Kovacs Andrea, Cowles Mary Kathryn, Britto Paula, Capparelli Edmund, Fowler Mary Glenn, Moye Jack, McIntosh Ken, Rathore Mobeen H, Pitt Jane, Husson Robert N
Maternal, Child and Adolescent Center for Infectious Diseases and Virology, University of Southern California, Keck School of Medicine, Los Angeles, 90033, USA.
Pediatr Infect Dis J. 2005 Jun;24(6):503-9. doi: 10.1097/01.inf.0000164787.63237.0b.
There are limited numbers of drugs that are available in formulations that are appropriate for neonates and few studies assessing resistance among infants born to human immunodeficiency virus (HIV)-infected women.
Pharmacokinetics and tolerance of didanosine (ddI) were determined for infants < or =120 days of age. Infants received at least 24 hours of zidovudine (ZDV) treatment, followed by a single ddI dose and pharmacokinetic sampling. The target area under the concentration-time curve (AUC) was between 2.5 and 5.0 microM . hour. Toxicity and drug resistance mutations were assessed at baseline and follow-up times.
The initial ddI pharmacokinetic dosing of 50 mg/m for infants >28 days of age achieved a median AUC0-infinity of 2.8 microM . hour. For infants < or =28 days of age, the target AUC was achieved after dose escalation from 25 mg/m (median AUC0-infinity, 1.4 microM . hour) to 50 mg/m (median AUC0-infinity, 5.40 microM . hour). At baseline, 25% of infected infants had drug resistance mutations (9 of 44 to ZDV and 2 of 44 to ddI). Resistance mutations were present for 29% of infants (5 of 17 infants) with in utero ZDV exposure and 25% (8 of 32 infants) with prior ZDV treatment. The most common ZDV mutation noted at baseline was the T215Y/F (n = 7) mutation; 2 of these infants also had the M41L mutation, which is associated with high level ZDV resistance. No prior exposure was noted for the 2 infants with ddI resistance, which indicates possible perinatal transmission of ddI-resistant virus to these infants.
A dose of 50 mg/m is the appropriate ddI dose for infants <120 days of age and is a safe treatment for newborns when used in combination with ZDV. Genotypic resistance occurs frequently among infected infants exposed to ZDV during gestation or postnatally, which suggests that resistance testing should be considered for infants with newly diagnosed HIV infection.
适用于新生儿的药物制剂数量有限，且评估感染人类免疫缺陷病毒（HIV）的女性所生婴儿耐药性的研究较少。
确定年龄小于或等于120天的婴儿中去羟肌苷（ddI）的药代动力学和耐受性。婴儿接受至少24小时的齐多夫定（ZDV）治疗，随后给予单次ddI剂量并进行药代动力学采样。浓度-时间曲线下的目标面积（AUC）在2.5至5.0微摩尔·小时之间。在基线和随访时评估毒性和耐药性突变。
年龄大于28天的婴儿初始ddI药代动力学剂量为50毫克/平方米，中位AUC0-无穷大为2.8微摩尔·小时。对于年龄小于或等于28天的婴儿，在剂量从25毫克/平方米（中位AUC0-无穷大，1.4微摩尔·小时）逐步增加到50毫克/平方米（中位AUC0-无穷大，5.40微摩尔·小时）后达到目标AUC。在基线时，25%的感染婴儿有耐药性突变（对ZDV为44例中的9例，对ddI为44例中的2例）。宫内暴露于ZDV的婴儿中有29%（17例婴儿中的5例）和先前接受ZDV治疗的婴儿中有25%（32例婴儿中的8例）存在耐药性突变。基线时最常见的ZDV突变是T215Y/F（n = 7）突变；其中2例婴儿也有M41L突变，这与高水平的ZDV耐药性相关。2例对ddI耐药的婴儿未发现先前暴露，这表明耐药的ddI病毒可能在围产期传播给这些婴儿。
50毫克/平方米的剂量是年龄小于120天婴儿的合适ddI剂量，与ZDV联合使用时对新生儿是一种安全的治疗方法。在孕期或出生后暴露于ZDV的感染婴儿中，基因型耐药性频繁出现，这表明对于新诊断为HIV感染的婴儿应考虑进行耐药性检测。
