• Archives of Pharmacal Research
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• 제27권9호
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• pp.973-977
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• 2004

Carvedilol is administered as a racemic mixture of the R(＋)- and S(-)-enantiomers, although they exhibit different pharmacological effects. To investigate the stereoselective pharmacoki-netics, the enantiomeric separation of carvedilol in human plasma was undertaken using capil-lary electrophoresis (CE). Resolution of the enantiomers was achieved using 2-hydoxypropyl-$\beta$-cyclodextrin as the chiral selector. Phosphate buffer (50 mM, pH 4.0) containing 10 mM of 2-hydoxypropropyl-$\beta$-cyclodextrin was used as electrolytic buffer. Achiral separation was carried out with the same electrolytic buffer without chiral selector. Following a single oral administra-tion of 25-mg carvedilol to 11 healthy, male volunteers, stereoselective pharmacokinetic analy-sis was undertaken. The maximum plasma concentrations ( $C_{max}$) were 48.9 and 21.6 ng/mL for (R)-carvedilol and (S)-carvedilol, respectively, determined by the chiral method. The profiles of the plasma concentration of (RS)-carvedilol showed $C_{max}$ of 71.5, 72.2, and 73.5 ng/mL, as determined by the CE, HPLC/FD methods and calculations from the data of the chiral method, respectively.y.y.

• 대한수의학회지
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• 제35권4호
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• pp.683-689
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• 1995

임상적으로 건강한 New Zealand White 종인 수컷 토끼에서 항생제 norfloxacin(NFX)의 체내 동태를 조사하기 위하여 체중 kg당 5mg을 정맥 및 경구 투여하였다. 그 결과 빠른 분포기와 소실기를 갖는 2-콤파트먼트 모델 양상으로 나타났다. 혈장에서의 약물분석은 HPLC로 실시하였는데, 이동상은 acetonitrile/0.01M phosphate buffer/ 10% citric acid 1mM heptane sulfonic acid(10/70/20)이었고, 흡수 파장은 274nm에서 실시하였다. 정맥 투여후, 생물학적 반감기는 3.14시간으로 나타났으며, 분포반감기는 0.38시간으로 빠른 분포를 보여주었다. 최고 혈중농도는 $24.27{\mu}g/ml$로 계산되었으며 청소율은 0.68ml/kg/h로 분석되었다. 경구 투여후, 최고 혈중 농도와 최고 혈중 도달 시간은 $0.86{\mu}g/ml$과 0.43시간으로 각각 계산되었다. 이때의 생물학적 반감기는 3.61시간으로 정맥 투여시와 유의성 있는 차이는 없었으며, 흡수 반감기는 0.17시간으로 빠른 흡수를 보여주었다. 생체이용율은 30%로 나타났으며, 0.2-1.6g/ml인 치료혈중 농도 범위에서 혈장 결합율은 26%로 나타나, 토끼에서 항생요법은 구강 투여시 초기 투여량은 2.71mg/kg이며, 유지 투여량은 12시간마다 2.54mg/kg이 적당한 것으로 분석되었다.

• Journal of Pharmaceutical Investigation
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• 제28권4호
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• pp.215-221
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• 1998

In order to elucidate the fraction of sulfoxidation in the over all in vivo metabolism of chlorpromazine (CPZ), the sulfoxidation of CPZ to chlorpromazine sulfoxide (CPZSO) was studied in rats. CPZ (10 mg/kg) and CPZSO (1 mg/kg) were injected into the rat femoral vein, respectively. And the pharmacokinetic parameters were obtained from the plasma concentration-time profiles of CPZ and CPZSO determined by the simultaneous analysis using high-performance liquid chromatography. It was supposed that these drugs were almost metabolized in vivo because the total excreted amounts of CPZ and CPZSO via urinary and biliary route were lower than 1.4% and 10.61% of the administered dose, respectively. And also, it was found that the fraction of systemic clearance of CPZ which formed CPZSO $(F_{mi})$ was 0.115. These results showed that CPZ was sulfoxized by 11.5% in rats and the residue would be metabolized via the other routes.

• 약학회지
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• 제55권1호
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• pp.11-15
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• 2011

Zabofloxacin is a novel broad spectrum fluoroquinolone with excellent anti-pneumococcal activity. We investigated the in vitro activity of zabofloxacin against clinical isolates of gram-positive bacteria and the in vivo activity against systemic infection in mice. Zabofloxacin was very active against gram-positive bacteria except QRSA (Quinolone-resistant S. aureus) and VRE(Vancomycin-resistant Enterococci). Especially, zabofloxacin was extremely potent against clinical isolates of Streptococci. Zabofloxacin was as active as gemifloxacin against systemic infection in mice. In view of its improved antibacterial activities against gram-positive bacteria and good pharmacokinetic profiles in animals, the clinical usefulness of zabofloxacin should be established by further studies.

• 한국임상수의학회지
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• 제14권2호
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• pp.195-200
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• 1997

In order to compare the pharmacokinetic profiles of enrofloxacin-HCL)ENFLX-HCL) and enrofloxacin-KOH (ENFLX-KOH) after oral administration in broiler chickens, the study was performed. The chickens used in this study weighed $1.82 {\pm}0.2 kg$ and clinically healthy. The dose of intravenous and lral administration was 5 mg per kg of body weight as enrofloxacin. After intravenous injection of enrofloxacin, it showed two-compartment model with the rapid distribution phase and the slow elimination phase. The mean apparent volume of distribution (Vd) was 2.70 l/kg. The mean half-life of elimination and distribution showed 8.26 h and 0.44 h, respectively. The mean area under curve (AUC) was calculated as $19.7 {\mu} g{\cdot} h/ml$. After oral administration of ENFLX-HCL and ENFLX-KOH with a rate of dose 5 mg of enrofloxacin/kg of body weight, Both of the products were showed one-compartment model unlike that of i.v. enrofloxacin standard solution showed the mean bioavailability of 79.64% for the ENFLX-KOG and 86.24% for the ENFLX-HCL. The mean total body clearance of the former was 0.24 l/kg/h and the latter 0.42 l/kg/h. Both enorfloxacin formulations seemed to have good tissue distribution and penetration as indicated by large volume of distribution : 2.72 l/kg for the -KOH and 4.44 l/kg for the -HCL. With the results obtained in this study, ENFLX-HCL could be used in place of its salt form in chickens.

• 약학회지
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• 제48권5호
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• pp.297-302
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• 2004

The purpose of the present study was to evaluate the bioequivalence of two cimetidine tablets, Tagamet (Yuhan Pharm. Co., Ltd.) and Nex (Bi-nex Pharm. Co., Ltd.), according to the guidelines of Korea Food and Drug Administration (KFDA). The cimetidine release from the two cimetidine tablets in vitro was tested using KP Apparatus I method with various dissolution media (pH 1.2, 4.0, 6.8 buffer solutions and water). The dissolution profiles of two cimetidine tablets were very similar at all dissolution media. Twenty four healthy male volunteers were divided into two groups with a randomized $2{\times}2$ cross-over study. After four tablets (800 mg cimetidine) were orally administrated, blood was taken and the concentrations of cimetidine in serum were determined using HPLC with UV detector. The pharmacokinetic parameters such as $AUC_{t}$, $C_{max}$ and $T_{max}$ were determined. The result showed that the differences in $AUC_{t}$, and $C_{max}$ between two cimetidine tablets based on the Tagamet were -6.82% and -12.98%, respectively. There were no sequence effects between two tablets in these parameters. The 90% confidence intervals using logarithmically transformed data were within the acceptance range of log(0.8) to log(1.25) (e.g., log(0.90)log(0.97) and log(0.82)log(0.93) for $AUC_{t}$ and $C_{max}$, respectively), indicating that Thrumetin tablet was bioequivalent to Tagamet tablet.

• Journal of Ginseng Research
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• 제47권2호
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• pp.283-290
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• 2023

Hypercoagulability is frequently observed in patients with severe coronavirus disease-2019 (COVID-19). Platelets are a favorable target for effectively treating hypercoagulability in COVID-19 patients as platelet hyperactivity has also been observed. It is difficult to develop a treatment for COVID-19 that will be effective against all variants and the use of antivirals may not be fully effective against COVID-19 as activated platelets have been detected in patients with COVID-19. Therefore, patients with less severe side effects often turn toward natural remedies. Numerous phytochemicals are being investigated for their potential to treat a variety of illnesses, including cancer and bacterial and viral infections. Natural products have been used to alleviate COVID-19 symptoms. Panax ginseng has potential for managing cardiovascular diseases and could be a treatment for COVID-19 by targeting the coagulation cascade and platelet activation. Using molecular docking, we analyzed the interactions of bioactive chemicals in P. ginseng with important proteins and receptors involved in platelet activation. Furthermore, the SwissADME online tool was used to calculate the pharmacokinetics and drug-likeness properties of the lead compounds of P. ginseng. Dianthramine, deoxyharrtingtonine, and suchilactone were determined to have favorable pharmacokinetic profiles.

• 대한방사성의약품학회지
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• 제6권2호
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• pp.155-164
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• 2020

Polyethylene glycol (PEG) has been the most commonly used polymer for the past few decades in the field of biomedical applications due to its gold standard stealth effect. PEGylation of antibody-drug conjugates, liposomes, peptides, nanoparticles, and proteins is done to improve their pharmaceutical efficacy and pharmacokinetic properties. PEGylation of antibodies with various PEG linkers improves targeting ability by increasing the blood circulation time and thus enhances the biodistribution profiles. It also assists in minimizing the immediate capture by the reticuloendothelial system. In this review, we summarize the effect of PEG linkers in an antibody conjugation and their pharmacokinetics in the field of biomedical imaging.

• 대한예방한의학회지
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• 제20권2호
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• pp.97-109
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• 2016

Objectives : The effects of Jaeumkanghwatang (JEKHT) co-administration on the pharmacokinetics of tamoxifen were observed after oral combination treatment of tamoxifen 50 mg/kg with JEKHT 100 mg/kg on JEKHT 6-day repeated oral pretreated rats with 8-day repeated co-administration to confirm the effects of JEKHT co-administration on the pharmacokinetics of tamoxifen. Methods : Six days after pretreatment of JEKHT 100 mg/kg, tamoxifen 50 mg/kg was co-administered with JEKHT 100 mg/kg, once a day for 8 days within 5 min. The blood were collected at 30 min before administration, 30 min, 1, 2, 3, 4, 6, 8 and 24 hrs after end of first and last 8th tamoxifen treatment, and plasma concentrations of tamoxifen were analyzed using LC-MS/MS methods. PK parameters of tamoxifen ($T_{max}$, $C_{max}$, AUC, $t_{1/2}$ and $MRT_{inf}$) were analysis as compared with tamoxifen single administered. Results : Six-day repeated oral pretreatment of JEKHT and 8-day repeated oral co-administration of tamoxifen within 5 min did not influenced on the plasma concentrations and pharmacokinetic parameters of tamoxifen, oral bioavailability, as compared with tamoxifen single treated rats, except for some negligible effects. Conclusions : It is concluded that JEKHT did not influenced on the plasma concentrations and pharmacokinetic parameters, the oral bioavailability of tamoxifen. Therefore, it is considered that co-administration of JEKHT and tamoxifen will be provide an effective novel treatment regimen on the comprehensive and integrative medicine for breast cancer patients, if they showed favorable synergic effects on the pharmacodynamics or reduce the tamoxifen treatment related toxicity and side effects in future studies.

• The Korean Journal of Physiology and Pharmacology
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• 제20권3호
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• pp.245-251
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• 2016

The objective of this study was to externally validate a new dosing scheme for busulfan. Thirty-seven adult patients who received busulfan as conditioning therapy for hematopoietic stem cell transplantation (HCT) participated in this prospective study. Patients were randomized to receive intravenous busulfan, either as the conventional dosage (3.2 mg/kg daily) or according to the new dosing scheme based on their actual body weight (ABW) ($23{\times}ABW^{0.5}mg\;daily$) targeting an area under the concentration-time curve (AUC) of $5924{\mu}M{\cdot}min$. Pharmacokinetic profiles were collected using a limited sampling strategy by randomly selecting 2 time points at 3.5, 5, 6, 7 or 22 hours after starting busulfan administration. Using an established population pharmacokinetic model with NONMEM software, busulfan concentrations at the available blood sampling times were predicted from dosage history and demographic data. The predicted and measured concentrations were compared by a visual predictive check (VPC). Maximum a posteriori Bayesian estimators were estimated to calculate the predicted AUC ($AUC_{PRED}$). The accuracy and precision of the $AUC_{PRED}$ values were assessed by calculating the mean prediction error (MPE) and root mean squared prediction error (RMSE), and compared with the target AUC of $5924{\mu}M{\cdot}min$. VPC showed that most data fell within the 95% prediction interval. MPE and RMSE of $AUC_{PRED}$ were -5.8% and 20.6%, respectively, in the conventional dosing group and -2.1% and 14.0%, respectively, in the new dosing scheme group. These findings demonstrated the validity of a new dosing scheme for daily intravenous busulfan used as conditioning therapy for HCT.