van Heeswijk R P, Veldkamp A I, Hoetelmans R M, Mulder J W, Schreij G, Hsu A, Lange J M, Beijnen J H, Meenhorst P L
Department of Pharmacy and Pharmacology, Slotervaart Hospital, Amsterdam, The Netherlands.
AIDS. 1999 Oct 1;13(14):F95-9. doi: 10.1097/00002030-199910010-00001.
To explore the steady-state plasma pharmacokinetics of indinavir in twice daily dosing regimens with and without the co-administration of 100 mg ritonavir.
Observational pharmacokinetic study.
HIV-1-infected individuals who use indinavir alone (1200 mg twice daily, n = 6), or the combination of 100 mg ritonavir twice daily plus either 800 mg (n = 6), or 1200 mg indinavir twice daily (n = 2).
Steady-state pharmacokinetics of indinavir and ritonavir were assessed by drawing 12 blood samples during an 8-h period after ingestion of the medication.
Significant differences were observed for indinavir pharmacokinetics between the dosing regimens indinavir 1200 mg twice daily alone and indinavir/ ritonavir 800/100 mg twice daily with respect to the mean trough concentration (0.21 and 0.99 microg/ml, respectively, P = 0.002), the mean maximum concentration (13.79 and 8.74 microg/ml, respectively, P = 0.028), and for the mean plasma elimination half-life (1.6 and 3.2 h, respectively, P = 0.001). The combination indinavir/ritonavir 1200/100 mg twice daily led to very high exposure to indinavir and was not well tolerated. However, the combination indinavir/ritonavir 800/100 mg twice daily was well tolerated and resulted in therapeutic concentrations of indinavir with improved trough concentrations and similar maximum concentrations as observed with the licensed dosage of 800 mg three times daily.
Combination of indinavir and 100 mg ritonavir in twice daily dosing regimens significantly affects the pharmacokinetic profile of indinavir. The results of this observational study provide a pharmacologic basis for the combination of indinavir (800 mg) and ritonavir (100 mg) in twice daily dosing regimens.
探讨茚地那韦在每日两次给药方案中，联合或不联合使用100mg利托那韦时的稳态血浆药代动力学。
观察性药代动力学研究。
单独使用茚地那韦（每日两次，每次1200mg，n = 6），或每日两次联合使用100mg利托那韦加800mg（n = 6）或每日两次1200mg茚地那韦（n = 2）的HIV-1感染个体。
在服药后8小时内采集12份血样，评估茚地那韦和利托那韦的稳态药代动力学。
茚地那韦每日两次单独服用1200mg与每日两次茚地那韦/利托那韦800/100mg给药方案相比，茚地那韦药代动力学在平均谷浓度（分别为0.21和0.99μg/ml，P = 0.002）、平均最大浓度（分别为13.79和8.74μg/ml，P = 0.028）以及平均血浆消除半衰期（分别为1.6和3.2小时，P = 0.001）方面存在显著差异。每日两次茚地那韦/利托那韦1200/100mg联合用药导致茚地那韦暴露量极高且耐受性不佳。然而，每日两次茚地那韦/利托那韦800/100mg联合用药耐受性良好，且茚地那韦达到治疗浓度，谷浓度有所改善，最大浓度与每日三次800mg的许可剂量相似。
茚地那韦与100mg利托那韦每日两次联合给药方案显著影响茚地那韦的药代动力学特征。本观察性研究结果为茚地那韦（800mg）和利托那韦（100mg）每日两次联合给药方案提供了药理学依据。
