• 한국임상약학회지
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• 제17권1호
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• pp.1-5
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• 2007

A computerized chemotherapy order system (CCOS) was developed to improve the accuracy and efficiency of prescriptions for pharmacy medication scheduling at a teaching hospital, Asan Medical Center, Seoul, Korea. We evaluated the system by comparing prescriptions before and after the implementation of the system and by analyzing the effects of the system on dosing accuracy (only against 5-FU), prescription change, overdoses above maximum limit and medication disposal in non computerized program group (control group) and CCOS group. In terms of dosing accuracy, prescription error rate (%) was significantly decreased in CCOS groups compared with the control group. The rate of prescription changes was also significantly decreased in CCOS groups. Regarding overdoses above maximum limit, we found that there was no prescription order exceeding the dosage limit in CCOS groups in contrast to significant overdoses in control group. In terms of medication disposal, there was no significant difference between 2 groups. We suggest that the computerized chemotherapy order system for chemotherapy may bean important and useful tool for minimizing prescribing errors in the hospitals.

• 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.

• 한국환경보건학회지
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• 제40권5호
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• pp.407-412
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• 2014

Objectives: The internal dose of ethyl parabens is important in order to evaluate the risk of this chemical. However, there are little PK model data for parabens to apply this. This experiment attempted PK modeling to ascertain PK values. Methods: Twenty mg/kg ethyl paraben was administered orally to Sprague-Dawley rats at the same point in time. The rats were sacrificed at times 0, 15, 30 and minutes, and 1, 2, 4, 8, 12, 24 hours after oral gavage. Blood and urine were collected and pretreated for analysis. Accuracy, precision and LOD (limit of detection) were calculated for this analysis. Ethyl paraben, detected by HPLC-MS, was applied to PK modeling using Berkeley Madonna. Results: This study showed 100.1-103.7% accuracy, 1.4-3.7% precision and a 1.0 ng/mL limit of detection. Orally administered ethyl paraben reached maximum concentration after 30 minutes of dosing in serum and urine of rats. The concentrations were 2,354 ng/mL in serum and 386,000 ng/mL in urine samples. These peak concentrations were excreted after one hour of intubation over 12 hours. For the pharmacokinetic parameters of ethyl paraben revealed using Berkeley Madonna, the absorption rate was 5.539/hour, the excretion rate was 0.048/hour, the half-life was 14.441 hours and AUC was 481,186 ng hour/mL. Conclusion: Orally administered ethyl paraben was absorbed rapidly in rats and excreted in urine. This chemical, ethyl paraben, accumulated in the body but was excreted over 12 hours after dosing.

• 약학회지
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• 제58권1호
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• pp.40-46
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• 2014

Drugs with a narrow therapeutic index (NTI) require very precise dosing. Warfarin and digoxin are the examples of NTI-drugs and dosing of them varies widely for different patients. However, in South Korea, only two strengths of warfarin and one of digoxin are commercially available. This is a big barrier for the precise dispensing and has potential safety risks to patients, particularly to elderly patients. To find a potential solution to the problem, an analysis of the prescribed doses and dispensing patterns of those drugs was performed. Data were collected by computer-facilitated prescription review in a university hospital. The period screened was from May 1st, 2012 to April 30th, 2013. All the prescriptions with either warfarin or digoxin tablets were selected for this study and dispensing patterns were analyzed according to the prescribed doses. A total of 17,017 warfarin prescriptions were analyzed; 8,148 for inpatient prescriptions, 8,869 for outpatient prescriptions, respectively. Of the 23 kinds of prescribed doses, 2 mg (19.9%) was most frequent, followed by 3 mg (13.2%) and 2.5 mg (11.7%). By analyzing the dispensing patterns, 60.3% (10,253) of the prescriptions required pill splitting and 72.0% of them were for the patients 65 years old and over. On the other hand, 4,350 digoxin prescriptions were included in this study. Of the 6 kinds of prescribed doses, 0.125 mg (71.2%) was most frequent, followed by 0.0625 mg (20.2%). Among the prescriptions for digoxin, 92.0% (3,998) should be split and 65.7% of them were for the patients aged 65 years and over. Despite limitations of strengths, various doses of warfarin and digoxin were prescribed. Furthermore, more than half of the prescriptions that required pill splitting were for elderly patients. The results from this study suggest that different strengths of warfarin and digoxin should be provided for accuracy of dispensing and safety for patients receiving them.

• Journal of Pharmaceutical Investigation
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• 제30권3호
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• pp.191-199
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• 2000

Genomics is providing targets faster than we can validate them and combinatorial chemistry is providing new chemical entities faster than we can screen them. Historically, the drug discovery cascade has been established as a sequential process initiated with a potency screening against a selected biological target. In this sequential process, pharmacokinetics was often regarded as a low-throughput activity. Typically, limited pharmacokinetics studies would be conducted prior to acceptance of a compound for safety evaluation and, as a result, compounds often failed to reach a clinical testing due to unfavorable pharmacokinetic characteristics. A new paradigm in drug discovery has emerged in which the entire sample collection is rapidly screened using robotized high-throughput assays at the outset of the program. Higher-throughput pharmacokinetics (HTPK) is being achieved through introduction of new techniques, including automation for sample preparation and new experimental approaches. A number of in vitro and in vivo methods are being developed for the HTPK. In vitro studies, in which many cell lines are used to screen absorption and metabolism, are generally faster than in vivo screening, and, in this sense, in vitro screening is often considered as a real HTPK. Despite the elegance of the in vitro models, however, in vivo screenings are always essential for the final confirmation. Among these in vivo methods, cassette dosing technique, is believed the methods that is applicable in the screening of pharmacokinetics of many compounds at a time. The widespread use of liquid chromatography (LC) interfaced to mass spectrometry (MS) or tandem mass spectrometry (MS/MS) allowed the feasibility of the cassette dosing technique. Another approach to increase the throughput of in vivo screening of pharmacokinetics is to reduce the number of sample analysis. Two common approaches are used for this purpose. First, samples from identical study designs but that contain different drug candidate can be pooled to produce single set of samples, thus, reducing sample to be analyzed. Second, for a single test compound, serial plasma samples can be pooled to produce a single composite sample for analysis. In this review, we validated the issue whether the second method can be applied to practical screening of in vivo pharmacokinetics using data from seven of our previous bioequivalence studies. For a given drug, equally spaced serial plasma samples were pooled to achieve a 'Pooled Concentration' for the drug. An area under the plasma drug concentration-time curve (AUC) was then calculated theoretically using the pooled concentration and the predicted AUC value was statistically compared with the traditionally calculated AUC value. The comparison revealed that the sample pooling method generated reasonably accurate AUC values when compared with those obtained by the traditional approach. It is especially noteworthy that the accuracy was obtained by the analysis of only one sample instead of analyses of a number of samples that necessitates a significant man-power and time. Thus, we propose the sample pooling method as an alternative to in vivo pharmacokinetic approach in the selection potential lead(s) from combinatorial libraries.

• 한국근적외분광분석학회:학술대회논문집
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• 한국근적외분광분석학회 2001년도 NIR-2001
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• pp.4101-4101
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• 2001

Information of body composition (fat and protein) in living animal is important to determine the nutrients requirement. Deuterium oxide (D2O) dilution techniques, as one of isotope dilution techniques have been useful for the prediction of body composition. However, the determination of D2O concentration is time consuming and complicated. Therefore this study was conducted to develop a new method to predict D2O concentration in plasma using near infrared spectroscopy technique (NIRS). Four dairy cows in early lactation were used. They were fed total mixed ration containing conr silage, timothy hay, and concentrates to make 17.0%CP and 14.0 MJDE/kgDM. Dosing D2O was at week 1,3 and 5 after parturition. After dosing D2O, the blood was collected from hour 0 to 72. Blood samples were then centrifuge at 3,000 rpm for 10 minutes to obtain plasma. D2O concentration was analyzed by gas chromatograph (deuterium oxide analyzable system, HK102, Shokotsusyou) after extracted from plasma by liophilization. Plasma sample was scanned by NIRS using Pacific Scientific (Neotec) model 6500 (Perstorp Analytical, Silver Spring, MD) in the range of wavelength from 1100 to 2500 nm. Calibration equation was developed using multiple linear regression. Sample from one animal (cow #550; n: 74) was used for developing the calibration while the rest three animals were used for validating the equation. The range, R and SEC of the calibration set samples were 135-925 ppm, 0.93 and 48.1 ppm, respectively. Validation of the calibration equation for three individual cows was done and the average of NIR predicted value of D2O at each collection time from three weeks injection showed a high correlation. The range, r and 53 of plasma from cow #474 were 322-840 ppm,0.93 and 53.1; cow #478 were 146-951 ppm,0.95 and 39.8; cow #942 were 313-885 ppm,0.95 and 37.2, respectively. Judgement of accuracy based on ratio of standard deviation and standard error in validation set samples (RPD) for cow #474, #478 and #942 were 2.2,4.3 and 3.4, respectively. The error in application due to the variation between individual was considered smaller than the bias from collection period, however, this prediction can be overcome with correction of standard zero-minute concentration of blood. The results of this preliminary study on the use of NIRS for determination of D2O in plasma showed very promising as shown by a convenient and satisfy accuracy. Further study on various physiological stage of animal should be done.

• 한국전자통신학회논문지
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• 제8권7호
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• pp.1033-1038
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• 2013

석유화학 단지에서는 보다 완성도 높은 제품을 위한 많은 연구 개발이 진행되고 있으며 이 과정에서 제품의 중간 및 완성 제품에 대한 분석은 필수적이다. 그러나 이와 같은 분석 작업들이 아직도 많은 부분에서 수작업에 의한 분석 시료가 제조되고 있고 위험한 화학물질에 노출되어 열악한 환경에서 분석이 이루어지고 있다. 본 연구에서는 이와 같은 문제점을 해결하기 위하여 분석 자동화를 위한 멀티 제어 시스템을 개발하였다. 또한 이들 장치의 유기적인 동작과 자동화를 위한 프로그램을 개발하여 적용하고 이들 장치의 신뢰성 검증을 위한 실험을 통하여 표준 용액 조제를 위한 정량 펌프의 정확도가 ${\pm}0.01m{\ell}$의 오차 범위를 갖는 매우 우수한 결과를 얻을 수 있었다.

• 한국임상약학회지
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• 제18권2호
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• pp.106-113
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• 2008

The aim of this study was to evaluate the bioequivalence of two domperidone preparations. Bioequivalence assessment was conducted on 34 healthy volunteers who received two tablets (Domperidone Maleate, 12.72 mg/tablet) in the fasting state, in a randomized balanced $2{\times}2$ cross-over study design. This whole study was performed according to the implementation guidelines of the Korea Food Drug Administration. After dosing of two tablets, blood samples were collected serially for a period of 36 hours. Plasma was analyzed for domperidone by using LC/MS/MS assay method. The analysis system was validated in specificity, accuracy, precision, and linearity. $AUC_t$, (the area under the plasma concentration-time curve from the zero-time to 36 hr) was calculated through the trapezoidal rule. $C_{max}$ (maximum plasma drug concentration) and $T_{max}$ (time to reach $C_{max}$) were compiled from the plasma domperidone concentration-time data of each volunteer. No significant sequence effect was found for the bioavailability parameters indicating that the cross-over design was properly performed. The 90%-Confidence intervals of the $AUC_t$ ratio and the $C_{max}$ were from log 0.8007 to log 1.1240 and log 0.8645- log 1.2483, respectively. These values were within the acceptable bioequivalence intervals between 0.80 and 1.25. Therefore, this study demonstrated that two formulations have bioequivalence with respect to the rate and extent of absorption.

• Mass Spectrometry Letters
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• 제8권4호
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• pp.98-104
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• 2017

Ginseng (Panax ginseng Meyer) is a well-known health functional food used as a traditional herbal drug in Asian countries owing to its diverse pharmacological effects. Herb-drug interactions may cause unexpected side effects of co-administered drugs by the alteration of pharmacokinetics through effects on cytochrome P450 activity. In this study, we investigated the herb-drug interactions between Korean red ginseng extract (KRG) and five CYP-specific probes in mice. The pharmacokinetics of KRG extract induced-drug interactions were studied by cassette dosing of five CYP substrates for CYP1A, 2B, 2C, 2D, and 3A and the LC-MS/MS analysis of the blood concentration of metabolites of each of the five probes. The linearity, precision, and accuracy of the quantification method of the five metabolites were successfully confirmed. The plasma concentrations of five metabolites after co-administration of different doses of the KRG extract (0, 0.5, 1, and 2 g/kg) were quantified by LC-MS/MS and dose-dependent pharmacokinetic parameters were determined. The pharmacokinetic parameters of the five metabolites were not significantly altered by the dose of the KRG extract. In conclusion, the single co-administration of KRG extract up to 2 g/kg in vivo did not cause any significant herb-drug interactions linked to the modulation of CYP activity.

• 한국임상약학회지
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• 제19권1호
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• pp.23-31
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• 2009

The aim of this study was to evaluate the pharmacokinetic parameters of two risedronate preparations. The clinical assessment was conducted on 46 healthy volunteers who received one tablet (Risedronate sodium 35 mg/tablet) in the fasting state, in a randomized balanced $2{\times}2$ cross-over study design. After dosing of one tablet containing 35 mg risedronate sodium, blood samples were collected serially for a period of 48 hours. Plasma was analyzed for risedronate by using LC/MS/MS assay method. The analysis system was validated in specificity, accuracy, precision, and linearity. $AUC_t$, (the area under the plasma concentration-time curve from the zero-time to 48 hr) was calculated through the trapezoidal rule. $C_{max}$ (maximum plasma drug concentration) were compiled from the plasma risedronate concentration-time data of each volunteer. No significant sequence effect was found for the pharmacokinetic parameters indicating that the cross-over design was properly performed. The 90 % - Confidence intervals of the $AUC_t$ ratio and the $C_{max}$ were from log 0.8752 to log 1.1888 and log 0.8457 to log 1.1478, respectively. These values were within the acceptable intervals between 0.80 and 1.25. Therefore, this study demonstrated that no statistically significant difference was identified with respect to the rate and extent of absorption.