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. Issue 5 (2nd November 2017)

• Record Type: Journal Article
• Authors: Yong, Chan-Loi; Gathe, Joseph C.; Knecht, Gabriele; Orrell, Catherine; Mallolas, Josep; Podzamczer, Daniel; Trottier, Benoit; Zhang, Wei; Sabo, John P.; Vinisko, Richard; Drulak, Murray; Quinson, Anne-Marie
• Is Part Of: HIV clinical trials. Volume 18:Issue 5/6(2017)
• Page Start: 189
• Page End: 195
• Publication Date: 2017-11-02
• Subjects: Nevirapine -- Extended release -- Immediate release -- HIV -- Pharmacokinetic -- Virologic efficacy -- Bioavailability; HIV Infections -- Chemotherapy -- Periodicals; AIDS (Disease) -- Chemotherapy -- Periodicals; HIV Infections -- Research -- Periodicals; AIDS (Disease) -- Research -- Periodicals; 616.979206105
• DOI: 10.1080/15284336.2017.1386811
• Languages: English
• ISSNs: 1528-4336

Abstract

Abstract : 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/mm 3 (males) and >50– <250 cells/mm 3 (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 pre, ss, N ) were measured up to week 48 for all participating patients. In a PK sub-study, SS parameters – AUC0–24, C max, C min, 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, C min, C max, 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.