• Korean Journal of Clinical Pharmacy
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• v.25 no.3
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• pp.138-144
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• 2015

Objective: It is to evaluate the drug interaction monitoring program as a pilot project to develop a pharmaceutical care model in a medical intensive care unit and to analyze the influencing factors of drug interactions. Method: Electronic medical records were retrospectively investigated for 116 patients who had been hospitalized in a medical intensive care unit from October to December in 2014. The prevalence of adverse reaction with risk rating higher than 'D' was investigated by Lexi-$Comp^{(R)}$ Online database. The factors related with potential drug interaction and with treatment outcomes were analyzed. Results: The number of patients with a potential interaction of drug combination was 92 (79.3%). Average ages, the length of stay in the intensive care unit and the numbers of prescription drugs showed significant differences between drug interaction group and non-drug interaction group. Opioids (14.4%), antibiotics (7.2%), and diuretics (7.2%) were most responsible drug classes for drug interactions and the individual medications included furosemide (6.4%), tramadol (4.9%), and remifentanil (4.5%). There were 950 cases with a risk rating of 'C' (84.6%), 142 cases with a risk rating of 'D' (12.6%), and 31 cases with a risk rating of 'X' (avoid combination) (2.8%). The factors affecting drug interactions were the number of drugs prescribed (p < 0.0001) and the length of stay at intensive care unit (p < 0.01). The patients in intensive care unit showed a high incidence of adverse reactions related to potential drug interaction. Therefore, drug interaction monitoring program as a one of pharmaceutical care services was successfully piloted and it showed to prevent adverse reaction and to improve therapeutic outcomes. Conclusion: Active participation of a pharmacist in the drug management at the intensive care unit should be considered.

• Korean Journal of Clinical Pharmacy
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• v.29 no.2
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• pp.89-100
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• 2019

Background: Invasive aspergillosis (IA) is associated with high morbidity and mortality, particularly among immunocompromised patients, such as lung transplant recipients. Voriconazole, the first-line therapy for IA, shows a non-linear pharmacokinetic profile and has a narrow therapeutic range. Careful and appropriate administration is necessary, primarily because it is used for critically ill patients; however, the clinical usefulness of therapeutic drug monitoring (TDM) has not been sufficiently verified. Therefore, in this study, we validated the safety and efficacy of voriconazole TDM in lung transplant recipients receiving only voriconazole for IA treatment. Methods: The electronic medical records of lung transplant recipients (${\geq}19$ years of age) administered only voriconazole for > 7 days for treatment of IA from June 1, 2013 to May 31, 2018 were analyzed retrospectively. Results: Among the 54 patients, 27 each were allocated to TDM and non-TDM groups, respectively. There were no significant differences in patient characteristics between the two groups except for ICU-hospitalization status. Of the TDM group patients, 81.5% needed adjustment of voriconazole dosage because the levels were out of target range. Comparison of two groups showed that treatment response was higher throughout treatment and switching rates of second-line agents were significantly lower in the TDM group, but it was insufficient to confirm safety improvements through voriconazole TDM. Conclusions: Considering that the treatment response tended to be higher and the rates of switching to second-line antifungal agents were lower in the TDM group, voriconazole TDM may increase the therapeutic effect on IA in lung transplant patients.

• YAKHAK HOEJI
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• v.42 no.2
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• pp.181-186
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• 1998

This study was attempted to investigate the pharmacokinetics of cyclosporine (10mg/kg, oral) in rabbits with $CCI_4$ and bile duct ligation-induced hepatic disorder. The area under the curve (AUC) of blood cyclosporine concentration versus time was significantly increased ($CCI_4$-induced hepatic disorder. Elimination rate constant (Kel) was significantly decreased (p<0.05, p<0.01) in rabbits with $CCI_4$ and bile duct ligation-induced hepatic disorder. Volume of distribution (Vdss) and total body clearance (CLtot) were significantly decreased (p<0.01) in rabbits with $CCI_4$-induced hepatic disorder. But Vdss was significantly increased (p4-induced hepatic disorder were 874ng/ml and 2.71 hr, respectively. Cmax and Tmax values in rabbits with bile duct ligation were 105ng/ml and 2.834 hr, respectively. From results of this experiment. It is desirable to do therapeutic drug monitoring of cyclosporine for effective treatment when the cyclosporine is administered to patients with liver disorder m clinical practice.

• Quality Improvement in Health Care
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• v.1 no.1
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• pp.32-43
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• 1994

The 'Pharmacy and Therapeutic Committee' decided to restrict the use of vancomycin which was categorized into restricted antimicrobials, among general, reserved and restricted antimicrobials. The committee also established prescribing guidelines of vancomycin in Seoul National University Hospital, May, 1991. Especially, the restricted antimicrobials should be used after approval by infectious disease specialist physician. A retrospective drug use evaluation (DUE) on vancomycin has been conducted to compare with the previous vancomycin DUE study in 1990. 'Criteria for DUE on vancomycin' was modified from Am J Hosp Pharm. Total 65 charts of patients were retrospectively reviewed from July 1991 to June 1992 in Seoul National University Children's Hospital. The justification of use was improved from 56% to 75% comparing with the previous study. In analyzing process indicators, several criteria including body temperature monitoring, WBC monitoring and use of concomitant antibiotics were well documented, but serum creatinine monitoring, culture and sensitivity test and level monitoring were infrequently performed, while the accepted level has been improved. Accepted level for appropriate initial dosage and duration of therapy were decreased. In outcome analysis, blood culture after discontinuing the drug was relatively well documented compared with the previous study. As the results, the approval vancomycin use was shown to be effective and rational in antibiotic therapy. And it is suggested that the above findings should be communicated to the medical staff, and a active intervention, such as feedback control, also be necessary for rational drug use.

• Journal of Pharmaceutical Investigation
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• v.24 no.4
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• pp.289-295
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• 1994

Pharmacokinetic drug interaction between phenytoin and verapamil was investigated following i.v. administration of two drugs concomitantly to rabbits. Verapamil was coadministered with phenytoin (5 mg/kg) to rabbits at the doses of 0.5,1 and 2 mg/kg, respectively. Plasma concentration and AUC of phenytoin were increased significantly, but volume of distribution and total body clearance were decreased significantly (p<0.05) at doses of 1mg and 2mg/kg of verapamil, respectively. From the results of this experiment, it is desirable that dosage regimen of phenytoin should be adjusted and that therapeutic drug monitoring should be performed for reduction of side or toxic effect when phenytoin should be administered with verapamil in clinical practice.

• Pediatric Infection and Vaccine
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• v.21 no.1
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• pp.9-21
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• 2014

Purpose: To determine the clinical significance of voriconazole therapeutic drug monitoring (TDM) in the pediatric population. Methods: Twenty-eight patients with invasive fungal infections administered with voriconazole from July 2010 to June 2012 were investigated retrospectively. Fourteen received TDM, and 143 trough concentrations were analyzed. All 28 patients were assessed for adverse events and treatment response six weeks into treatment, and at the end. Results: Out of 143 samples, 53.1% were within therapeutic range (1.0-5.5 mg/L). Patients administered with the same loading (6 mg/kg/dose) and maintenance (4 mg/kg/dose) dosages prior to initial TDM showed highly variable drug levels. Adverse events occurred in 9 of 14 patients (64.3%) in both the TDM and non-TDM group. In the TDM group, voriconazole-related encephalopathy (n=2, 14.3%) and aspartate aminotransferase (AST) or alanine aminotransferase (ALT) elevation (n=8, 57.1 %) occurred with serum levels in the toxic range (>5.5 mg/L), whereas blurred-vision (n=2, 14.3%) occurred within the therapeutic range (1.18 mg/L and 3.9 mg/L). The frequency of voriconazole discontinuation due to adverse events was lower in the TDM group (0.0% vs. 18.2%, P =0.481). Overall, 57.2% of the patients in the TDM group versus 14.3% in the non-TDM group showed clinical response after 6 weeks (P =0.055), whereas 21.4% in the TDM group versus 14.3% in the non-TDM group showed response at final outcome (P =0.664). In the TDM group, >67.0% of the serum levels were within therapeutic range for the first 6 weeks; however 45.5% were within therapeutic range for the entire duration. Conclusion: Routine TDM is recommended for optimizing the therapeutic effects of voriconazole.

• Journal of Pharmaceutical Investigation
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• v.23 no.1
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• pp.27-32
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• 1993

Pharmacokinetic drug interaction between phenytoin and diltiazem was investigated following i.v. administration concomitantly to rabbits. Diltiazem was coadministered at doses of 1, 2 and 3 mg/kg, respectively, with phenytoin (5 mg/kg) to rabbits. Plasma concentration and AUC of phenytoin were increased significantly, but volume of distribution and total body clearance were decreased significantly (p<0.05) at doses of 2 mg and 3 mg/kg of diltiazem. From the results of this experiment, it is desirable that dosage regimen of phenytoin should be adjusted and that therapeutic drug monitoring should be practiced for reduction of side or toxic effect when phenytoin should be administered with diltiazem in clinical practice.

• Journal of Pharmaceutical Investigation
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• v.39 no.2
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• pp.111-115
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• 2009

The pharmacokinetics of cyclosporin A (CsA) after single and multiple oral dosing of new CsA self-micro-emulsifying drug delivery system (SMEDDS) in dogs were estimated. A single dose study was performed following a two-way crossover design against six dogs with reference SMEDDS. For a multiple dose study, three dogs were allocated for each drug, and 100 mg of drug was administered daily for 6 days. Whole blood concentration of CsA was analyzed by radio-immunoassay. Both drug showed identical blood concentration profiles in both studies, and no statistical difference was detected in pharmacokinetic parameters. The relative bioavailabilities of test SMEDDS were 91.4% and 89.1%, respectively, in the single dose study and the last day of multiple dose study. Especially, multiple dose study proved the good relationship between C-0/C-2 and AUC for reference SMEDDS, which is an indispensable part of therapeutic drug monitoring. These results suggest newly formulated CsA SMEDDS possibly shows identical pharmacokinetics and pharmacodynamic behaviors in clinical trials.

• Translational and Clinical Pharmacology
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• v.26 no.3
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• pp.134-140
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• 2018

This study aimed to develop a UPLC-MS/MS method for determining plasma levels of L-aspartic acid and L-asparagine and the activity of L-asparaginase. L-aspartic acid, L-asparagine, and L-aspartic acid-2,3,3-$d_3$ were extracted from human plasma by protein precipitation with sulfosalicylic acid (30%, v/v). The plasma samples were analyzed using an Imtakt Intrada amino acid analysis column with 25 mM ammonium formate and 0.5% formic acid in acetonitrile as the mobile phase with step gradient method at a flow rate of 0.5 mL/min. The injection volume was $5{\mu}L$, and the total run time was 15 min. Inter- and intra-batch accuracies (%) ranged from 96.62-106.0% for L-aspartic acid and 89.85-104.8%, for L-asparagine, and the coefficient of variation (CV%) did not exceed 7%. The validation results for L-aspartic acid and L-asparagine satisfied the specified criterion, however, the results for L-asparaginase activity assay showed a borderline validity. This study could be a foundation for further development of therapeutic drug monitoring systems using UPLC-MS/MS.

• Korean Journal of Clinical Pharmacy
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• v.30 no.3
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• pp.143-148
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• 2020

Objective: This study aimed to investigate pharmaceutical care for critically ill neonates and suggest targeted strategies compatible with the Korean health-system pharmacy. Methods: Articles that reported pharmacy practices for critically ill neonates were reviewed. Pharmaceutical care practices and roles of neonatal pharmacists were identified, and criteria were developed for neonates in need of specialized care by clinical pharmacists. Results: Neonatal pharmacists play many roles in the overall medication management pathway. For clinical decision support, multidisciplinary ward rounds, clinical pharmacokinetic services, and consultation for pharmacotherapy and nutrition support were conducted. Prevention and resolution of drug-related problems through review of medication charts contributed to medication safety. Pharmaceutical optimization of intravenous medication played an important role in safe and effective therapy. Information on the use of off-label medicine, recommended dosage and dosing schedules, and stability of intravenous medicine was provided to other health professionals. Most clinical practices for neonates in Korea included therapeutic drug monitoring and nutrition support services. Reduction in medication errors and adverse drug reactions, shortening the duration of weaning medicines, decreasing the use and cost of antimicrobials, and improvement in nutrition status were reported as the outcomes of pharmacist-led interventions. The essential criteria of pharmaceutical care, including for patients with potential high-risk factors for drug-related problems, was developed. Conclusion: Pharmaceutical care for critically ill neonates varies widely. Development and provision of standardized pharmaceutical care for Korean neonates and a stepwise strategy for the expansion of clinical pharmacy services are required.