Dose optimisation of voriconazole with therapeutic drug monitoring in children: a single-centre experience in China.
The pharmacokinetic profile of voriconazole is highly variable, rendering inconsistent and/or inadequate dosing, especially in children <2 years old. A retrospective analysis was performed in children receiving voriconazole with at least one plasma trough level (Ctrough) monitored. Statistical analyses were performed to examine the dose-exposure relationship as well as other factors potentially affecting voriconazole Ctroughin children of different ages. A total of 107 paediatric patients were included, of whom 75 were <2 years old. The voriconazole Ctroughwas highly variable in patients aged <2 years and those aged 2-12 years. Only 47.7% of children reached the therapeutic target of 1.0-5.5 mg/L at initial dosing, whereas 48.6% of Ctroughvalues were subtherapeutic and 3.7% were supratherapeutic. The mean maintenance dose to reach an adequate Ctroughwas 5.9 mg/kg compared with 5.1 mg/kg, resulting in insufficient levels (P = 0.005) in children aged <2 years. In this age group, the 5 to <7 mg/kg dose range significantly increased the chance of reaching the therapeutic target compared with the 3 to <5 mg/kg dose range (56.7% vs. 25.8%; P = 0.014). Overall, factors such as sex, age, liver function, renal function and co-administered medications explained only 15.9% of variability in voriconazole exposure. Co-administration of omeprazole significantly increased the voriconazole level (P = 0.032), likely through CYP2C19 inhibition. This is the largest series to date describing voriconazole dose-exposure relationships in children aged <2 years. A starting maintenance dose of 5 to <7 mg/kg intravenously twice daily may be required for most children of Asian origin to reach the therapeutic target.
Department of Pharmacy, Tongji Hospital of Tongji Medical College, Huazhong University of Science & Technology, 13 Hangkong Road, Wuhan, Hubei 430030, China.
Liang
L
Liu
School of Pharmacy, Huazhong University of Science & Technology, Wuhan, China.
Xing
X
Zhou
Department of Pediatrics, Tongji Hospital of Tongji Medical College, Huazhong University of Science & Technology, Wuhan, China.
Tingting
T
Wu
School of Pharmacy, Huazhong University of Science & Technology, Wuhan, China.
Hongliang
H
Jiang
Department of Pharmacy, Tongji Hospital of Tongji Medical College, Huazhong University of Science & Technology, 13 Hangkong Road, Wuhan, Hubei 430030, China.
Sitao
S
Yang
Department of Pharmacy, Tongji Hospital of Tongji Medical College, Huazhong University of Science & Technology, 13 Hangkong Road, Wuhan, Hubei 430030, China. Electronic address: zhangyang_jhl@163.com.
Yang
Y
Zhang
D000935:Antifungal Agents / Q000008:administration & dosage* / Q000493:pharmacokinetics*; D002648:Child; D002675:Child, Preschool; D002681:China; D004347:Drug Interactions; D016903:Drug Monitoring; D005260:Female; D006801:Humans; D007223:Infant; D007231:Infant, Newborn; D008297:Male; D009853:Omeprazole / Q000008:administration & dosage; D010949:Plasma / Q000737:chemistry; D054328:Proton Pump Inhibitors / Q000008:administration & dosage; D012189:Retrospective Studies; D065819:Voriconazole / Q000008:administration & dosage* / Q000493:pharmacokinetics*
D000935:Antifungal Agents; D054328:Proton Pump Inhibitors; D065819:Voriconazole; D009853:Omeprazole
Children; Omeprazole; Therapeutic drug monitoring; Voriconazole