• 대한예방한의학회지
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• 제18권2호
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• pp.89-100
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• 2014

Objective : The co-administration effects of Gongjindan (GJD) on the pharmacokinetics (PK) of sorafenib were observed as a process of the comprehensive and integrative medicine. Methods : After sorafenib treatment, GJD was administered within 5 min. The plasma were collected at 30min before administration, 30min, 1, 2, 3, 4, 6, 8 and 24hrs after end of GJD treatment, and plasma concentrations of sorafenib were analyzed using LC-MS/MS methods. PK parameters of sorafenib ($T_{max}$, $C_{max}$, AUC, $t_{1/2}$ and $MRT_{inf}$) were analysis as compared with sorafenib single administered rats. Results : The absorption of sorafenib were significantly increased at 30min, 1, 6 and 6hrs after co-administration with GJD as compared with sorafenib single treated rats. Accordingly, the $AUC_{0-t}$ (47.20%) of sorafenib was significantly increased but $t_{1/2}$ (-30.63%) and $MRT_{inf}$ (-34.11%) in co-administered rats were non-significantly decreased. These findings are considered as direct evidences that GJD increased the oral bioavailability of sorafenib through increase of the absorption, when they co-administered within 5min. Conclusion : Based on the results, co-administration of GJD increased the oral bioavailability of sorafenib through increase of the gastrointestinal absorption. It is considered that the more detail pharmacokinetic studies should be tested to conclude the effects of GJD on the pharmacokinetics of sorafenib, when they were co-administered, like the effects after co-administration with reasonable intervals considering the $T_{max}$ of sorafenib (about 3.5hr-intervals) and after repeated co-administrations.Hence, concomitant uses of GJD with sorafenib may require close monitoring for potential drug interactions.

• 공업화학
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• 제32권5호
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• pp.509-515
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• 2021

본 연구는 생체적합성 및 생분해성의 특성을 갖는 PLGA (poly lactic-co-glycolic acid)를 이용하여 이중(w/o/w) emlusion과 유화 용매-증발 기법을 통해 PLGA 나노입자(PNP)를 제조하였고, 이에 키토산을 전하 상호작용을 통해 키토산이 코팅된 PLGA 나노입자(CPNP)를 제조하여 입자의 안정성과 생체이용률을 극대화할 수 있는 경구 투여용 약물 전달체로 사용 가능성을 입증하고자 하였다. CPNP의 화학적 구조는 ¹H-NMR 및 FT-IR을 통해 분석하였으며, 모든 특성 피크가 나타남으로써 성공적으로 제조되었음을 확인하였다. 또한, CPNP의 입자 크기, 제타 전위 및 형태학적 이미지는 DLS와 TEM을 이용하여 각각 분석하였으며, TGA를 통해 CPNP의 열적 분해 거동을 관찰하였다. 또한, CPNP의 세포 독성은 HEK293 및 L929 세포에서 MTT assay를 수행하여 확인하였고, 모든 농도에서 70% 이상의 세포 생존율을 확인함으로써 독성이 없음을 입증하였다. 이러한 결과를 통해 본 연구에서 개발된 CPNP가 경구용 약물 전달체로써 사용 가능성이 있음을 제안한다.

• Nuclear Engineering and Technology
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• 제55권4호
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• pp.1460-1467
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• 2023

A robust approach was conducted to determining the absolute oral bioavailable (f_ab) fractions of ²³⁸U and ²³²Th in rats exposed to contaminated soil along with their hematotoxicity and nephrotoxicity. The soil sample is the International Atomic Energy Agency-312 (IAEA-312) certified reference material, whereas blood, bones, and kidneys of in vivo female Sprague-Dawley (SD) rats estimate ²³⁸U- and ²³²Th-f_ab fractions post-exposure. We predict the bioavailable concentration (C_ab) and f_ab values of ²³⁸U and ²³²Th after acute soil ingestion. The blood ²³⁸U (0.750%) and ²³²Th (0.028%) reach their maximum f_ab values after 48 h. The ²³⁸U (f_ab: 0.169-0.652%) accumulates mostly in the kidney, whereas the ²³²Th (f_ab: 0.004-0.021%) accumulates primarily in the bone. Additionally, ²³⁸U is more bioavailable than ²³²Th. Post 48 h acute ingestion demonstrates noticeable histopathological and hematological alterations, implying that intake of ²³⁸U in co-contaminated soil can lead to erythrocytes and proximal tubules damage, whereas, ²³²Th intake can harm erythrocytes. Our study provides new directions for future research into the health implications of acute oral exposures to ²³⁸U and ²³²Th in co-contaminated soils. The findings offer significant insight into the utilization of in vivo SD rat testing to estimate ²³⁸U and ²³²Th bioavailability and toxicity in exposure assessment.

• Asian Pacific Journal of Cancer Prevention
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• 제15권19호
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• pp.8377-8382
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• 2014

Background: Oral squamous cell carcinoma (OSCC) is the sixth most common malignancy worldwide. Cancer development and progression require inactivation of tumor suppressor genes and activation of proto-oncogenes. The well recognized mechanism of action demonstrated for chemotherapeutic agents is induction of apoptosis via reactivation of p53. In this context, we evaluate the efficacy of IV and oral routes of our novel PH and temperature sensitive doxorubicin-methotrexate-loaded nanoparticles (DOX-MTX NP) in affecting p53 profile in an OSCC rat model. Methods: In this study, 120 male rats were divided into 8 groups of 15 animals each. The new formulated DOX-MTX NP and free doxorubicin were IV and orally given to rats with 4-nitroquinoline-1-oxide induced OSCC. Results: Results showed that both DOX and DOX-MTX-NP caused significant increase in mRNA levels of P53 compared to the untreated group (p<0.000). With both DOX and DOX-MTX NP, the IV mode was more effective than the oral (gavage) route (p<0.000). Surprisingly, in oral mode, p53 mRNA was not affected in DOX treated groups (p>0.05), Nonetheless, both IV and oral administration of MTX-DOX NP showed superior activity (~3 fold) over free DOX in reactivation of p53 in OSCC (p<0.000). The effectiveness of oral route in group treated with nanodrug accounts for the enhanced bioavailability of nanoparticulated DOX-MTX compared to free DOX. Moreover, in treated groups, tumor stage was markedly related to the amount of p53 mRNA (p<0.05). Conclusion: Both oral and IV application of our novel nanodrug possesses superior activity over free DOX-in up-regulation of p53 in a OSCC model and this increase in p53 level associated with less aggressive tumors in our study. Although, impressive results obtained with IV form of nanodrug (-21 fold increase in p53 mRNA level) but both forms of nanodrug are effective in OSCC, with less toxicity normal cells.

• Biomolecules & Therapeutics
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• 제11권3호
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• pp.163-168
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• 2003

Pharmacokinetics of eupatilin (an active components of $Stillen^{\circledR}$, a new antigastritic agent) were investigated after both intravenous and oral administration at a dose of 30mg/kg to rats. After intravenous administration, the plasma concentrations of unchanged eupatilin declined rapidly with a mean terminal half-life of 0.101 h. Eupatilin was eliminated fast in rats; the total body clearance was 121 mL/min/kg. Eupatilin was mainly metabolized in rats; the percentage of intravenous dose of eupatilin excreted in 24 h urine and feces as unchanged eupatilin was only 2.5 and 0.919％, respectively. Eupatilin was mainly metabolized to form its glucuronide conjugate; after intravenous administration, 15.9 and 51.7％ of intravenous dose was excreted in 24 h urine and feces, respectively, as eupatilin plus its glucuronide. After oral administration, the absolute bioavailability was only 3.86％ based on $AUC_{0-24h}$ of eupatilin plus its glucuronide. Approximately 68.5％ of oral dose was not absorbed from the entire gastrointestinal tract. Therefore, it could be concluded that the superior effect of eupatilin in experimental animal models of gastric ulcer and inflammatory bowel disease after oral administration could be due to the local action of eupatilin. Further pharmacokinetic studies to elucidate the local action of eupatilin are required.

• Journal of Pharmaceutical Investigation
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• 제35권6호
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• pp.471-481
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• 2005

In Korea, generic drug and bioequivalence test are the hot issues since a new medical system of separation of dispensary from medical practice was started in 2000. The KFDA(Korea FDA) had revised several times ${\ulcorner}Guidance\;for\;bioequivalence\;test{\lrcorner}$. In vitro dissolution test has been extensively used as a quality control tool for solid oral dosage forms. In an effort to minimize unnecessary human testing, in vitro/in vivo correlations (IVIVC) between in vitro dissolution and in vivo bioavailability are increasingly becoming an integral part on extended release drug product development. The recently published US guidance, ${\ulcorner}Extended\;release\;oral\;dosage\;forms\;:\;development,\;evaluation,\;and\;application\;of\;in\;vitro/in\;vivo\;correlations{\lrcorner}$ will be helpful for us to make our own guideline.

• Archives of Pharmacal Research
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• 제19권5호
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• pp.359-367
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• 1996

The pharmacokinetics of LB20304 was investigated following intravenous (IV) and oral administration to rats and dogs. Additionally, in vitro metabolism and serum protein binding studies were also conducted. The total body clearance, apparent volume of distribution, terminal half-life, and extent of bioavailability were 21.8 ml/min/kg, 2265 ml/kg, 93.6 min, and 30.8% for rats; and 7.95 ml/min/kg, 4144 ml/kg, 363 min, and 81.1% for dogs, respectively. LB20304 was stable in the liver microsome containing NADPH generating system and its serum protein binding was 58.5-65.8% for rats, 19.1-29.6% for dogs, and 56.9-59.6% for humans. Its tissue concentration levels in lever, stomach, small intestine, and kidney were 9.5 to 26.1 times greater than plasma level, but the concentration in testis was quite low and that in brain was negligible in rats. The 48 hr urinary recovery of the dose was 44% for IV dosing and 14% for oral dosing, shereas the 48 hr biliary recovery of the dose was 6.4% for IV dosing and 4.5% for oral dosing in rats. In summary, the pharmacokinetic properties of LB20304 were characterized by its good oral absorption, long plasma half-life, and good tissue distribution.

• 분석과학
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• 제34권5호
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• pp.193-201
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• 2021

We have demonstrated a sensitive analytical method of measuring oleracone D in mouse plasma using a liquid chromatography-tandem mass spectrometry (LC-MS/MS). Oleracone D and oleracone F (internal standard) in mouse plasma samples were processed using a liquid-liquid extraction method with methyl tertbutyl ether, resulting in high and reproducible extraction recovery (80.19-82.49 %). No interfering peaks around the peak elution time of oleracone D and oleracone F were observed. The standard calibration curves for oleracone D ranged from 0.5 to 100 ng/mL and were linear with r² of 0.992. The inter- and intra-day accuracy and precision and the stability fell within the acceptance criteria. The pharmacokinetics of oleracone D following intravenous and oral administration of oleracone D at doses of 5 mg/kg and 30 mg/kg, respectively, were investigated. When oleracone D was intravenously injected, it had first-order elimination kinetics with high clearance and volume of distribution values. The absolute oral bioavailability of this compound was calculated as 0.95 %, with multi-exponential kinetics. The low aqueous solubility and a high oral dose of oleracone D may explain the different elimination kinetics of oleracone D between intravenous and oral administration. Collectively, this newly developed sensitive LC-MS/MS method of oleracone D could be successfully utilized for investigating the pharmacokinetic properties of this compound and could be used in future studies for the lead optimization and biopharmaceutic investigation of oleracone D.

• 한국임상약학회지
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• 제15권1호
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• pp.50-54
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• 2005

The purpose of this study is to investigate the effect of aspirin on the pharmacokinetics of pranoprofen by oral coadministration of pranoprofen (5 mg/kg) with aspirin (5, 10 and 20 mg/kg) in Sprague-Dawley rats. After oral coadministration of pranoprofen with aspirin, the area under the plasma concentration-time curves (AUC) of pranoprofen was increased significantly by 10 mg/kg (p<0.05) and 20 mg/kg (p<0.01) of aspirin coadministration, and peak concentrations ($C_{max}$) of pranoprofen was increased significantly by coadministration of 20 mg/kg aspirin (p<0.05) compared to pranoprofen alone. Relative bioavailabilities (RB${\%}$) of pranoprofen in coadmistration were higher (from 1.42 to 1.67 fold) than control. The half-lives ($t_{1/2}$) of pranoprofen in coadministration were increased significantly (p<0.05) by 20-mg/kg aspirin. Based on these results, we might be considered that the pharmacokinetics of pranoprofen would be affected by coadministration of aspirin, by inhibit its metabolism in the liver and the tubular secretion of the kidney with the same acidic property. It should take into consideration in dosage regimen of pranoprofen when coadministration of pranoprofen with aspirin in treatment of rheumatoid arthritis.

• Journal of Pharmaceutical Investigation
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• 제35권3호
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• pp.157-163
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• 2005

The pellets with multiple drug release system (MDRS) of Diltiazem. HCl which consist of immediate drug release layer, drug reservoir layer and controlled release rate membrane, were prepared by using CF-Coater. As main factors for more effective MDRS of Diltiazem. HCl, ethylcellulose was used for the controlling drug release rate, and diethylphthalate was used for plasticizer, respectively. In vitro evaluation study was performed by comparative dissolution test between our test MDRS and reference Diltiazem. HCl preparation. The physical tests were performed using FT-IR and SEM. In vivo evaluation was also performed by observing the behavior of a plasma drug concentration after oral administration. The bioavailability was determined by analyzing the blood sample after oral administration to healthy, male volunteers once a day. As a result, there were no significant differences in bioequivalence parameters $(AUC_{\infty},\;C_{max},\;t_{1/2})$ between two systems. It might be concluded that our MDRS of Diltiazem. HCl could be an alternative delivery system to reference drug preparation.