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Pharmacokinetics of emtricitabine, didanosine and efavirenz administered once‐daily for the treatment of HIV‐infected adults (pharmacokinetic substudy of the ANRS 091 trial) *
Author(s) -
Molina JM,
Peytavin G,
Perusat S,
LascouxCombes C,
Sereni D,
Rozenbaum W,
Chene G
Publication year - 2004
Publication title -
hiv medicine
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.53
H-Index - 79
eISSN - 1468-1293
pISSN - 1464-2662
DOI - 10.1111/j.1468-1293.2004.00194.x
Subject(s) - cmin , cmax , pharmacokinetics , efavirenz , emtricitabine , medicine , pharmacology , didanosine , area under the curve , human immunodeficiency virus (hiv) , antiretroviral therapy , viral load , virology
Objective This study was conducted to investigate the pharmacokinetics of emtricitabine (FTC), didanosine (ddI), and efavirenz (EFV) when administered in a once‐daily combination. Methods Nine antiretroviral‐naïve HIV‐infected adults who received FTC [200 mg once a day (qd)], ddI (400 mg qd if ≥60 kg; 250 mg qd if <60 kg) and EFV (600 mg qd) were studied. The following pharmacokinetic (PK) parameters were determined over 24 h at steady‐state after 4 weeks of treatment: area under the plasma concentration vs. time curve (AUC 0–24 h ), maximum ( C max ) and minimum ( C min ) plasma concentrations, time to reach C max ( T max ), and the elimination half‐life ( t 1/2 ). EFV plasma concentrations were also measured during follow‐up. Results Median PK parameters for FTC, ddI and EFV, respectively, were as follows. AUC 0–24 h : 7.2, 7.0 and 36.4 h×mg/L; C max : 1.8, 2.6 and 2.5 mg/L; C min : 0.04, < 0.01 and 1.0 mg/L; T max : 1.8, 1.1 and 2.5 h; t 1/2 : 7.4, 2.3, and 23.7 h. EFV plasma concentrations measured 10–13 h postdosing were higher during follow‐up than during the PK study (2.57 vs. 1.19 mg/L, P <0.01). Conclusion The simultaneous administration of FTC, ddI and EFV did not affect the PK parameters of FTC when compared to historical controls. EFV C max and C min were lower than expected, but the data may have been slightly underestimated in this study. High ddI AUC and C max were measured in these patients, and further studies are warranted to confirm this finding.