• Korean Journal of Veterinary Research
• /
• v.35 no.4
• /
• pp.815-822
• /
• 1995

The toxicokinetics of rifapentine was studied after an oral administration to beagle dogs. High-performance liquid chromatography(HPLC) using column-switching technique was performed to determine the serum concentrations of rifapentine. The pharmacokinetic profiles of rifapentine were analysed using one-compartment open model. Following a single oral administration of 10mg/kg, pharmacokinetic parameters were determined as follows: maximum serum concentration($C_{max}$), $28.90{\mu}g/ml$; maximum concentration time($T_{max}$), 3.7hr; elimination half-life($t_{1/2}$, 4.7hr; area under the curve(AUC), $339.0{\mu}g{\cdot}hr/ml$; volume of disiribution/bioavailability (Vd/F), 0.21 l/kg; lag time, 24min; absorption rate constant($k_a$), $0.445hr^{-1}$; elimination rate constant($k_{el}$), $0.148hr^{-1}$. After 6 month multiple oral doses of 10mg/kg/day, parameters were as follows: $C_{max}$, $34.40{\mu}g/ml$; $T_{max}$, 2.6hr; $t_{1/2}$, 6.7hr; AUC, $391.3{\mu}g{\cdot}hr/ml$; Vd/F, 0.291/kg; $k_a$, $0.976hr^{-1}$; $k_{el}$, $0.104hr^{-1}$. The consistant kinetic parameters after a single and multiple oral administration show that there was no accumulation of rifapentine after 6 month oral administration. We also simulated the concentration of rifapentine after oral multiple administration of 10 and 50mg/kg/ day, based on the parameters obtained form the single administration. The measured serum concentrations of rifapentine were well fitted to the simulated results. The simulated results show that rifapentine readily reaches to steady-state after about 3 doses and the steady-state serum concentrations($C_{ss}$) are fluctuated in between $2.2{\sim}25.2{\mu}g/ml$, and $10.6{\sim}125.2{\mu}g/ml$ at the doses of 10 and 50mg/kg/day, respectively.

• Journal of Pharmaceutical Investigation
• /
• v.34 no.3
• /
• pp.215-222
• /
• 2004

The purpose of the present study was designed to evaluate the bioequivalence of two oxiracetam tablets, Neuromed tablet (Korea Drug Co., reference drug) and Neuracetam tablet (Sam Jin Pharmaceutical Co., test drug), according to the guidelines of Korea Food and Drug Administration (KFDA). Release of oxiracetam from the tablet in vitro was tested using KP VIII Apparatus II method with various dissolution media (pH 1.2, 4.0, 6.8 buffer solution and water). Twenty-four healthy volunteers, $23.7\;{\pm}\;2.4$ year in age and $68.9\;{\pm}\;6.2$ kg in body weight, were divided into two groups and a randomized $2{\times}2$ cross-over study was performed. After oral administration of a tablet containing 800 mg of oxiracetam, blood samples were taken at predetermined time intervals and concentrations of oxiracetam in plasma were determined using HPLC-MS-MS. The dissolution profiles of two formulations were very similar at all dissolution media. In addition, pharmacokinetic parameters such as $AUC_t$, $C_{max}$ and $T_{max}$ were calculated and ANOVA test was utilized for the statistical analysis of the parameters using logarithmically transformed $AUC_t$ and $C_{max}$ untransformed $T_{max}$. The results showed that the differences between two formulations based on the reference drug were 0.42%, 0.45% and -12.58% for $AUC_t$, $C_{max}$ and $T_{max}$, respectively. There were no sequence effects between two formulations in these parameters. The 90% confidence intervals for the log transformed data were within the acceptance range of log 0.8 to log 1.25 (e.g., $log0.94{\sim}log1.06$ and $log0.90{\sim}log1.07$ for $AUC_t$, and $C_{max}$, respectively), indicating that Neuracetam tablet is bioequivalent to Neuromed tablet. The major pharmacokinetic parameters, $AUC_t$, and $C_{max}$ met the criteria set by KFDA for bioequivalence indicating that Neuracetam tablet is bioequivalent to Neuromed tablet.

• Translational and Clinical Pharmacology
• /
• v.25 no.3
• /
• pp.153-156
• /
• 2017

UI14SDF100CW is a chewable tablet of sildenafil citrate, which was developed to improve compliance through convenience of administration. The purpose of this study was to compare the pharmacokinetic (PK) properties of sildenafil citrate chewable tablets (UI14SDF100CW) and conventional sildenafil citrate film-coated tablets ($Viagra^{(R)}$, Pfizer). A randomized, open-label, single dose, two-treatment, two-period, two-way crossover study was conducted in 60 healthy male volunteers. In each period, the subjects received a single oral dose of UI14SDF100CW or $Viagra^{(R)}$ (both tablets contain 140.45 mg of sildenafil citrate, which is equivalent to 100 mg of sildenafil). Serial blood samples were collected up to 24 h post-dose for PK analysis. The plasma concentration of sildenafil was determined using a validated HPLC-MS/MS assay. PK parameters of sildenafil were calculated using non-compartmental methods. The plasma concentration-time profiles of sildenafil in both formulations were similar. For UI14SDF100CW, the $C_{max}$ and $AUC_{last}$ of sildenafil were $1068.69{\pm}458.25$ (mean${\pm}$standard deviation) mg/L and $3580.59{\pm}1680.29h{\cdot}mg/L$, and the corresponding values for $Viagra^{(R)}$ were $1146.84{\pm}501.70mg/L$ and $3406.35{\pm}1452.31h{\cdot}mg/L$, respectively. The geometric mean ratios (90% confidence intervals) of UI14SDF100CW to $Viagra^{(R)}$ for $C_{max}$ and $AUC_{last}$ were 0.933 (0.853-1.021) and 1.034 (0.969-1.108), respectively, which met the bioequivalence criteria of Korean regulatory agency. In conclusion, UI14SDF100CW and $Viagra^{(R)}$ showed similar PK properties. Therefore, UI14SDF100CW can be an alternative to sildenafil for the treatment of erectile dysfunction, providing better compliance.

• KOREAN JOURNAL OF CROP SCIENCE
• /
• v.67 no.4
• /
• pp.305-318
• /
• 2022

To minimize the effects of aging-related comorbidities and to maintain a good quality of life and physical independence for a longer period, the improvement of lifestyle and dietary habits is essential, and healthy foods can be helpful. Among them, medicinal plant such as ginseng (Panax ginseng) and bellflower (Platycodon grandiflorum) contain natural functional substances and have been used for disease treatment and prevention since ancient times. This review summarizes the scientific of these treatments basis by investigating the pharmacological and pharmacokinetic effects of major functional substances on the aging-related health effects of Panax ginseng and Platycodon grandiflorum. The main functional substances of Panax ginseng and Platycodon grandiflorum are saponins, which have a similar molecular structure and confirmed anti-inflammatory, antioxidant, neuroprotective, anticancer, and anti-metabolic syndrome effects (improvement of hypertension, dyslipidemia, diabetes, and obesity). Both types of saponins in Panax ginseng (Ginseonside) and Platycodon grandiflorum (Platycoside) have very low absorption profiles in their purified state, but methods to increase absorption in the body through extraction or fermentation have been studied.

• Analytical Science and Technology
• /
• v.22 no.1
• /
• pp.101-108
• /
• 2009

The bioequivalence of two pioglitazone tablets, Actos$^{(R)}$ tablet (Takeda Chemical Industries, reference drug) and Pioglitazone tablet (Boryung Company, test drug) was evaluated according to the guidelines of Korea Food and Drug Administration. Twenty-eight healthy male Korean volunteers received each medicine (pioglitazone dose of 30 mg) in a $2{\times}2$ crossover study with one week washout interval. After drug administration, blood samples were collected at specific time intervals from 0-36 hours. The plasma concentrations of pioglitazone were determined by high performance liquid chromatography-tandem mass spectrometry (LC-MS/MS). The total chromatographic run time was 5 min and calibration curves were linear over the concentration range of 5-2000 ng/mL for pioglitazone. The method was validated for selectivity, sensitivity, linearity, accuracy and precision. The pharmacokinetic parameters were determined from the plasma concentration-time profiles of both formulations. The primary calculated pharmacokinetic parameters were compared statistically to evaluate bioequivalence between the two preparations. The 90% confidence intervals of the $AUC_t$ ratio and the $C_{max}$ ratio for Pioglitazone tablet and Actos$^{(R)}$ tablet were log0.9422~log1.1040 and log0.9200~log1.1556, respectively. Based on the statistical considerations, we can conclude that the test drug, Pioglitazone tablet was bioequivalent to the reference drug, Actos$^{(R)}$ tablet.

• Journal of Pharmaceutical Investigation
• /
• v.39 no.3
• /
• pp.221-226
• /
• 2009

The purpose of the present study was to evaluate the bioequivalence of two alprazolam tablets, Xanax 0.25 mg (Pharmacia Korea Pharm. Co., Ltd.) and Zyren 0.25 mg (Kwang Dong Pharm. Co., Ltd.), according to the guidelines of Korea Food and Drug Administration (KFDA). The alprazolam release from two alprazolam tablets in vitro was tested using KP VIII Apparatus II method with various dissolution media (pH 1.2, 4.0, 6.8 buffer solutions and water). The dissolution profiles of two alprazolam 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 (1 mg alprazolam) were orally administrated, blood was taken and the concentrations of alprazolam in serum were determined using LC/MS/MS. The pharmacokinetic parameters such as $AUC_t$, $C_max$ and $T_max$were determined. Our results showed that the differences in $AUC_t$, $C_max$ and $T_max$ between two alprazolam tablets based on the Xanax were -11.65%, -4.44% and -39.31%, respectively. There were no sequence effects between two tablets in these parameter. The 90% confidence intervals using logarithmically transformed data were within the acceptance range of log(0.8) to log(1.25)(e.g., log(0.8386)${\sim}$log(0.9453) and log(0.8596)${\sim}$log(1.1040) for $AUC_t$, $C_max$, respectively). Thus, Zyren 0.25 mg tablet was bioequivalent to Xanax 0.25 mg tablet.

• Journal of Physiology & Pathology in Korean Medicine
• /
• v.21 no.1
• /
• pp.104-110
• /
• 2007

Aralia contientalis show several beneficial effects including anti-oxidant effects. Aralia contientalis is used as a therapeutic agent to stop haemorrhages and a tonic to promoted health in Korean and Chinese medicine. The pharmacokinetic profiles of the main Aralia contientalis is still not accurately investigated. In present study, I examined the effects of water extracts of Aralia contientalis on high cholesterol diet atherosclerosis-induced rats in serum and abdominal aorta. A total of 3-week old 9 male rats of Sprague-Dawley were divided into 3 groups and fed with the basal diet (normal group), high cholesterol diet (atherosclerosis induced group) for 8 weeks, high cholesterol diet supplemented with water extracts of Aralia contientalis (Aralia contientalis group) for 2 weeks. And rats were sacrificed, serum lipid level, abodominal aortic anti-oxidant activities and lipid peroxide were measured. These results indicated that serum total cholesterl, LDL-cholesterol, triglycerides concentration significently lowered in Aralia contientalis group than high cholesterol diet group. But HDL-cholesterol concentraion significently higher in Aralia contientalis group than high cholesterol diet group.

• The Korean Journal of Physiology and Pharmacology
• /
• v.19 no.2
• /
• pp.99-104
• /
• 2015

The aim of this study is to develop a physiologically based pharmacokinetic (PBPK) model in intra-abdominal infected rats, and extrapolate it to human to predict moxifloxacin pharmacokinetics profiles in various tissues in intra-abdominal infected human. 12 male rats with intra- abdominal infections, induced by Escherichia coli, received a single dose of 40 mg/kg body weight of moxifloxacin. Blood plasma was collected at 5, 10, 20, 30, 60, 120, 240, 480, 1440 min after drug injection. A PBPK model was developed in rats and extrapolated to human using GastroPlus software. The predictions were assessed by comparing predictions and observations. In the plasma concentration versus time profile of moxifloxcinin rats, $C_{max}$ was $11.151{\mu}g/mL$ at 5 min after the intravenous injection and $t_{1/2}$ was 2.936 h. Plasma concentration and kinetics in human were predicted and compared with observed datas. Moxifloxacin penetrated and accumulated with high concentrations in redmarrow, lung, skin, heart, liver, kidney, spleen, muscle tissues in human with intra-abdominal infection. The predicted tissue to plasma concentration ratios in abdominal viscera were between 1.1 and 2.2. When rat plasma concentrations were known, extrapolation of a PBPK model was a method to predict drug pharmacokinetics and penetration in human. Moxifloxacin has a good penetration into liver, kidney, spleen, as well as other tissues in intra-abdominal infected human. Close monitoring are necessary when using moxifloxacin due to its high concentration distribution. This pathological model extrapolation may provide reference to the PK/PD study of antibacterial agents.

• Biomolecules & Therapeutics
• /
• v.5 no.2
• /
• pp.187-193
• /
• 1997

The in vivo and in vivo antibacterial activity of DW-116, a newly synthesized fluoroquinolone, were compared with those of other quinolones. DW-116 exhibited more potent antibacterial activity than rufloxacin and lower activity than ofloxacin and ciprofloxacin in in vivo assay But, DW-116 particularly showed strong activity against the family of staphylococci including methicillin-sensitive staphylococcus and its activity was more active than that of ciprofloxacin. The time-kill curve studies showed rapid bactericidal activity for DW-116. The post-antibiotic effect of DW-116 was observed between 0.66 and 5 hours. The therapeutic efficacy of DW-116 against respiratory infection with P. aeruginosa was as strong as that of ciprofloxacin and its effect against urinary tract in(traction with E. coli was more effective than rufloxacin. The excellent therapeutic efficacy of DW-116 against these local infections is due to its good pharmacokinetic profiles.

• Journal of Pharmaceutical Investigation
• /
• v.25 no.1
• /
• pp.19-29
• /
• 1995

The study was carried out to develop useful formulation for omeprazole(OMP) through OMP-ethylendiamine complex(OMPED), and the pharmaceutical properties of formula were tested to find out the difference in vivo behaviors of formulations between the free and complexed OMP. Oral and suppository dosage forms were also formulated and the dissolution profiles and pharmacokinetic parameters were measured to observe the difference in bioavailability between the free and complex form, and the correlation between dissolution rate and bioavailability was evaluated. The results are summarized as follows; In the case of formulation for oral administration, the release of OMP from enteric OMPED pellets was found satisfactory to the requirement standard and no decomposition of OMP in the pellets was found in acidic solution. Therefore the enteric OMPED pellets are anticipated to be a stable formulation. The release of OMP from OMPED tablet with chitosan as excipient and coated with cellulose acetate phthalate was found to be significantly retarded. The results of bioavailability test for OMP and OMPED tablets with lactose-excipient showed that the AUC value of OMP tablet was $116.89\;{\mu}g\;{\cdot}\;min/ml$, that of OMPED tablet was $161.10\;{\mu}g\;{\cdot}\;min/ml$, respectively. The reason why was thought that OMP decomposes more readily in body than OMPED, and the AUC of the tablet with chitosan-excipient and coated with cellulose acetate phthalate was most enhanced. In the case of bioavailability for suppositories with OMP, $OMP-{\beta}\;-cyclodextrin$ complex and OMPED, the AUC of OMPED suppository was most increased. From the above results, it is thought that the more stable and bioavailable oral or rectal dosage forms could be developed by using the OMPED as a potential OMP complex.