• Archives of Pharmacal Research
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• 제18권6호
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• pp.385-390
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• 1995

The analytical methods for the analysis of cyclosporine (CsA), a fluorescence polarization immunoassay (FPIA) and HPLC method, were compared in a pharmacokinetic study of two CsA soft capsule formultaions ($Sandimmun^{\circledR}$; Sandoz, $Implanta^{\circledR}$; Hanmi). Sixteen healthy volunteers completed the study and each subjected single doses ($4{\tiems}100$ mg) of the test and the reference formulations in a two-way crossover design with a one-week drug-free interval between doses. Following each administration, whole blood concentrations of CsA were monitored over a period of 24 hour by both FPIA and HPLC methods. Blood concentrations nad pharmacokinetic parameters determined by either analytical method showed large intersubject variation, with the FPIA data showing relatively higher magnitude of intersubjecte variation than the HPLC data. The blood concentrations determined by FPIA were 1.1-1.3 times higher than those determined by HPLC. There were strong and significant correlations between the two methods (r>0.83 : p<0.0001). Intersubuject variation for the $AUC_{inf}{\;}and{\;}AUC_{24hr}$ of the test formulation was slightly reduced without statistical significance (paried -t test : p>0.05 $t_{max}$ was earlier nad $C_{max}$ was slightly lower for the test formulation, $AUC_{24h}, {\;}C_{max}, {\;}T_{max}$ and MRT determined separately from the data obtained by the two methods for the two formulations were examined by analyses of variance (ANOVA) for the bioequivalency evaluation. Results of ANOVA and confidence limits of terst/reference ratios of $AUC_{24th}$, $C_{max}$, $t_{max}$ and MRT, and statistical tests indicated the bioequivalence of the two formulations (i.e., test/reference ratio was within $100{\times}20%$) except for $C_{max}$ and $t_{max}$. The mean of tmax also showed 11.1% and 9.3% differences but the detection limit were 29.2% and 29.6% as determined by FPIA and HPLC resepctively. This experiments suggest that the data yielded for the two formulations demonstrated that they were bioequivalent.

• Journal of Oral Medicine and Pain
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• 제40권1호
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• pp.10-16
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• 2015

Purpose: Pilocarpine has the effects on improvement of salivary flow and subjective symptoms for xerostomic patients. Because of unwanted side effects following its systemic administration, topical pilocarpine has been paid attention as an alternative. This study aimed to investigate effects of pilocarpine solution as mouthwash on salivary flow and adverse effects compared to systemic administration of 5 mg pilocarpine tablet in healthy subjects. Methods: The study was a double blind, placebo-controlled, crossover clinical trial. Five milligrams pilocarpine tablets, 4 mL of 2% pilocarpine solution and placebo solution were given to 12 healthy volunteers (6 males and 6 females) in a predetermined order with wash-out period of at least two days and unstimulated whole saliva was collected before and after administration of each drug. Blood pressure and pulse rate was also measured and subjective effect and potential side effects were evaluated by a self-administrated questionnaire. Results: Systemic (5 mg tablet) and topical (2% solution) use of pilocarpine significantly increased salivary flow rate in healthy subjects compared to placebo (p<0.001). In both the pilocarpine solution and tablet groups, salivary flow rates at 120 minutes after administration remained increased. Subjective effect on salivation was the largest in the pilocarpine tablet group, followed by the pilocarpine solution group (p<0.05). There was no significant difference in blood pressure and pulse rate after administration of all three drugs. Fewer side effects reported in the pilocarpine solution group than in the tablet group. Conclusions: Two percents pilocarpine solution as mouthwash increases salivary flow rate, definitely superior to placebo solution and comparable to pilocarpine tablet, with fewer side effects in healthy subjects. It indicates a possibility of pilocarpine solution as a useful alternative of pilocarpine tablets for the xerostomic patients with systemic diseases.

• Journal of Pharmaceutical Investigation
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• 제28권1호
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• pp.35-42
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• 1998

A $3{\times}3$ Latin square crossover study for the bioequivalence of three ondansetron formulations was conducted. Test products were $Vominon^{\circledR}$ 8 mg and $Vominon^{\circledR}$ 4 mg tablets and reference product was $Zofran^{\circledR}$ tablet. Twenty one healthy Korean male subjects received each formulation at the ondansetron dose of 8 mg and plasma concentrations of ondansetron were monitored by HPLC for over a period of 12 hr after the oral administration. Statistical procedure for bioequivalence evaluation of AUC {e.g., analysis of variance (ANOVA), multiple comparison and confidence intervals} was carried out. There were no significant differences in AUC among the formulations. The confidence intervals for the AUC of $Vominon^{\circledR}$ 8 mg and $Vominon^{\circledR}$ 4 mg were between -0.24 and 15.54% and between -2.41 and 13.36% respectively, within a range that proposed by the Korea Food and Drug Administration Guidelines for Bioequivalence. These statistical procedure could be standardized and generally applicable for the assessment of bioequivalence for multiple (more than two) formulations.

• 한국군사과학기술학회지
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• 제20권4호
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• pp.587-596
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• 2017

In this study, multi-chambered single autoinjector(2in1) and KMARK-1 containing atropine and 2-PAM(pyridine-2-aldoxime methylchloride) were administered to the beagle's muscle, and blood samples were taken for a certain period of time to compare and evaluate the pharmacokinetic profiles of the two drugs. Male beagles were used and classified into two test groups(G1, G2), and crossover pharmacokinetic studies were performed in two test groups. Blood samples were collected from the jugular vein for analysis after administration. The 90 % confidence interval(CI) for log transformed data indicated that the Cmax for both atropine(log 0.9683 ~ log 1.113) and 2-PAM(log 0.9453 ~ log 1.214) was within the limits of bioequivalence criteria, but the AUC for atropine(log 1.1786 ~ log 1.3238) failed to meet this criteria. This is expected as the amount of atropine dose is 25 % higher for the test as compared to the reference formulation. In summary, in view of the ATNAA(antidote for nerve agent of US) authorization, the Cmax equivalence was more important than AUC equivalence, so in this study, we also focused on verifying the equality of Cmax between the two autoinjectors.

• 응용통계연구
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• 제28권2호
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• pp.289-294
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• 2015

생동성 시험과 같은 임상약리학분야의 연구는 일반적으로 한 개체 내에서 반복하여 측정된 자료구조를 사용하므로 선형혼합모형을 이용하여 분석하는 것이 보편적이다. 이러한 모형에서 랜덤효과는 개체 내 관측 자료 사이의 상관관계를 설명하고, 공분산행렬은 개체-내 변동을 설명한다. 생동성 분석은 두 약물의 약동학적 변수인 Cmax와 AUC의 기하평균비에 대한 90% 신뢰구간이 동등성 한계인 [0.8, 1.25] 범위에 드는지 알아보는 분석으로, 고정효과에는 시기, 순서군, 치료효과를, 랜덤효과에는 개체효과를 가지는 선형혼합모형을 이용하여 분석한다. 이러한 분석이 적용된 실제 예를 살펴보기 위하여 레보플록사신 연구의 자료를 활용하였다.

• Biomolecules & Therapeutics
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• 제7권1호
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• pp.59-65
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• 1999

A bioequivalence study of the Dong Wha Cisapril tablets(Dong Wha Pharm. Ind. Co., Ltd.) to the Prepulsid tablets(Janssen Korea Ltd.), formulations of cisapride, was conducted. Twenty four healthy Korean male subjects received each formulation at the dose of 5 mg as cisapride in a 2$\times$2 crossover study. There was a 1-week washout period between the doses. Plasma concentrations of cisapride were monitored by an LC/MS method for over a period of 36 h after each administration. AUC(area under the plasma concentration- time curve from time zero to infinity) was calculated by the linear trapezoidal and extrapolation method. $C_{max}$ (maximum plasma drug concentration) and $T_{max}$ (time to reach $C_{max}$) were compiled from the plasma drug concentration-time data. Analysis of variance (ANOVA) revealed that there are no differences in AUC, $C_{max}$ and $T_{max}$ between the formulations. The apparent differences between the formulations in these parameters were all far less than 20% (i.e., 6.8, -6.6 and 1.8% for AUC, $C_{max}$ and $T_{max}$, respectively). Minimum detectable differences(%) at $\alpha$=0.05 and 1-$\beta$=0.8 were all less than 20% in these parameters between the formulations (i.e., 16.5, 11.4 and 16.4% for AUC, $C_{max}$ and $T_{max}$, respectively). The 90% confidence intervals for these parameters were also within 20% (i.e., -2.9~ 16.4, -13.2~0.1 and -7.8~ 11.4% for AUC, $C_{max}$ and $T_{max}$, respectively). These results satisfy the bioequivalence criteria of the Korea Food and Drug Administration (KFDA) guidelines (No. 98-51). Therefore, these results indicate that the two formulations of cisapride are bioequivalent and, thus, may be prescribed interchangeably.hangeably.y.hangeably.

• 한국산학기술학회논문지
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• 제17권9호
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• pp.458-463
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• 2016

융합의 개념은 효율과 성능 개선 등을 목적으로 서로 다른 기술이나 산업분야가 결합함으로써 존재하지 않았던 새로운 기능이나 서비스를 창출하는 현상을 말한다. 우리가 사는 지금 이 시대는 기술의 비약적인 발달로 인해 컨텐츠 생산 및 소비 환경이 급격히 변화하고 있으며, 각 분야의 경계가 소멸하는 방향으로 진행되고 있다. 이는 음악에도 적용된다. 1969년 재즈 연주자 마일스 데이비스에 의해 재즈와 록음악의 융합이 시도되었고, 클래식 또한 예외는 아니었다. 장르간의 크로스오버를 통해 엄격하게만 연주되었던 클래식은 그 틀을 벗어나 새로운 형식으로 거듭나게 되었다. 이러한 추세는 전 세계적으로 확산되었으며, 한국에서도 여러 뮤지션들에 의해 크로스오버가 시도되었다. 본 논문에서는 대중음악의 편곡기법을 활용하여 클래식 음악을 연주한 사례로, 1979년에 발표된 사랑과 평화 1집에 수록된 <여왕벌의 비행>, <베에토벤의 운명> 두 곡을 선정하였다. 각각의 곡은 원곡의 악보와 함께 나열하고 클래식과 훵크의 특징을 리듬섹션을 중심으로 분석하였다.

• 한국지진공학회논문집
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• 제7권4호
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• pp.1-13
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• 2003

본 연구에서는 전단변형을 고려한 비대칭 박벽 곡선보의 자유진동해석을 수행할 수 있는 일반이론을 제시하기 위하여, 3차원 연속체에 대한 가상일의 원리로부터 전단변형 효과를 고려하고 비대칭 박벽단면과 ？(Warping)을 포함하는 변위장을 도심 축에 대해 정의한 후 곡선보의 변형도-변위관계로부터 공간 박벽 곡선보의 일반화된 탄성변형에너지와 운동에너지를 새롭게 유도한다. 또한, 전단변형이 고려된 곡선보의 총포텐셜에너지에 대해 변분을 취함으로써 평형방정식과 힘-변위관계를 제시한다. 한편, 제시된 이론에 대해 등매개 보요소를 도입하여 유한요소 정식화를 수행하였으며 곡선보의 동적 거동특성을 조사하기 위하여 전단변형, 곡률효과 그리고 진동모드에 대한 매개변수 연구를 수행한다. 마지막으로, 본 연구의 타당성을 입증하기 위하여, 다양한 해석예제에 대한 3차원 고유진동수를 산정하고 타 연구자들의 결과 및 ABAQUS의 쉘요소를 이용한 해석결과와 비교ㆍ검증한다.

• Journal of Dental Anesthesia and Pain Medicine
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• 제19권2호
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• pp.101-109
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• 2019

Background: The purpose of this study was to compare the pain perception and anesthetic efficacy of 2% lignocaine with 1:200,000 epinephrine, buffered lignocaine, and 4% articaine with 1:200,000 epinephrine for the inferior alveolar nerve block. Methods: This was a double-blind crossover study involving 48 children aged 5-10 years, who received three inferior alveolar nerve block injections in three appointments scheduled one week apart from the next. Pain on injection was assessed using the Wong-Baker Faces pain scale and the sound eye motor scale (SEM). Efficacy of anesthesia was assessed by subjective (tingling or numbness of the lip, tongue, and corner of mouth) and objective signs (pain on probing). Results: Pain perception on injection assessed with Wong-Baker scale was significantly different between buffered lignocaine and lignocaine (P < 0.001) and between buffered lignocaine and articaine (P = 0.041). The onset of anesthesia was lowest for buffered lignocaine, with a statistically significant difference between buffered lignocaine and lignocaine (P < 0.001). Moreover, the efficacy of local analgesia assessed using objective signs was significantly different between buffered lignocaine and lignocaine (P < 0.001) and between lignocaine and articaine. Conclusion: Buffered lignocaine was the least painful and the most efficacious anesthetic agent during the inferior alveolar nerve block injection in 5-10-year-old patients.

• 한국응급구조학회지
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• 제22권3호
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• pp.35-45
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• 2018

Purpose: The purpose of this study was to compare laryngoscopic views and ease of use and success of intubation, via the percentage of glottic opening (POGO) scale when using the Miller blade and Macintosh blade in paraglossal approach. Methods: Forty intern doctors were randomized for laryngoscopy to be performed in a crossover manner. They performed endotracheal intubation with Miller blade and Macintosh blade in two airway scenarios: normal airway and difficult airway with edema. We observed the rate of successful intubation, time required for visualizing the glottis, time to complete endotracheal intubation, ease of intubation, and the POGO scale. Results: In the normal airway, there was no difference in intubation between the two endoscopes. In the difficult airway, the time for visualizing the glottis (7.80 versus 10.24 sec; p=.006), the time to tube passage (19.38 versus 23.03 sec; p=.038) and the time to complete endotracheal intubation (21.84 versus 28.54 sec; p=.022) with Miller blade was shorter than with Macintosh blade. The POGO scale(%) of the Miller blade was higher than that of the Macintosh blade's (62.25 versus 56.32; p=.030). Conclusion: Compared to the Macintosh blade, Miller blade provided better visualization of the glottis and POGO scale, and faster time to completion of endotracheal intubation.