van der Lee Manon, Verweel Gwenda, de Groot Ronald, Burger David
Department of Clinical Pharmacy, Radboud University Nijmegen Medical Centre, Nijmegen, The Netherlands.
Antivir Ther. 2006;11(4):439-45.
Lopinavir is an HIV protease inhibitor that is co-formulated with ritonavir. The approved paediatric dose is 230/57.5 mg/m2 twice daily. Once-daily dosing may offer an advantage to adherence. We studied the pharmacokinetics of lopinavir/ritonavir in a once-daily regimen in HIV-1-infected children.
HIV-1-infected children on stable antiretroviral therapy with a viral load <50 copies/ml for at least 6 months received lopinavir/ritonavir 460/115mg/m2 once daily with zidovudine and lamivudine. Blood samples were collected at 0, 2, 4, 6, 8, 12, 18 and 24 h after observed intake during steady state. Target level for lopinavir Cmin was 1.0 mg/l, based on in vitro IC50 data.
Nineteen HIV-1-infected children with a median (range) age of 4.5 (1.4-12.9) years were enrolled. The median (interquartile range) dose of lopinavir was 456 (444-477) mg/m2. The mean (standard deviation) AUC0-24, Cmax and Cmin of lopinavir were 149.8 +/- 58.8 h*mg/l, 10.77 +/- 2.90 mg/l and 2.88 +/- 3.74 mg/l respectively. These values are comparable to data observed in adults using lopinavir/ritonavir 800/200 mg once daily. In 10/19 (53%) children Cmin was considered to be too low (<1.0 mg/l). Younger children more often experienced subtherapeutic trough levels.
Our findings indicate that 460/115 mg/m2 lopinavir/ritonavir once daily leads to mean pharmacokinetic parameters comparable to data of 800/200 mg lopinavir/ritonavir once daily in adults, although the variability observed in the trough levels is much higher in children. Further research, especially in young children, is necessary to determine whether a higher dosage of lopinavir/ritonavir once daily must be given to reach the target level for Cmin.
洛匹那韦是一种与利托那韦联合配方的HIV蛋白酶抑制剂。批准的儿科剂量为230/57.5mg/m²，每日两次。每日一次给药可能对依从性有好处。我们研究了HIV-1感染儿童每日一次用药方案中洛匹那韦/利托那韦的药代动力学。
接受稳定抗逆转录病毒治疗且病毒载量<50拷贝/ml至少6个月的HIV-1感染儿童，每日一次服用洛匹那韦/利托那韦460/115mg/m²，同时服用齐多夫定和拉米夫定。在稳态期间观察到服药后0、2、4、6、8、12、18和24小时采集血样。根据体外IC50数据，洛匹那韦Cmin的目标水平为1.0mg/l。
纳入了19名HIV-1感染儿童，中位（范围）年龄为4.5（1.4 - 12.9）岁。洛匹那韦的中位（四分位间距）剂量为456（444 - 477）mg/m²。洛匹那韦的平均（标准差）AUC0 - 24、Cmax和Cmin分别为149.8±58.8h*mg/l、10.77±2.90mg/l和2.88±3.74mg/l。这些值与成人每日一次服用800/200mg洛匹那韦/利托那韦时观察到的数据相当。在10/19（53%）的儿童中，Cmin被认为过低（<1.0mg/l）。年龄较小的儿童更常出现治疗不足的谷浓度。
我们的研究结果表明，每日一次服用460/115mg/m²洛匹那韦/利托那韦导致的平均药代动力学参数与成人每日一次服用800/200mg洛匹那韦/利托那韦的数据相当，尽管儿童中观察到的谷浓度变异性要高得多。有必要进一步研究，尤其是对年幼儿童，以确定是否必须给予更高剂量的洛匹那韦/利托那韦每日一次才能达到Cmin的目标水平。
