Pharmacokinetics and 48 Week Efficacy of Low-dose Lopinavir/ritonavir in HIV-infected Children
Thanyawee Puthanakit, Jasper van der Lugt, Torsak Bunupuradah, Jintanat Ananworanich, Meena Gorowara, Chayapa Phasomsap, Thidarat Jupimai, Pitch Boonrak, Chitsanu Pancharoen, David Burger, Kiat Ruxrungtham
Department of Pediatrics, Faculty of Medicine, Chulalongkorn University, Bangkok, Thailand.Tel: þ66-2-255-7335; Fax: þ66-2-252-5779; E-mail: thanyawee.p@hivnat.org
บทคัดย่อ
Background: Lopinavir/ritonavir is a common protease inhibitor (PI) used for second-line regimens in  children. Several studies have shown higher plasma concentrations of antiretroviral agents in Thai adults than in Caucasians, suggesting that lower doses may be used.Methods: An open label study in 24 HIV-infected children between the age of 2 and 18 years, naive to PIs, randomized to receive either the WHO-recommended dose of lopinavir/ritonavir or a low dose (70% of the standard dose) twice daily in combination with zidovudine and lamivudine. A 12 h pharmacokinetic study was done at 4–6 weeks after starting treatment. Treatment outcomes were evaluated at week 48. The clinical trial number of the study is NCT00887120.Results: The medians [interquartile ranges (IQRs)] of age, body surface area, percentage CD4 and plasma HIV RNA were 9.5 years (7.0–12.3), 0.9 m2 (0.8–1.1), 17% (11%–24%) and 4.6 log10 copies/mL (4.1–4.9), respectively. The median (IQR) lopinavir dose was 279 mg/m2/dose (263–294) and 194 mg/m2/dose (176–206) in the standard and low-dose arms, respectively. Median (IQR) AUC0–12 and Ctrough of lopinavir were 117.6 mg.h/L (74.0–128.5) and 4.9 mg/L (2.7–8.0) for the standard arm and 83.8 mg.h/L (56.0–112.9) and 3.4 mg/L (2.7–5.4) for the low-dose arm. One child in the low-dose arm had a lopinavir pre-dose level of <1.0 mg/L. At week 48, the median percentage CD4 was 22%(15%–28%) and 27% (21%–31%) in the standard and low-dose arms, respectively, while 50% and 83% of children had HIV RNA <50 copies/mL, respectively (P=0.19).Conclusions: Low-dose lopinavir displayed adequate pharmacokinetic parameters and good efficacy as compared with standard-dose lopinavir in Thai children. A larger study to investigate the efficacy of low-dose lopinavir is warranted.
ที่มา
ปี 2552, November ปีที่: 64 ฉบับที่ 5 หน้า 1080-1086
คำสำคัญ
Protease inhibitors, Second-line treatment, Therapeutic drug monitoring