• 대한핵의학회:학술대회논문집
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• 대한핵의학회 2001년도 제40차 춘계학술대회 및 연수교육
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• pp.51-55
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• 2001

Regional MBF and MRGlc can be accurately estimated with N-13 ammonia and FDG PET using tracer kinetic methods including compartmental and non-compartmental approaches. Compartment modeling approaches are physiologically well characterized, but are methodologically more complicated. Noncompartmental analysis are easier to implement while the limitations and assumptions of the methods should be understood prior to the application of the method.

• 한국임상약학회지
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• 제16권1호
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• pp.63-68
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• 2006

Gabapentin, 1-(aminomethyl-1-cyclohexyl)acetic acid, is anew antiepileptic drug related to ${\gamma}-aminobutyric$ acid(GABA) currently being introduced in therapy worldwide. The bioavailability and pharmacokinetics of gabapentin capsules were examined in 22 volunteers who received a single oral dose in the fasting state by randomized balanced $2{\times}2$ crossover design. After dosing, blood samples were collected for a period of 24 hours and analyzed by liquid chromatography-tandem mass spectrometry (LC/MS/MS). Time course of plasma gabapentin concentration was analyzed with non-compartmental and compartmental approaches. $WinNonlin^{(R)}$, the kinetic computer program, was used for compartmental analysis. One compartment model with first-order input, first-order output with no lag time and weighting by $1/(predieted\;y)^2$ was chosen as the most appropriate pharmacokinetic model for the volunteers. The major pharmacokinetic parameters $(AUC_{0-24hr},\;AUC_{inf},\;C_{max}\;and\;T_{max})$ and other parameters $(K_a,\;K_{el},\;V_d/F\;and\;Cl/F)$ of $Gapentin^{TM}$ (test drug) and $Neurontin^{TM}$ (reference drug) were estimated by non-compartmental analysis and compartmental analysis. The 90% confidence intervals of mean difference of logarithmic transformed $AUC_{0-24hr}\;and\;C_{max}$ were $log(0.9106){\sim}log(1.l254)\;and\;log(0.8521){\sim}log(1.0505)$, respectively. It shows that the bioavailability of the test drug is equivalent with that of the reference drug. There was no statistically significant difference between the two drugs in all pharmacokinetic parameters.

• Journal of Pharmaceutical Investigation
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• 제36권2호
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• pp.123-129
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• 2006

A method determining the plasma concentration of clotiazepam was developed by using gas chromatography/mass spectrometry with an ion-trap detector and was validated for applying pharmacokinetics to human volunteers orally taken 5 mg dose of clotiazepam. The detection limit was 1 ng/ml and the limit of quantitation was 5 ng/mt. Intraday reproducibility and accuracy bias % were less than 8.2 and 10.2% with inter-day variations for those being within 7.0 and 13.8%, respectively. The recovery of clotiazepam was higher than 87%. The principal pharmacokinetic parameters were determined from the plasma concentration-time plot by non-compartmental or two-compartmental analysis. In non-compartmental analysis, the elimination half-life of 10.4 hr and the area under the curve of 651.3 ng hr/ml were determined, and the maximal concentration (158.6 ng/ml) in the plasma was obtained at 0.56 hr post-dose. The developed method can be appropriate to apply pharmacokinetics and bioequivalence of clotiazepam.

• Biomolecules & Therapeutics
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• 제25권6호
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• pp.648-658
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• 2017

7-O-Succinyl macrolactin A (SMA) exerts several pharmacological effects including anti-bacterial, anti-inflammation, and anti-cancer activities. Recently, SMA has been extensively evaluated as an anti-cancer drug. Thus, the objectives of the present study were to characterise the pharmacokinetics of SMA via both non-compartmental and compartmental analysis in mice, rats, and dogs, and to derive an appropriate first-in-man dose based on allometric scaling of the animal data. The time courses of plasma SMA concentrations after intravenous administration to rats and dogs were analysed retrospectively, as were data collected after intraperitoneal SMA injection in mice. Pharmacokinetic parameters were estimated via both noncompartmental and compartmental analysis, and were correlated with body weight and/or the potential maximum life-span. The clearance and distribution volume of SMA in humans were predicted, and a first-in-man dose proposed. A two-compartment model best described the time courses of SMA plasma concentrations after a saturation elimination process was applied to fit the dataset obtained from rats. Incorporation of the maximum potential life-span during allometric scaling was required to improve the estimation of human clearance. The SMA clearance and the distribution volume in the steady state, in a 70-kg adult male, were estimated to be 30.6 L/h and 19.5 L, respectively. To meet the area under the curve (AUC) required for anti-tumour activity, a dose of 100 mg (~1.5 mg/kg) was finally proposed as the first dose for a 70-kg human. Although toxicological profiles derived from non-clinical studies must be considered before any final decision is made, our work will facilitate clinical studies on SMA.

• The Korean Journal of Physiology and Pharmacology
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• 제25권6호
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• pp.545-553
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• 2021

Fixed-dose combinations development requires pharmacokinetic drugdrug interaction (DDI) studies between active ingredients. For some drugs, pharmacokinetic properties such as long half-life or delayed distribution, make it difficult to conduct such clinical trials and to estimate the exact magnitude of DDI. In this study, the conventional (non-compartmental analysis and bioequivalence [BE]) and model-based analyses were compared for their performance to evaluate DDI using amlodipine as an example. Raw data without DDI or simulated data using pharmacokinetic models were compared to the data obtained after concomitant administration. Regardless of the methodology, all the results fell within the classical BE limit. It was shown that the model-based approach may be valid as the conventional approach and reduce the possibility of DDI overestimation. Several advantages (i.e., quantitative changes in parameters and precision of confidence interval) of the model-based approach were demonstrated, and possible application methods were proposed. Therefore, it is expected that the model-based analysis is appropriately utilized according to the situation and purpose.

• 한국임상수의학회지
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• 제24권3호
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• pp.308-311
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• 2007

본 연구는 육계에 톨투라주릴을 체중당 10 mg 및 40 mg 용량으로 경구 투여한 후 톨투라주릴의 약물동태학적 분석을 실시하였다. 혈장내의 톨투라주릴의 정량은 액체크로마토그래프/질량분석기를 사용하였으며, 경구 투여후 혈장 농도-시간 자료는 non-compartmental analysis를 이용하여 분석하였다. 톨투라주릴을 10 mg/kg 및 40 mg/kg 용량으로 각각 경구투여 후 혈중최고농도($18.04{\pm}5.50{\mu}g/mL$ 및 $47.15{\pm}9.40{\mu}g/mL$)는 $4.33{\pm}1.51h$ 및 $3.67{\pm}1.51h$에 나타났다. 소실반감기는 $11.40{\pm}4.68h$ 및 $11.64{\pm}4.08h$으로 각각 나타났다. 톨투라주릴의 경구투여 후 혈중최고농도 및 곡선하면적은 용량이 증가함에 따라 증가하였다.

• 대한수의학회지
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• 제53권2호
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• pp.77-82
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• 2013

The present study was planned to evaluate the bioequivalence of two commercial formulations of enrofloxacin, which have been marketed as 10% injectable solution after intramuscular administration at a single dose of 2.5 mg/kg body weight to 12 clinically healthy goats The study was carried out on the basis of crossover design. The two formulations were: Baytril as a reference product and Spectrama Vet as a test product. The plasma concentrations of enrofloxacin were measured by high performance liquid chromatography (HPLC) with UV detector. The pharmacokinetics of that data was performed using non-compartmental analysis. The maximum plasma concentration ($C_{max}$), time to reach peak concentration ($T_{max}$), area under concentration-time curve (AUC), elimination half-life ($t_{0.5el}$) were 1.14 and $1.05{\mu}g/mL$, 0.79 and 0.83 h, 5.70 and $5.79{\mu}g.h/mL$, 5.19 and 5.39 h for Baytril and Spectrama Vet, respectively. The 90% confidence interval for the mean ratio of $T_{max}$, $C_{max}$ and AUC were 94.72-116.2, 87.88-97.16 and 86.44-118.72%, respectively. These values falls within the European Medicines Agency bioequivalence acceptance range of 80-125% for both $T_{max}$ and AUC and between 75-133% for $C_{max}$. In conclusion, Spectrama-Vet is bioequivalent to Baytril and both products can be used as interchangeable drug in veterinary medicine practice.

• Journal of Veterinary Science
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• 제21권3호
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• pp.35.1-35.11
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• 2020

Background: Despite common use of tylosin in turkeys, the pharmacokinetic (PK) data for this drug in turkeys is limited. Within a few months of growth, PK of drugs in turkeys undergoes changes that may decrease their efficacy due to variable internal exposure. Objectives: The objective of this study was to investigate the influence of age on the PK of a single intravenous (i.v.) and oral administration of tylosin to turkeys at a dose of 10 and 50 mg/kg, respectively. Methods: Plasma drug concentrations were measured using high-performance liquid chromatography with UV detection. The PK parameters were assessed by means of non-compartmental approach and were subjected to allometric analysis. Results: During a 2.5-month-long period of growth from 1.4 to 14.7 kg, the median value for area under the concentration-time curve after i.v. administration increased from 2.61 to 7.15 mg × h/L and the body clearance decreased from a median of 3.81 to 1.42 L/h/kg. Over the same time, the median elimination half-life increased from 1.03 to 2.96 h. For the oral administration a similar trend was noted but the differences were less pronounced. Bioavailability was variable (5.76%-21.59%) and age-independent. For both routes, the plasma concentration of the major tylosin metabolite, tylosin D, was minimal. Protein binding was age-independent and did not exceed 50%. Allometric analysis indicated a relatively poor predictivity of clearance, volume of distribution and elimination half-life for tylosin in turkeys. Conclusions: Age has a significant impact on tylosin PK in turkeys and dosage adjustment may be needed, particularly in young individuals.

• The Korean Journal of Physiology and Pharmacology
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• 제16권4호
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• pp.249-253
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• 2012

We analyzed the pharmacokinetics of C3G on data from twelve subjects, after 2-week multiple dosing of black bean (Phaseolus vulgaris, Cheongjakong-3-ho) seed coat extract, using the mixed effect analysis method (NONMEM, Ver. 6.2), as well as the conventional non-compartmental method. We also examined the safety and tolerability. The PK analysis used plasma concentrations of the C3G on day 1 and 14. There was no observed accumulation of C3G after 2-week multiple dosing of black bean seed coat extract. The typical point estimates of PK were CL (clearance)=3,420 l/h, V (volume)=7,280 L, Ka (absorption constant)=9.94 $h^{-1}$, ALAG (lag time)=0.217 h. The black bean seed coat extract was well tolerated and there were no serious adverse events. In this study, we confirmed that a significant amount of C3G was absorbed in human after given the black bean seed coat extract.

• 한국임상약학회지
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• 제13권1호
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• pp.13-17
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• 2003

This study was carried out to compare the bioavailability of $Ceclex^{(R)}$ SR TAB (test drug, cefaclor 375 mg/Tablet) with that of Ceclor $MR^{(R)}$ SR IAB (reference drug) and to estimate the pharmacokinetic parameters of cefaclor in healthy Korean volunteers. The bioavailability was examined on 24 healthy volunteers who received a single dose (375 mg) of each drug in the fasting state in a randomized balanced 2-way crossover design. After dosing, blood samples were collected for a period of 7 hours. Plasma concentrations of cefaclor were determined using HPLC with UV detection. The pharmacokinetic parameters $(AUC_{0-7h},\;C_{max},\;T_{max},\;AUC_{inf},\;K_e,\;t_{1/2},\;V_d/F,\;and\;CL/F)$ were calculated with non-compartmental pharmacokinetic analysis. The ANOVA test was utilized for the statistical analysis of the $T_{max}$, log-transformed $AUC_{0-7h$}$, log-transformed $C_{max},\;t_{1/2},\;V_d/F$, and $CL/F$. The ratios of geometric means of $AUC_{0-7h}\;and\;C_{max}$ between test drug End reference drug were $95.67\%\;(8.55\;vs\;8.18{\mu}g{\cdot}hr/ml)\;and\;103.86\%\;(2.85\;vs\;2.96{\mu}g/ml)$, respectively. The $T_{max}$ of test drug and reference drug was $2.56\pm0.15\;and\;2.23\pm0.13\;hrs,\;respectively.\;The\;90\%$ confidence intervals of mean difference of logarithmic transformed $AUC_{0-7h}\;and\;C_{max}$ were log0.90-log1.04 and log0.91-log1.13, respectively. It shows that the bioavailability of test drug is equivalent with that of reference drug.