• 한국임상약학회지
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• 제29권2호
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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.

• 한국임상약학회지
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• 제26권4호
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• pp.306-311
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• 2016

Objective: This study was performed to compare the changes in the blood concentrations of tacrolimus when either itraconazole or voriconazole is together with tacrolimus to prevent or treat invasive aspergillus pneumonia (IAP) in patients with lung transplants. Therefore we can compare the degree of drug-drug interactions between tacrolimus and itraconazole against tacrolimus and voriconazole. Methods: Patients who were admitted and had lung transplants in a territory referral hospital from September 2012 to May 2015 were analyzed retrospectively. The effects of itraconazole and voriconazole on the plasma concentrations of tacrolimus were analyzed. Results: Mean tacrolimus concentrations was $10.49{\pm}2.35ng/mL$ vs. $10.95{\pm}2.98ng/mL$ (p=0.722), and mean concentration of tacrolimus over the dose of tacrolimus per day was $8.510{\pm}5.890(ng/mL)/(mg/d)$ vs. $15.45{\pm}28.47(ng/mL)/(mg/d)$ (p=0.947) in itraconazole vs. voriconazole group each. The ratio of the number of the results out of target tacrolimus concentrations to the total number of tacrolimus concentration results was $18.0{\pm}13.3%$ vs. $24.4{\pm}18.5%$ (p=0.185). Conclusion: There were no significant differences between itraconzaole and voriconazole to have influences on mean concentrations of tacrolimus over tacrolimus dose per weight per day. However voriconazole tended to raise tacrolimus plasma concentrations more than itraconazole. Safer and more effective drug management to prevent and treat fungal infections should be done by therapeutic drug monitoring not only of tacrolimus but of itraconazole and voriconazole in lung transplant patients.

• Asian Pacific Journal of Cancer Prevention
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• 제13권5호
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• pp.2415-2418
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• 2012

Objective: To investigate the efficacy and safety of voriconazole in treating Chinese patients with hematological malignancies and invasive aspergillosis. Methods: From March 2007 to April 2012, patients with diagnoses confirmed by CT, GM test and/or PCR assays, were recruited into this study. Aspergillosis of all patients were treated with voriconazole 6 mg/kg intravenous infusion (iv) every 12 h for 1 day, followed by 4 mg/kg IV every 12 h for 10-15 days; Then, switch to oral administration that was 200mg every 12h for 4-12 weeks. Efficacy and safety were evaluated according to Practice Guideline of Infectious Diseases Society of America. Results: The overall response rate of 38 patients after voriconazole treatment was 81.6%. The median time to pyretolysis was 4.5 days. Treatment related side effects were mild and found in only 15.8% of cases. No treatment related deaths occurred. Conclusions: Voriconazole can considered to be a safe and effective front-line therapy to treat patients with hematological malignancies and invasive aspergillosis. Alternatively it could be used as a remedial treatment when other antifungal therapies are ineffective.

• Pediatric Infection and Vaccine
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• 제21권1호
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• pp.9-21
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• 2014

목적: 본 연구는 소아 환자들에서 voriconazole 치료적 약물 농도 모니터링의 임상적 의의를 분석하고자 하였다. 방법: 2010년 7월부터 2012년 6월까지 서울대학교병원에 입원한 18세 이하의 소아 환자들 중, 침습성 진균감염증에 대해 voriconazole 치료를 받은 증례를 후향적 의무기록 분석을 통해 분석하였다. 본 연구에 포함된 총 28명의 환자 중 14명이 약물 농도 모니터링을 받았으며, 143개의 혈중 농도 측정 값을 분석하였다. 모든 환자들에게서 치료 효과 및 독성 증상 발현 여부를 파악하였다. 결과: 143개의 혈중 농도 측정 값 중 53.1%에서 치료적 범위(1.0-5.5 mg/L) 내에 들었고, 같은 용법으로 치료받았더라도 높은 혈중 농도 변동성(high variability)을 보였다. 약물 농도 모니터링을 받았던 군(TDM 군)과 받지 않았던 군(non-TDM 군)에서 각각 14명 중 9명(64.3%)이 독성 증상을 나타냈는데, TDM 군에서 신경학적 증상(n=2, 14.3%) 및 간기능 장애(n=8, 57.1%)는 높은 voriconazole 혈중 농도(>5.5 mg/L)를 보인 환자들에게서 나타났다. 반면, 시각 장애는 혈중 농도가 치료적 범위 내에 있을 때 발현하였다(1.18 mg/L, 3.9 mg/L). TDM 군에서 non-TDM 군에 비하여 독성 증상으로 인하여 약물을 중단했던 빈도가 낮았다(0.0% vs. 18.2%, P =0.481). 치료 시작 6주 후 치료 효과를 분석해본 결과 TDM 군의 57.2%에서 치료에 대한 반응을 보였으나, non-TDM 군에서는 14.3%에서 치료 반응을 보였다(P =0.055). 최종 치료효과 분석에서는 TDM 군의 21.4%에서 치료 반응을 보였으나, non-TDM 군의 14.3%에서 치료 반응을 보였다(P =0.664). TDM 군에서 치료 시작 첫 6주 동안 혈중 약물 농도를 분석했을 때 67.0% 이상에서 치료적 범위 내에 들었으나, 치료 기간 전체를 봤을 때에는 45.5%에서 치료적 범위 내에 들었다. 결론: 소아에서 voriconazole 사용 시 치료적 약물 농도 모니터링을 통하여 치료 목표를 효과적으로 달성하고, 독성이 나타나는 것을 예방할 수 있다.

• 한국임상약학회지
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• 제31권2호
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• pp.125-135
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• 2021

Background: Generally, pharmacokinetics (PK) models could be stratified into two models. The compartment PK model uses the concept of simple compartmentalization to describe complex bodies, and the physiologically based pharmacokinetic (PBPK) model describes the body using multi-compartment networking. Notwithstanding sharing a theoretical background in both models, there was still a lack of knowledge to enhance compatibility in both models. Objective: This study aimed to evaluate the compatibility among PBPK, lumping model and compartment PK model with voriconazole PK case study. Methods: The number of compartments and blood flow on each tissue in the PBPK model were modified using the lumping method, considering physiological similarities. The concentration-time profiles and area under the concentration-time curve (AUC) parameters were simulated at each model, assuming taken voriconazole oral 400 mg single dose. After that, those mentioned PK parameters were compared. Results: The PK profiles and parameters of voriconazole in the three models were similar that proves their compatibility. The AUC of central compartment in the PBPK and lumping model was within a 2-fold range compared to those in the 2- compartment model. The AUC of non-eliminating tissues compartment in the PBPK model was similar to those in the lumping model. Conclusion: Regarding the compatibility of the three PK models, the utilization of the lumping method was confirmed by suggesting its reliable PK parameters with PBPK and compartment PK models. Further case studies are recommended to confirm our findings.

• 한국임상약학회지
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• 제33권2호
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• pp.113-121
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• 2023

Background: Globally, the number of patients with aspergillosis is increasing, and the mortality rate remains high. This study aimed to investigate prescribing patterns of antifungal drugs for patients with aspergillosis in South Korea using real-world data. Methods: This retrospective cross-sectional study was performed using National Patient Sample (NPS) data collected by the Health Insurance Review and Assessment Service (HIRA) during 2011-2020. The use of antifungal drugs in patients with aspergillosis was investigated. Results:A total of 1374 patients were identified: 333 patients with invasive pulmonary aspergillosis (IPA) (24.2%), 436 patients with other PA (31.7%), 73 patients with other forms of aspergillosis (5.3%), and 532 patients with unspecified aspergillosis (38.7%). The odds of receiving an antifungal prescription were higher for IPA than for other PA (aOR, 0.233; p<0.001), and higher for hematologic malignancies than for respiratory disorders other than cancer or infections (aOR, 10.018; p<0.001). During each hospitalization period, 56.1% (97/173) and 6.4% (11/173) of IPA hospitalizations received voriconazole and itraconazole monotherapy, respectively, whereas 44.3% (27/61) and 27.9% (17/61) of other PA hospitalizations received itraconazole and voriconazole monotherapy, respectively. Among outpatients with IPA, 67.5% (85/126) and 26.2% (33/126) received voriconazole and itraconazole alone, respectively, whereas among outpatients with other PA, 86.1% (68/79) and 12.7% (10/79) received itraconazole and voriconazole alone, respectively, during the year. Conclusion: In Korea, voriconazole monotherapy was preferred in IPA inpatients, and itraconazole monotherapy was preferred in other PA inpatients. In the ambulatory care settings for IPA and other PA, itraconazole monotherapy was preferred.

• 대한임상검사과학회지
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• 제54권2호
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• pp.133-141
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• 2022

혈류 감염(BSI)의 주요 원인균의 하나로 입원환자에서 이환율과 사망률을 높이는 칸디다의 항진균제 내성률을 조사하여 칸디다 혈증(candidemia)의 경험적 치료 방침에 중요한 정보를 제공하고자 한다. 2009~2018년 S병원의 혈액배양 검사에서 분리된 Candida 균주(973건) 중 Candida spp. (932 균주)에 대한 fluconazole 감수성 시험결과에서 4.7% (N=44)가 내성(resistant, R)을 보였고 C. albicans, C. parapsilosis, C. tropicalis, C. glabrata에서 내성 균주를 확인하였다. 또한, Candida spp. (947 균주)의 amphotericin B에 대한 감수성 결과에서는 내성(N=6, 0.6%)이 나타났고, 전체 Candida spp.(973 균주)에 대한 flucytosine 감수성 시험에서는 내성(N=23, 2.4%)을 보였다. Candida spp. (768 균주)의 voriconazole에 대한 감수성 시험에서는 내성(N=24, 3.1%)을 보였다. C. albicans는 fluconazole (N=23, 6.9%), voriconazole (N=21, 6.0%)이 내성이고 통계학적으로 C. albicans과 non-albicans Candida species은 fluconazole (P=0.039), voriconazole (P<0.001)로 나타났다. 칸디다 혈증의 감염률을 이해하고 예방하기 위한 감시 시스템이 요구되고 항진균제의 적절한 투여와 치료가 요구된다. 따라서 항진균제 감수성 결과의 모니터링을 통한 칸디다의 내성을 추적하는 감염감시활동 정책이 필요할 것으로 사료된다.

• Journal of Veterinary Science
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• 제24권2호
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• pp.30.1-30.6
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• 2023

A 4-year-old Chihuahua dog was referred for bilateral corneal ulcers. Slightly raised white fluorescein-positive plaque-like corneal lesions in both eyes appeared as intense hyperreflective areas with posterior shadowing on optical coherence tomography (OCT). Based on corneal cytology and culture, Candida albicans-induced fungal keratitis was diagnosed. Despite treatment, on OCT, endothelial plaques, increased stromal infiltration thickness, vertical shapes of the ulcer edge, and necrotic stromal space were judged to be aggravation of the disease, and surgery was performed. Conjunctival grafting surgery with topical 1% voriconazole effectively resolved fungal keratitis. OCT can provide detailed and objective information related to the disease prognosis.

• Mycobiology
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• 제31권2호
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• pp.95-98
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• 2003

Aantifungal agents were tested against 30 clinical isolates of Cryptococcus neoformans var. neoformans using the NCCLS method(M27-A2). Posaconazole, itraconazole and amphotericin B had lower MIC than the remaining four antifungal agents. The MIC result for posaconazole was over 220-fold lower active than fluconazole. Fluconazole MICs for most isolates fell within the dose-dependant range. The overall MIC ranges and $MIC_{50}s$ were amphotericin B(0.03-0.25; 0.25), fluconazole(0.5-64; 16), itraconazole(0.015-1; 0.125), terbinafine(0.06->2; 1), caspofungin(8-32; 32), voriconazole(0.015-0.5; 0.25), and posaconazole(0.015-0.25; 0.06 ${\mu}g/ml$), respectively. In conclusion, the $MIC_{50}s$ of these drugs did not exhibit any sign of an upward shift with the exception of fluconazole and tendency cross-resistance between the seven drugs was not observed. We conclude that in vitro resistance to antifungal agents has not significantly changed despite the recent wide-spread use of triazoles for long-term treatment of Cryptococcal meningitis.

• Clinical and Experimental Pediatrics
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• 제53권6호
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• pp.722-726
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• 2010

Chronic granulomatous disease (CGD) is an uncommon inherited disorder caused by mutations in any of the genes encoding subunits of the superoxide-generating phagocyte NADPH oxidase system, which is essential for killing catalase producing bacteria and fungi, such as $Aspergillus$ species, $Staphylococcus$ $aureus$, $Serratia$ $marcescens$, $Nocardia$ species and $Burkholderia$ $cepacia$. In case of a history of recurrent or persistent infections, immune deficiency should be investigated. Particularly, in the case of uncommon infections such as aspergillosis in early life, CGD should be considered. We describe here a case of CGD that presented with invasive pulmonary aspergillosis in a 2-month-old girl. We confirmed pulmonary aspergillosis noninvasively through a positive result from the culture of bronchial alveolar lavage fluid, positive serological test for $Aspergillus$ antigen and radiology results. She was successfully treated with Amphotericin B and recombinant IFN-${\gamma}$ initially. Six weeks later after discharge, she was readmitted for pneumonia. Since there were infiltrates on the right lower lung, which were considered as residual lesions, voriconazole therapy was initiated. She showed a favorable response to the treatment and follow-up CT showed regression of the pulmonary infiltrates.