수로부터 얻어진 회귀직선의 기울기는 $0.73{\pm}0.12$로 나타났으며, 물/저질 분배계수로부터 얻어진 기울기는 $0.59{\pm}0.10$으로 나타났다. 이러한 결과로부터 저질/물 사이의 분배현상 뿐만 아니라 수중 용존/입자 상 분배 현상도 평형에 도달하고 있지 못한 것을 알 수 있었다.

• Applied Biological Chemistry
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• 제40권1호
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• pp.71-75
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• 1997

농약의 물리화학적 특성에 관한 연구의 일환으로 captafol의 수용성, 가수분해, 증기압, 분배계수를 표준 측정기법 인 미국 EPA와 OECD 방법에 준하여 측정하였다. 수용성은 $25^{\circ}C$ 조건에서 2.24 ppm이었으며, 가수분해에 의한 반감기는 $25^{\circ}C$에서 77.8시간(pH 3.0), 6.54시간(pH 7.0), 0.72시간(p班 8.0)으로 나타나 알칼리 조건에서 불안정한 화합물임을 확인하였다. 산성조건에서의 반감기는 온도에 영향을 받지 않았으나, 중성, 알칼리 조건에서의 반감기는 $40^{\circ}C$에서 매우 짧았다. 가수분해 실험의 표준 대조물질인 diazinon을 이용하여 실험한 결과 본 연구실에서 수행한 가수분해 실험은 적합한 것으로 판정되었다. Captafol은 상온에서 증기압 ($8.27{\times}10^{-9}\;torr,\;20^{\circ}C$)이 높지 않으므로 휘발에 의하여 대기환경에 영향을 미칠 가능성은 없으리라 예상되었고, log P=6.94-(4401.6/T)라는 관계식을 유도할 수 있었다. Captafol은 옥탄올/물 분배계수치가 높아(Kow=1,523) 먹이연쇄를 통한 생물농축의 가능성이 예상되나 가수분해가 빠르기 때문에 비록 captafol이 수계에 노출된다고 하여도 분해가 빠르게 일어나 어류 생체내에 농축되어 인체에까지 영향을 미칠 가능성은 매우 낮을 것으로 사료되었다.

• Applied Biological Chemistry
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• 제40권1호
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• pp.76-79
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• 1997

국내에서 최초로 합성, 개발된 유기인계 살충제인 flupyrazofos(KH-502)의 물리화학적 특성으로 수용성, 가수분해, 증기압, 분배계수를 EPA와 OECD 방법에 준하여 측정하였다. 수용성은 $25^{\circ}C$에서 0.80 ppm으로 낮았고 가수분해 반감기는 $25^{\circ}C$에서 266.5시간(pH 4.0), 180.0시간(pH 7.0), 120.9시간(pH 9.0)으로 알칼리 조건에서 불안정하였으며 $40^{\circ}C$에서는 $25^{\circ}C$보다 $2{\sim}4$배 정도 가수분해가 빠르게 진행되었다. 상은($25^{\circ}C$)에서의 증기압은 $2.81{\times}10^{-5}$ torr로 측정되었고, 다른 두 온도(35, $45^{\circ}C$)에서 증기압을 측정하여 log P=0.673-(1565.4/T)라는 관계식을 구하였다. Flupyrazofos의 상온($25^{\circ}C$)에서의 증기압은 diazinon과 유사한 수준이었고, DDVP보다는 약 1,000배 정도 낮은 수치로 휘발에 의하여 환경에 영향을 미칠 가능성은 낮을 것으로 판단되었다. Flupyrazofos의 옥탄올/물 분배계수치를 보면(log Kow=5.24) 먹이연쇄를 통한 생물농축이 예상되나 비교적 가수분해가 빠르기 때문에 비록 수계에 노출된다고 하여도 그 가능성은 매우 낮을 것으로 사료된다.

• 한국임상약학회지
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• 제8권2호
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• pp.133-138
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• 1998

Phthalimidyl ester of ceftezole (CFZ-PT) was synthesized as a prodrug by esterification of ceftezole (CFZ) with N-bromophthalimide. CFZ-PT was more lipophilic than CFZ when the lipophilicity was assessed by partition coefficients between n-octanol and water at various pH. The pharmacokinetic characteristic of CFZ-PT and CFZ preparations were compared following oral administrations of these compounds to rabbits. CFZ-PT is expected to be metabolized rapidly to CFZ in the body. The metabolism process appears to be hydrolysis of the ester to CFZ, the parent drug of CFZ-PT. In vivo metabolism of CFZ-PT to CFZ was confirmed in rabbit by HPLC analysis. CFZ concentration in the serum samples taken after oral administration of CFZ-PT(equivalent amount of CFZ) were released and higher than those of CFZ. Oral bioavailability of CFZ-PT was 1.9 fold higher than at of CFZ in rabbits because of enhanced lipophilicity and absorption. Finally, it was concluded that CFZ-PT appears useful as a prodrug of CFZ to improve the oral bioavailability of CFZ.

• Journal of Pharmaceutical Investigation
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• 제27권2호
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• pp.125-131
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• 1997

Ethoxycarbonyloxyethyl ester of ceftezole (CFZ-ET) was synthesized as a prodrug by esterification of ceftezole (CFZ) with ethoxycarbonyloxyethyl chloride and was confirmed by spectroscopic analyses. CFZ-ET was more lipophillic than CFZ as assessed by n-octanol and water partition coefficients at various pH. CFZ-ET itself did not show any microbiological activity in vitro, but showed substaintial microbiological activity after oral administration of CFZ-ET, indicating that CFZ-ET is converted to microbiologically active metabolite, probably CFZ, in the body. When CFZ-ET was incubated in blood, liver and intestine homogenates of rabbits, liver homogenate showed the fastest conversion of CFZ-ET. CFZ-ET appears rapidly metabolized in the liver when given orally due to the hydrolysis of the ester to CFZ, the parent drug of CFZ-ET. In vivo metabolism of CFZ-ET to CFZ was confirmed in rabbit by HPLC analysis. CFZ-ET were higher than those in the serum samples taken after oral administration of equivalent amount of CFZ. Oral bioavailability of CFZ-ET was 1.5-fold higher than that of CFZ in rabbits because of enhanced lipophilicity and absorption. Based on these findings, CFZ-ET appears useful as a prodrug of CFZ to improve the oral bioavailability of CFZ.