• 식품보건융합연구
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• 제5권4호
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• pp.13-17
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• 2019

Amiodarone hydrochloride is an antiarrhythmic agent which has low aqueous solubility and presents bioavailability problem. These properties are a challenge for the pharmaceutical industry. Inclusion of lipophilic compound in the hydrophobic core of micelles, i.e. self-assembled structures based on surfactants in aqueous solution, is one way of increasing the solubility. Intravenous formulation of amiodarone hydrochloride with polysorbate 80 as a detergent and benzyl alcohol as a co-solvent is used in medical practice. This paper aimed to study the effect of polysorbate 80 and benzyl alcohol on the water solubility of amiodarone hydrochloride. Formation of mixed micelles consisting of nonionic surfactant polysorbate 80 and cationic amiodarone with chloride counterion was investigated by fluorescence spectroscopy. Benzyl alcohol was found to decrease the stability of the mixed micelles and lead to crystallization of amiodarone hydrochloride. The greatest amounts of crystals formed at 4℃ for 30 days in the model drug solutions with polysorbate 80 concentrations of 100.1 mg/mL and 97.9 mg/mL. A change of the polysorbate 80 concentration and avoidance the use of benzyl alcohol are recommended to improve the stability of the parenteral dosage form. These results can open new perspectives in the optimization of amiodarone intravenous formulations.

• 한국임상약학회지
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• 제6권2호
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• pp.1-6
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• 1996

Carcadian rhythm dependence of vancomycin pharmacokinetics was evaluated in 5 normal volunteers receiving a single intravenous 1.0 g dose of vancomycin at 8 o'clock in the morning and another occasion at 8 o'clock in the evening in a crossover manner. The serum data were subjected to simultaneous computer nonlinear least squares regression analysis using a two-compartment pbarmacokinetic model. The mean half-life of vancomycin was $4.78\pm0.81$ hr in the morning and $4.25\pm0.51$ hr in the evening. The mean total body clearance of vancomycin was $1.29\pm0.58$ hr in the morning and $5.58\pm0.48$ hr in the evening. No circadian rhythm was found to be apparent in normal volunteers. The mean in intrasubject difference in the half-life between 8 A.M. and 8 P.M. was $15.4\%$ with fluctuations ranging from $10.4\sim33.8\%$, It is reasonable to consider individual circadian rhythm for effective dosage regimen of vancomycin in clinical chronotherapeutics.

• 한국임상약학회지
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• 제10권3호
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• pp.125-129
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• 2000

The effect of circadian rhythm on gentamicin pharmacokinetics was studied in rabbits who took a single intravenous 2 mg/kg dose of gentamicin at 09:00 in the morning (a.m.) and 22:00 in the evening (p.m.). A significant circadian rhythm of pharmacokinetic parameters as a function of time of day was noted in rabbits, showing lower total body clearance $CL_t$ and higher serum area under the curve (AUC) when given in the evening. The half-life $t_{1/2}$ was shorter in the morning $(3.88\pm0.62h)$ when compared to the evening $(4.76\pm0.75\;h)$. The AUC was greater in the evening $(25.92\pm3.49\;{\mu}g/ml{\cdot}hr)$ than that in the morning $(22.42\pm3.42\;{\mu}g/ml{\cdot}hr)$, most likely because the CLt was significantly higher when gentamicin was given in the morning $(0.18\pm0.28\;ml/hr)$ versus in the evening $(0.15\pm0.26\;ml/hr)$. The $t_{1/2}$ of gentamicin in the evening was increased significantly(p<0.05) compared to those of gentamicin in the morning. It is reasonable to consider individual circadian rhythm for effective dosage regimen of gentamicin in clinical chronotherapeutics.

• Journal of Chest Surgery
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• 제56권6호
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• pp.452-455
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• 2023

Patients who have undergone mechanical valve replacement require anticoagulation therapy with warfarin to prevent thromboembolism. However, administering warfarin to pregnant patients increases their risk of warfarin embryopathy or central nervous system disorders. Consequently, safer alternatives, such as heparin or low-molecular-weight heparin injection, are substituted for warfarin. However, limited research has been conducted on this subject, with no large-scale studies and particularly few investigations involving multiparous patients. A patient who had previously undergone mechanical mitral valve replacement for atrial septal defect and mitral stenosis received anticoagulant therapy with enoxaparin during 2 pregnancies. Upon confirmation of pregnancy, warfarin was replaced with subcutaneously injected enoxaparin with a dosage of 1 mg/kg at 12-hour intervals. The enoxaparin dosage was controlled using an anti-factor Xa assay, with a target range of 0.3-0.7 IU/mL. Intravenous heparin injections were administered starting 3 days prior to the expected delivery date and were continued until delivery, after which warfarin was resumed. No complications were observed during the deliveries.

• 대한소아치과학회지
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• 제33권4호
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• pp.710-716
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• 2006

소아치과에서 진정요법은 치과 환경에 대하여 공포를 가진 아동, 협조 전 단계의 아동, 장애를 가진 아동 그리고 구토반사 등을 보이는 환자에게 사용될 수 있다. 본 증례에서는 다발성 치아 우식증을 주소로 본원에 내원한 환아에서 1.0mg/kg 케타민과 $0.03{\sim}0.06mg/kg$ 미다졸람 그리고 아트로핀 정주 병용투여 하에 수복치료를 시행하였다. 치료시간의 연장과 적절한 진정 상태 유지를 위하여 케타민(0.33mg/kg)과 미다졸람 $1mg(0.03{\sim}0.05mg/kg)$을 혼합하거나 각각 추가 투여하였다. 지속적으로 환자의 활력징후를 관찰하면서 약물의 추가투여 용량을 결정하였다. 모니터링 장비로 맥박 산소 측정법(pulse oximetry), 전자심전도(electrocardiogram), 비혈관식혈압(NIBP : Noninvasive Blood Pressure)을 사용하여 맥박, 호흡수, 혈압, 산소 포화도 등을 측정하였다. 진료 과정동안 안전을 위해 미국 소아치과 학회(American Academy of Pediatric Dentistry ; AAPD)의 권고 사항을 준수하였다.

• Journal of Dental Anesthesia and Pain Medicine
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• 제22권2호
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• pp.117-128
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• 2022

Background: Moderate sedation is an integral part of dental care delivery. Target-controlled infusion (TCI) has the potential to improve patient safety and outcome. We compared the effects of using TCI to administer remifentanil/manual bolus midazolam with manual bolus fentanyl/midazolam administration on patient safety parameters, drug administration times, and patient recovery times. Methods: In this retrospective chart review, records of patients who underwent moderate intravenous sedation over 12 months in a private dental clinic were assessed. Patient indicators (pre-, intra-, and post-procedure noninvasive systolic and diastolic blood pressure, respiration, and heart rate) were compared using independent t-test analysis. Patient recovery time, procedure length, and midazolam dosage required were also compared between the two groups. Results: Eighty-five patient charts were included in the final analysis: 47 received TCI-remifentanil/midazolam sedation, and 38 received manual fentanyl/midazolam sedation. Among the physiological parameters, diastolic blood pressure showed slightly higher changes in the fentanyl group (P = 0.049), respiratory rate changes showed higher changes in the fentanyl group (P = 0.032), and the average EtCO₂ was slightly higher in the remifentanil group (P = 0.041). There was no significant difference in the minimum SpO₂ levels and average procedure length between the fentanyl and remifentanil TCI pump groups (P > 0.05). However, a significant difference was observed in the time required for discharge from the chair (P = 0.048), indicating that patients who received remifentanil required less time for discharge from the chair than those who received fentanyl. The dosage of midazolam used in the fentanyl group was 0.487 mg more than that in the remifentanil group; however, the difference was not significant (P > 0.05). Conclusion: The combination of TCI administered remifentanil combined with manual administered midazolam has the potential to shorten the recovery time and reduce respiration rate changes when compared to manual administration of fentanyl/midazolam. This is possibly due to either the lower midazolam dosage required with TCI remifentanil administration or achieving a stable, steady-state low dose remifentanil concentration for the duration of the procedure.

• Childhood Kidney Diseases
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• 제13권2호
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• pp.197-206
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• 2009

목적 : 소아에서 정맥용 철분 제제 투여에 대해서는 활용할 수 있는 연구 결과가 제한되어 있다. 이번 연구에서는 만성 투석 환아에게 정맥용 철분 수크로즈 제제를 투여함에 있어서 효과 및 결과 예측 인자, 안정성을 확인해 보고자 한다. 방법 : 혈청 페리틴 농도가 100 ng/mL 이하이거나 트랜스페린 포화도가 20% 이하인 21명의 만성 투석 환자가 선정되었다. 12명의 복막 투석 환자에게 철분 수크로즈를 체표면적당 200 mg의 용량으로 2주 간격으로 4회 투여하였고, 9명의 혈액 투석 환자에게 동일한 제제를 체중당 3 mg의 용량으로 일주일 간격으로 8회 투여하였다. 결과 : 치료 후 혈청 페리틴 농도는 양측 환자에서 유의한 상승을 보였고 복막 투석 환자에서는 트랜스페린 포화도가 유의한 상승을 보였다. 그러나 혈색소 수치는 양측 환자에서 모두 의미 있는 상승을 보이지는 않았다. 기저 혈색소 수치가 10 g/dL 이하이거나 기저 트랜스페린 포화도가 20% 이하인 환자는 정맥용 철분 제제 투여 후 의미있는 혈색소 상승을 보였다. 대조적으로 기저 혈색소 수치와 트랜스페린 포화도가 높았던 환자들은 치료 후 혈청 페리틴 수치의 상승을 보였다. 심각한 부작용은 없었으나 치료하는 과정에서 6명의 복막 투석 환자에서 50% 이상의 트랜스페린 포화도를 보였다. 결론 : 본 연구에서 혈액 투석 환아에서 일주일 간격으로 체중당 3 mg의 철분제제의 정맥 투여는 안전하게 사용될 수 있음을 확인할 수 있었던 반면, 복막 투석 환자에서 격주 간격으로 체표면적당 200 mg의 철분제제의 정맥 투여는 과도한 트랜스페린 포화도를 보일 수 있다.

• Toxicological Research
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• 제13권1_2호
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• pp.139-147
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• 1997

Four-week toxicity of EPO(erythropoietin) was investigated using New Zealand White rabbits according to the established regulations of Korean National Institute of Safety Research. Rabbits were administered intravenously seven days per week for 28 days with dosage of 0, 80, 400 and 2000IU/kg B. W./day. Animals administered with EPO showed no significant changes of body weight, water consumption and feed consumption, and no clinical signs and death. They were not significantly different from the control group in hematological and serum biochemical analysis, urinalysis, prothrombin time, and partial thromboplastin time. In this study, we concluded that EPO had no toxic effect in the New Zealand White rabbits when they were administered intravenously below 2000IU/ kg B.W./ day for 28 days.

• 대한약학회:학술대회논문집
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• 대한약학회 2002년도 Proceedings of the Convention of the Pharmaceutical Society of Korea Vol.2
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• pp.214-217
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• 2002

Cyclosporin A (CSA) is a poorly water-soluble cyclic peptide comprising 11 amino acids. It inhibits T-lymphocyte function that plays an important role in the induction of immune response. The potent immunosuppressive activity of CSA has been used for the prevention of rejection following transplantation of liver, kidney and bone marrow, etc. The use of CSA has been often limited by several disadvantages including low bioavailability, narrow therapeutic window, nephrotoxicity, hepatotoxicity and neurotoxicity. Moreover, CSA injection is limited to patients who are unable to take the oral preparations, because it has a risk of anaphylactic shock and nephrotoxicity due to Cremophor EL$\textregistered$, a solubilizing agent used in the commercial intravenous formulation. Owing to above mentioned disadvantages of commercial products, there is a great interest in the development of the alternative dosage forms. (omitted)

• Toxicological Research
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• 제14권3호
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• pp.435-441
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• 1998

Alginase$Alginase^{ⓡ}$ (Arginine esterase) is one of the snake venoms which is mainly consisted of arginine esterase and acts as a thrombus -forming inhibitor/thrombus-lysin. These present studies were performed to investigate of the acute and subacute toxicity of the Alginase$Alginase^{ⓡ}$ in rats. In acute toxicity study, rats were single administered intravenously with dosages of 0.001, 0.01. 0.1, 1 and 10U/kg B.W. and examined the number of death, clinical sign, body weight and pathological change for 7days after administration of Alginase$Alginase^{ⓡ}$. At maximum dose level (10U/kg B.W.), Alginase$Alginase^{ⓡ}$ induced symptoms of shock with cyanosis and dyspnea. But these symptoms dissappeared after 30~50 minutes and we could not find any other toxic effect in rats. Therefore, $LD_{50}$ Value of Alginase was over 10U/kg B.W. in rats. In four-week intravenous toxicity study of Alginase$Alginase^{ⓡ}$, rats were administered intravenously seven days per week for 28 days, with dosages of 0, 0.0125, 0.125 and 1.25U/kg B.W./day, respectively. Alginase$Alginase^{ⓡ}$ did not caused any death and showed any clinical signs in rats. No significant Alginase$Alginase^{ⓡ}$ -related changes were found in feed uptake, water consumption, hematology, serum biochemistry, urinalysis, ocular examination, organ weight and histopathological examination. From the results, Alginase$Alginase^{ⓡ}$ seems not to have any toxic effect in rats when it were given daily intravenous injections below the dosage 1.25U/kg B.W./day for four weeks.