E measured 24-h darunavir Ctrough,ss with the same regimen reported
E measured 24-h darunavir Ctrough,ss with the same regimen reported by Gutierrez-Valencia et al [24]. The maximum observed darunavir level at 2 weeks was 5840 ng/mL (median), range 3590?840 ng/mL (n = 9), and was reached at a median of 2.5 h (range 1? h) after dosing. This is generally similar to published data for 60 subjects receiving darunavir 800 mg/cobicistat 150 mg with two nucleoside/nucleotide reverse transcriptaseHarris et al. AIDS Res Ther (2017) 14:Page 6 ofTable 3 Plasma concentrations of darunavir and AZD3759 cost elvitegravir at 24 h post-doseStudy intervention N Darunavir Ctrough,ss, ng/mL Median/mean DRV/rtv, pre-switch E/C/F/TDF + DRV DRV/rtv 800/100 mg DRV/cobi 800/150 PubMed ID:https://www.ncbi.nlm.nih.gov/pubmed/29045898 mg 5 9 335a 119 298a 59 32 E/C/F/TDF (no DRV) E/C/F/TDF + DRV E/C/F/TAF + DRV 419 32 24 8aElvitegravir Ctrough,ss, ng/mL Median/mean ??184 (median) 200 (mean) ?????451 (mean) 250 (mean) 234 (mean) ?464 (mean) Range ?< 80?35 ?????58?341 30?62 92?32 ?NARefs.Range 667?150 96?48 368?242 IQR 1470?460 SD 1320 SD 969 288?641 ??163?641 164?01 (IQR)b NA981 (median) 932 (mean) 482 (median) 490 (mean) 2041 (median) 1820 (mean) 2150 (mean) 1311 (mean) 1319 (mean) ??1294 (mean) 273 PubMed ID:https://www.ncbi.nlm.nih.gov/pubmed/27607577 (median)b 1250 (mean)[22] [23] [25] [25] [24] [26] [24] [24] [12] [36]Ctrough,ss trough plasma concentration at steady-state, DRV darunavir, rtv ritonavir, cobi cobicistat, E/C/F/TDF elvitegravir/cobicistat/emtricitabine/tenofovir disproxil fumarate, E/C/F/TAF elvitegravir/cobicistat/ emtricitabine/ tenofovir alafenamide, IQR interquartile range, SD standard deviation, NA not availableaPopulation pharmacokinetic estimate; b estimatedinhibitors: mean darunavir Cmax 7663 ng/mL (standard deviation 1920), median tmax 3.5 h (interquartile range [IQR] 2.5?.3 h) [25].Elvitegravir and cobicistat levelsnucleotide reverse transcriptase inhibitors, mean cobicistat C0h was 76 ng/mL (standard deviation 186), mean Cmax was 991 ng/mL (standard deviation 331), and median tmax was 3.5 h (IQR 2.0?.5) [25].Among the 9 subjects who had drug levels measured 2 weeks after switching to E/C/F/TDF and darunavir, the median elvitegravir Ctrough,ss was 184 ng/mL (range < 80?96). Mean and median elvitegravir Ctrough,ss are shown in Table 3 for the purpose of comparison with data from the literature. Our observed elvitegravir Ctrough,ss were somewhat lower than the manufacturer's population pharmacokinetic estimates for E/C/F/TDF without darunavir [26], but generally similar to 24-h Ctrough,ss measured by Gutierrez-Valencia et al. among patients taking E/C/F/ TDF either with or without darunavir [24]. The maximum observed elvitegravir level was 1230 ng/ mL (median), range 651?400 ng/mL (n = 9), and was reached at a median of 3 h (range 1? h) after dosing. In comparison, population PK data for E/C/F/TDF (n = 419) provide a mean Cmax of 1731 ng/mL (standard deviation 23) with a tmax of 4.0 h [6, 26]. Cobicistat levels at 24 h post-dosing were < 50 ng/mL in all 9 of our study subjects with available drug levels. The maximum observed cobicistat level was 769 ng/ mL (median), range 493?090 ng/mL (n = 9), and was reached at a median of 2 h (range 2? h) after dosing. In published data for 60 subjects receiving darunavir 800 mg/cobicistat 150 mg with two nucleoside/Discussion Among 10 treatment-experienced HIV-infected patients who had viral load consistently < 200 copies/mL on a multiple-class antiretroviral regimen, a switch to a twopill once-daily regimen of E/C/F/TDF and darunavir was safe and effective in maint.
