소아환자의 약물혈중농도 모니터링을 통한 Voriconazole 용량 조절 분석
Analysis of Voriconazole Dose Adjustment by Therapeutic Drug Monitoring in Pediatric Patients
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Background : Voriconazole is the first-line treatment for invasive fungal infections, and therapeutic drug monitoring (TDM) is recommended because of its non-linear pharmacokinetic properties. Voriconazole was first approved for adults age 18 and older, which was subsequently approved for children with a maintenance dose of 7 mg/kg twice daily. However, dosing which is approved by the Korean Ministry of Food and Drug Safety (MFDS) was changed in 2013 to 9 mg/kg loading dose and 8 mg/kg maintenance dose, and the TDM criteria has not been validated for children. Thus, the purpose of this study was to confirm the effectiveness of the recommended dose by the MFDS and to contribute to establishing pediatric voriconazole dose guidelines by analyzing dose adjustment through the TDM. Methods : We retrospectively analyzed the TDM results of 32 children younger than age 18 who received voriconazole for the treatment of invasive fungal infection at Severance Hospital October 2016-June 2019. The therapeutic range of voriconazole was set to 1-5.5 mg/L. Results : A total of 32 patients were enrolled in this study and 101 TDM samples were collected (IV 52, PO 49). The mean of Ctrough was 2.43 ± 2.95 mg/L, of which 42.6% (43/101) reached the therapeutic range. Among 35 cases of the first TDM, the proportion of which reached therapeutic range in the MFDS recommended dosing group was 50.0%, and in the MFDS non-compliant group was 21.7% (p=0.130). Among 34 cases initially out of therapeutic range, the dose adjusted group was more effective reaching the therapeutic range than the dose non-adjustment group (64.7% vs. 17.6%, p=0.005). Conclusion : This study confirmed that when administrating voriconazole to pediatric patients, dose adjustment through the TDM is necessary because it significantly increases the rate of Ctrough within the therapeutic range.
Abstract
Background : Voriconazole is the first-line treatment for invasive fungal infections, and therapeutic drug monitoring (TDM) is recommended because of its non-linear pharmacokinetic properties. Voriconazole was first approved for adults age 18 and older, which was subsequently approved for children with a maintenance dose of 7 mg/kg twice daily. However, dosing which is approved by the Korean Ministry of Food and Drug Safety (MFDS) was changed in 2013 to 9 mg/kg loading dose and 8 mg/kg maintenance dose, and the TDM criteria has not been validated for children. Thus, the purpose of this study was to confirm the effectiveness of the recommended dose by the MFDS and to contribute to establishing pediatric voriconazole dose guidelines by analyzing dose adjustment through the TDM. Methods : We retrospectively analyzed the TDM results of 32 children younger than age 18 who received voriconazole for the treatment of invasive fungal infection at Severance Hospital October 2016-June 2019. The therapeutic range of voriconazole was set to 1-5.5 mg/L. Results : A total of 32 patients were enrolled in this study and 101 TDM samples were collected (IV 52, PO 49). The mean of Ctrough was 2.43 ± 2.95 mg/L, of which 42.6% (43/101) reached the therapeutic range. Among 35 cases of the first TDM, the proportion of which reached therapeutic range in the MFDS recommended dosing group was 50.0%, and in the MFDS non-compliant group was 21.7% (p=0.130). Among 34 cases initially out of therapeutic range, the dose adjusted group was more effective reaching the therapeutic range than the dose non-adjustment group (64.7% vs. 17.6%, p=0.005). Conclusion : This study confirmed that when administrating voriconazole to pediatric patients, dose adjustment through the TDM is necessary because it significantly increases the rate of Ctrough within the therapeutic range.
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