Chan-Loi Yong, Joseph C Gathe, Gabriele Knecht, Catherine Orrell, Josep Mallolas, Daniel Podzamczer, Benoit Trottier, Wei Zhang, John P Sabo, Richard Vinisko, Murray Drulak, Anne-Marie Quinson
{"title":"奈韦拉平缓释400mg每日1次与奈韦拉平速释200mg每日2次在treatment-naïve HIV-1感染患者中的药代动力学分析","authors":"Chan-Loi Yong, Joseph C Gathe, Gabriele Knecht, Catherine Orrell, Josep Mallolas, Daniel Podzamczer, Benoit Trottier, Wei Zhang, John P Sabo, Richard Vinisko, Murray Drulak, Anne-Marie Quinson","doi":"10.1080/15284336.2017.1386811","DOIUrl":null,"url":null,"abstract":"<p><strong>Background: </strong>VERxVE data showed non-inferior virologic efficacy with extended release nevirapine (NVP-XR) dosed 400 mg once daily (QD) versus immediate release nevirapine (NVP-IR) 200 mg twice daily in a double-blind, non-inferiority study in treatment-naïve HIV-1-positive patients.</p><p><strong>Objective: </strong>To study the pharmacokinetics (PK) of the NVP formulations and identify possible associations with demographic factors.</p><p><strong>Methods: </strong>Patients with viral load ≥1000 copies/mL and CD4+ count > 50- <400 cells/mm<sup>3</sup> (males) and >50- <250 cells/mm<sup>3</sup> (females) at screening received NVP-IR 200 mg QD during a 14-day lead-in and were then stratified by baseline viral load and randomized to NVP-XR or -IR. NVP trough concentrations at steady state (SS) (C<sub>pre,ss,N</sub>) were measured up to week 48 for all participating patients. In a PK sub-study, SS parameters - AUC<sub>0-24</sub>, C<sub>max</sub>, C<sub>min</sub>, and peak-to-trough fluctuation were obtained and analyzed with relative bioavailability assessed at week 4 by plasma collection over 24 h.</p><p><strong>Results: </strong>Trough concentrations were stable from week 4 to week 48 for all patients (n = 1011) with both formulations, with NVP-XR/IR ratios of 0.77-0.82. Overall, 49 patients completed the PK sub-study: 24 XR and 25 IR. NVP-XR showed less peak-to-trough fluctuation (34.5%) than IR (55.2%), and lower AUC<sub>0-24</sub>, C<sub>min</sub>, C<sub>max</sub>, and trough concentrations than IR. However, no effect of SS trough concentrations was found on the virologic response proportion at least up to 1000 ng/mL. No significant association was found between NVP PK and gender, race, and viral load.</p><p><strong>Conclusion: </strong>These data suggest NVP-XR achieves lower but effective NVP exposure compared with NVP-IR.</p>","PeriodicalId":13216,"journal":{"name":"HIV Clinical Trials","volume":null,"pages":null},"PeriodicalIF":0.0000,"publicationDate":"2017-11-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://sci-hub-pdf.com/10.1080/15284336.2017.1386811","citationCount":"3","resultStr":"{\"title\":\"Pharmacokinetic analysis of nevirapine extended release 400 mg once daily vs nevirapine immediate release 200 mg twice daily formulation in treatment-naïve patients with HIV-1 infection.\",\"authors\":\"Chan-Loi Yong, Joseph C Gathe, Gabriele Knecht, Catherine Orrell, Josep Mallolas, Daniel Podzamczer, Benoit Trottier, Wei Zhang, John P Sabo, Richard Vinisko, Murray Drulak, Anne-Marie Quinson\",\"doi\":\"10.1080/15284336.2017.1386811\",\"DOIUrl\":null,\"url\":null,\"abstract\":\"<p><strong>Background: </strong>VERxVE data showed non-inferior virologic efficacy with extended release nevirapine (NVP-XR) dosed 400 mg once daily (QD) versus immediate release nevirapine (NVP-IR) 200 mg twice daily in a double-blind, non-inferiority study in treatment-naïve HIV-1-positive patients.</p><p><strong>Objective: </strong>To study the pharmacokinetics (PK) of the NVP formulations and identify possible associations with demographic factors.</p><p><strong>Methods: </strong>Patients with viral load ≥1000 copies/mL and CD4+ count > 50- <400 cells/mm<sup>3</sup> (males) and >50- <250 cells/mm<sup>3</sup> (females) at screening received NVP-IR 200 mg QD during a 14-day lead-in and were then stratified by baseline viral load and randomized to NVP-XR or -IR. NVP trough concentrations at steady state (SS) (C<sub>pre,ss,N</sub>) were measured up to week 48 for all participating patients. In a PK sub-study, SS parameters - AUC<sub>0-24</sub>, C<sub>max</sub>, C<sub>min</sub>, and peak-to-trough fluctuation were obtained and analyzed with relative bioavailability assessed at week 4 by plasma collection over 24 h.</p><p><strong>Results: </strong>Trough concentrations were stable from week 4 to week 48 for all patients (n = 1011) with both formulations, with NVP-XR/IR ratios of 0.77-0.82. Overall, 49 patients completed the PK sub-study: 24 XR and 25 IR. NVP-XR showed less peak-to-trough fluctuation (34.5%) than IR (55.2%), and lower AUC<sub>0-24</sub>, C<sub>min</sub>, C<sub>max</sub>, and trough concentrations than IR. However, no effect of SS trough concentrations was found on the virologic response proportion at least up to 1000 ng/mL. No significant association was found between NVP PK and gender, race, and viral load.</p><p><strong>Conclusion: </strong>These data suggest NVP-XR achieves lower but effective NVP exposure compared with NVP-IR.</p>\",\"PeriodicalId\":13216,\"journal\":{\"name\":\"HIV Clinical Trials\",\"volume\":null,\"pages\":null},\"PeriodicalIF\":0.0000,\"publicationDate\":\"2017-11-01\",\"publicationTypes\":\"Journal Article\",\"fieldsOfStudy\":null,\"isOpenAccess\":false,\"openAccessPdf\":\"https://sci-hub-pdf.com/10.1080/15284336.2017.1386811\",\"citationCount\":\"3\",\"resultStr\":null,\"platform\":\"Semanticscholar\",\"paperid\":null,\"PeriodicalName\":\"HIV Clinical Trials\",\"FirstCategoryId\":\"1085\",\"ListUrlMain\":\"https://doi.org/10.1080/15284336.2017.1386811\",\"RegionNum\":0,\"RegionCategory\":null,\"ArticlePicture\":[],\"TitleCN\":null,\"AbstractTextCN\":null,\"PMCID\":null,\"EPubDate\":\"\",\"PubModel\":\"\",\"JCR\":\"Q2\",\"JCRName\":\"Medicine\",\"Score\":null,\"Total\":0}","platform":"Semanticscholar","paperid":null,"PeriodicalName":"HIV Clinical Trials","FirstCategoryId":"1085","ListUrlMain":"https://doi.org/10.1080/15284336.2017.1386811","RegionNum":0,"RegionCategory":null,"ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":null,"EPubDate":"","PubModel":"","JCR":"Q2","JCRName":"Medicine","Score":null,"Total":0}
Pharmacokinetic analysis of nevirapine extended release 400 mg once daily vs nevirapine immediate release 200 mg twice daily formulation in treatment-naïve patients with HIV-1 infection.
Background: VERxVE data showed non-inferior virologic efficacy with extended release nevirapine (NVP-XR) dosed 400 mg once daily (QD) versus immediate release nevirapine (NVP-IR) 200 mg twice daily in a double-blind, non-inferiority study in treatment-naïve HIV-1-positive patients.
Objective: To study the pharmacokinetics (PK) of the NVP formulations and identify possible associations with demographic factors.
Methods: Patients with viral load ≥1000 copies/mL and CD4+ count > 50- <400 cells/mm3 (males) and >50- <250 cells/mm3 (females) at screening received NVP-IR 200 mg QD during a 14-day lead-in and were then stratified by baseline viral load and randomized to NVP-XR or -IR. NVP trough concentrations at steady state (SS) (Cpre,ss,N) were measured up to week 48 for all participating patients. In a PK sub-study, SS parameters - AUC0-24, Cmax, Cmin, and peak-to-trough fluctuation were obtained and analyzed with relative bioavailability assessed at week 4 by plasma collection over 24 h.
Results: Trough concentrations were stable from week 4 to week 48 for all patients (n = 1011) with both formulations, with NVP-XR/IR ratios of 0.77-0.82. Overall, 49 patients completed the PK sub-study: 24 XR and 25 IR. NVP-XR showed less peak-to-trough fluctuation (34.5%) than IR (55.2%), and lower AUC0-24, Cmin, Cmax, and trough concentrations than IR. However, no effect of SS trough concentrations was found on the virologic response proportion at least up to 1000 ng/mL. No significant association was found between NVP PK and gender, race, and viral load.
Conclusion: These data suggest NVP-XR achieves lower but effective NVP exposure compared with NVP-IR.
期刊介绍:
HIV Clinical Trials is devoted exclusively to presenting information on the latest developments in HIV/AIDS clinical research. This journal enables readers to obtain the most up-to-date, innovative research from around the world.