Cato A, Qian J, Hsu A, Vomvouras S, Piergies A A, Leonard J, Granneman R
Pharmaceutical Products Division, Abbott Laboratories, Abbott Park, Illinois, USA.
J Acquir Immune Defic Syndr Hum Retrovirol. 1998 Aug 15;18(5):466-72. doi: 10.1097/00042560-199808150-00008.
The effect of coadministration of ritonavir and didanosine (ddI) on the pharmacokinetics of these drugs was investigated in a single-center, three-period, crossover study. Eighteen asymptomatic, HIV-positive men were assigned randomly to 6 different sequences of 3 regimens: ddI (200 mg every 12 hours) alone for 4 days, ritonavir (600 mg every 12 hours) alone for 4 days, and 4 days of ddI with ritonavir under dose-staggering conditions. Although not statistically significant, ritonavir concentrations were slightly higher on average (<10%) with concurrent administration of ddI compared with those of ritonavir alone. In contrast, ddI concentrations were lower with concurrent administration compared with those of ddI alone; maximum concentration and area under the concentration-time curve were reduced by about 15% (p < .05). The ddI elimination rate constant was unaffected by ritonavir, suggesting no change in ddI's systemic metabolism. Adverse events were similar between regimens. The relatively minor changes in ritonavir and ddI pharmacokinetics are probably not clinically relevant; therefore, dosage adjustment of either compound appears unnecessary when administered concurrently. However, the combination regimen of ddI and ritonavir continue to be evaluated clinically.
在一项单中心、三阶段、交叉研究中，研究了利托那韦与去羟肌苷（ddI）联合给药对这些药物药代动力学的影响。18名无症状的HIV阳性男性被随机分配到3种治疗方案的6种不同序列中：单独使用ddI（每12小时200毫克）4天，单独使用利托那韦（每12小时600毫克）4天，以及在剂量交错条件下ddI与利托那韦联合使用4天。虽然无统计学意义，但与单独使用利托那韦相比，同时给予ddI时利托那韦浓度平均略高（<10%）。相反，与单独使用ddI相比，同时给药时ddI浓度较低；最大浓度和浓度-时间曲线下面积降低约15%（p<0.05）。ddI消除速率常数不受利托那韦影响，表明ddI的全身代谢无变化。各治疗方案之间不良事件相似。利托那韦和ddI药代动力学的相对微小变化可能与临床无关；因此，同时给药时两种化合物似乎无需调整剂量。然而，ddI与利托那韦的联合治疗方案仍在进行临床评估。
