Faulds D, Brogden R N
Adis International Limited, Auckland, New Zealand.
Drugs. 1992 Jul;44(1):94-116. doi: 10.2165/00003495-199244010-00008.
Didanosine is a dideoxynucleoside analogue which undergoes intracellular conversion to the putative active triphosphate metabolite. The active metabolite appears to inhibit viral reverse transcriptase and terminate the proviral DNA, and produces virustatic inhibition of actively replicating human immunodeficiency virus (HIV) at clinically relevant concentrations. In phase I studies didanosine had beneficial effects on various surrogate markers of clinical efficacy and also improved clinical manifestations of HIV infection, with a 21-month survival rate of 80% in patients with acquired immune deficiency syndrome (AIDS) and 93% in patients with AIDS-related complex (ARC) in 1 study. Didanosine also improved CD4+ cell counts in a phase II/III trial in patients previously treated with zidovudine, whereas cell counts declined in patients continuing zidovudine therapy. However, the effects of didanosine on clinical end-points (disease progression, survival, HIV encephalopathy) remain to be established. Peripheral neuropathy and pancreatitis are the predominant dose-limiting adverse events and didanosine therapy should be withdrawn in patients developing signs or symptoms of pancreatitis and during acute treatment of Pneumocystis carinii pneumonia. However, at currently recommended clinical dosages didanosine is generally well tolerated with minimal haematological toxicity. Thus, in a therapeutic area with few treatment options, didanosine offers a welcome alternative for patients intolerant of, or resistant to, zidovudine. There are a number of clinical trials in progress evaluating didanosine alone or in combination with other antiviral agents, and these results are awaited with considerable interest.
去羟肌苷是一种双脱氧核苷类似物，在细胞内转化为假定的活性三磷酸代谢产物。活性代谢产物似乎能抑制病毒逆转录酶并终止前病毒DNA，在临床相关浓度下对活跃复制的人类免疫缺陷病毒（HIV）产生病毒生长抑制作用。在I期研究中，去羟肌苷对各种临床疗效替代指标有有益影响，还改善了HIV感染的临床表现，在1项研究中，获得性免疫缺陷综合征（AIDS）患者的21个月生存率为80%，艾滋病相关综合征（ARC）患者为93%。在一项II/III期试验中，去羟肌苷还使先前接受齐多夫定治疗的患者的CD4+细胞计数增加，而继续接受齐多夫定治疗的患者细胞计数下降。然而，去羟肌苷对临床终点（疾病进展、生存率、HIV脑病）的影响仍有待确定。周围神经病变和胰腺炎是主要的剂量限制性不良事件，出现胰腺炎体征或症状的患者以及在卡氏肺孢子虫肺炎急性治疗期间应停用去羟肌苷治疗。然而，按照目前推荐的临床剂量，去羟肌苷一般耐受性良好，血液学毒性极小。因此，在治疗选择较少的治疗领域，去羟肌苷为对齐多夫定不耐受或耐药的患者提供了一种受欢迎的替代药物。目前有多项正在进行的临床试验评估去羟肌苷单独使用或与其他抗病毒药物联合使用的情况，人们对这些结果拭目以待。
