• Korean Journal of Biological Psychiatry
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• v.5 no.1
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• pp.56-65
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• 1998

Clinicians can use therapeutic drug monitoring(TDM) to optimise dosage decisions with psychotropic drugs, in order to maximize efficacy and prevent toxicity, especially when individuals are nonresponsive to treatment or vulnerable to adverse reactions with standard doses because age, disease states or drug interactions. Currently, therapeutic drug concentrations have been established for the TCA and lithium. There is also evidence for the usefulness of TDM with carbamazepine, valproic acid and some antipsychotic drugs. However for most psychotropic drugs this approach remains experimental. TDM-assisted psychiatric treatment is potentially useful and cost effective, particularly when applied by psychiatrists who are knowledgeable of pharmacokinetics and pharmacodynamics.

• Korean Journal of Clinical Pharmacy
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• v.19 no.2
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• pp.120-130
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• 2009

The objective of this study was to analyze and to improve therapeutic drug monitoring(TDM) service of vancomycin in a local hospital. Patients with TDM service between September 2005 and December 2008 were included and the data were collected for vancomycin use and components of TDM. During that period, 421 cases of TDM service of vancomycin in 236 patients were retrospectively reviewed. The first dosages of vancomycin were appropriate in 135(57.2%) patients and administration of vancomycin was discontinued in 126(53.4%) patients due to therapeutic failure or adverse drug reaction. MRSA was identified in 191(80.9%) patients and 135(70.7%) samples for the identification were sputum. According to the TDM reports, 232(55.1%) serum samples were obtained at the steady-state conditions and 55.5% of the samples that were drawn before the steady-state was due to the physician's inappropriate knowledge about the steady-state. Based on the time of vancomycin administration, 35.8% of the samples were not obtained at the recommended sampling time. For the patients in general wards, the most common reason for the incorrect samples was routine serum sampling by the laboratory medicine phlebotomists between 6 and 8 a.m. except sunday. In contrast, samples drawn by nurses or physicians at inappropriate time were the most common reason for the incorrect samples with patients in the intensive care units. Physicians accepted 68.5% of the recommendations for vancomycin dosage and administration. In conclusion, TDM service of vancomycin needs to be improved in inappropriate sampling time and vancomycin dosage. For solving these problems, current team made of TDM pharmacists and physicians of laboratory medicine can be expanded to include a physician of infectious diseases, nurses and laboratory medicine phlebotomists as new members. Through the TDM service of vancomycin by the new team, we can settle the problems and make the guideline for the scientific controversies associated with therapeutic monitoring of vancomycin.

• Korean Journal of Clinical Pharmacy
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• v.11 no.1
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• pp.1-6
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• 2001

This research is conducted to evaluate the clinical and economic benefits from therapeutic drug monitoring(TDM) service on vancomycin in a tertiary general hospital. Total 99 pairs of steady state peak and trough concentrations of vancomycin were obtained from 73 patients. To see the clinical benefits, the appropriateness of vancomycin dosing before TDM was evaluated. In 72 pairs of vancomycin blood concentrations obtained prior to TDM consultation, $47.2\%$ of the cases had reached within therapeutic range. Serum vancomycin levels in patients with $40{\leq}CLcr<60$ (ml/min) were higher and than the levels in patients with 40>CLcr and $60{\leq}CLcr$ (ml/min). Dose reduction rate in patients with creatinine clearance $40{\leq}CLcr<60$ (ml/min) were also significantly higher than those of compared groups ($61.5\%$, p=0.0138). Serum vancomycin concentrations were re-obtained from 21 patients who received modified dose through TDM service. Ninety percent (19/21cases) of them were within the target therapeutic range. For the evaluation of economic benefits from TDM consultation, estimated cost savings were calculated in those patients. The total drug saving were 586 vials in 21 patients. The calculated mean cost saving from the drugs was 314,570 won (range: $11,273\sim473,466)$ per patient. The study revealed that TDM service for vancomycin is necessary because empirical dosing is not effective for obtaining therapeutic drug level, especially patients with mild renal insufficiencies. The cost saving from TDM is also beneficial for the patients.

• 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.

• Tuberculosis and Respiratory Diseases
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• v.78 no.2
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• pp.78-84
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• 2015

Background: Reports of therapeutic drug monitoring (TDM) for second-line medications to treat multidrug-resistant tuberculosis (MDR-TB) remain limited. Methods: A retrospective cohort from the Virginia state tuberculosis (TB) registry, 2009-2014, was analyzed for TDM usage in MDR-TB. Drug concentrations, measured at time of estimated peak ($C_{max}$), were compared to expected ranges. Results: Of 10 patients with MDR-TB, 8 (80%) had TDM for at least one drug (maximum 6 drugs). Second-line drugs tested were cycloserine in seven patients (mean $C_{2hr}$, $16.6{\pm}10.2{\mu}g/mL$; 4 [57%] below expected range); moxifloxacin in five (mean $C_{2hr}$, $3.2{\pm}1.5{\mu}g/mL$; 1 [20%] below); capreomycin in five (mean $C_{2hr}$, $21.5{\pm}14.0{\mu}g/mL$; 3 [60%] below); para-aminosalicylic acid in five (mean $C_{6hr}$, $65.0{\pm}29.1{\mu}g/mL$; all within or above); linezolid in three (mean $C_{2hr}$, $11.4{\pm}4.1{\mu}g/mL$, 1 [33%] below); amikacin in two (mean $C_{2hr}$, $35.3{\pm}3.7{\mu}g/mL$; 1 [50%] below); ethionamide in one ($C_{2hr}$, $1.49{\mu}g/mL$, within expected). Two patients died: a 38-year-old woman with human immunodeficiency virus/acquired immune deficiency syndrome and TB meningitis without TDM, and a 76-year-old man with fluoroquinolone-resistant (pre-extensively drug-resistant) pulmonary TB and low linezolid and capreomycin concentrations. Conclusion: Individual pharmacokinetic variability was common. A more standardized approach to TDM for MDR-TB may limit over-testing and maximize therapeutic gain.

• 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.

• The Korean Journal of Physiology and Pharmacology
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• v.15 no.2
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• pp.67-81
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• 2011

Epilepsy is a chronic disease occurring in approximately 1.0% of the world's population. About 30% of the epileptic patients treated with availably antiepileptic drugs (AEDs) continue to have seizures and are considered therapy-resistant or refractory patients. The ultimate goal for the use of AEDs is complete cessation of seizures without side effects. Because of a narrow therapeutic index of AEDs, a complete understanding of its clinical pharmacokinetics is essential for understanding of the pharmacodynamics of these drugs. These drug concentrations in biological fluids serve as surrogate markers and can be used to guide or target drug dosing. Because early studies demonstrated clinical and/or electroencephalographic correlations with serum concentrations of several AEDs, It has been almost 50 years since clinicians started using plasma concentrations of AEDs to optimize pharmacotherapy in patients with epilepsy. Therefore, validated analytical method for concentrations of AEDs in biological fluids is a necessity in order to explore pharmacokinetics, bioequivalence and TDM in various clinical situations. There are hundreds of published articles on the analysis of specific AEDs by a wide variety of analytical methods in biological samples have appears over the past decade. This review intends to provide an updated, concise overview on the modern method development for monitoring AEDs for pharmacokinetic studies, bioequivalence and therapeutic drug monitoring.

• Proceedings of the Korean Society of Applied Pharmacology
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• 1997.11a
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• pp.93-106
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• 1997

약물 투여 후 약효의 출현은 흡수, 분포 등의 약동학적 단계(pharmacokinetic phase)를 거쳐 수용체 부위에서 약물과 수용체 사이의 약력학적(pharmacodynamic) 상호작용에 의해 나타난다. 따라서 약물요법 시 약효나 독성 발현의 큰 개인차는 약동학적 또는 약력학적 개인차에 의해 나타나며, 많은 약물에서 약효의 개인차는 흔히 약동학적 차이가 주역할을 함이 알려져 있고, 약물의 특성에 따라 약물의 대사 및 배설과 관련 있는 신장, 간장 및 심장 질환자에서는 현저한 약동학적 변화로 용법 조정이 필수적으로 요구되는 경우가 많다. 약동학적 개인차는 안전역이 좁은 약물에서 더욱 문제가 되며 이러한 약물의 적정 요법을 위해서는 수용체 부위와 평형을 이루고 있는 혈장약물농도를 적정 유지하는 것이 약동학적 개체차를 배제할 수 있는 한 방안이다. 근자에 이르러 체액내 약물 및 이의 대사물을 측정하는 분석 화학의 발전과, 임상 약물 동태학(clinical pharmacokinetics)의 도입 등으로 개개 환자에서의 적정 약물요법을 위한 TDM (Therapeutic Drug Monitoring)이 구미에서는 이미 보편화되어 있다 또한 국내에서도 이러한 새로운 의료분야의 연구 및 임상응용의 필요성이 점차 증가하고 있으므로, 이러한 시대적 요구에 발맞추어 본 지면을 통하여 임상약리학적 지식을 이용한 혈장 농도 데이터의 분석을 통하여 개개인에서의 적정 약물요법을 제시하는 TDM에 관하여 소개하고자 한다.