Steady-state pharmacokinetics of lamivudine in end-stage kidney failure persons with detectable and undetectable HIV-1 RNA in peritoneal dialysis effluent.

Autor: Mooko T; Department of Internal Medicine (G73), University of the Free State, PO Box 339, Bloemfontein, 9300, South Africa. 2011018955@ufs4life.ac.za.; Next Generation Sequencing Unit and Division of Virology, University of the Free State, Bloemfontein, South Africa. 2011018955@ufs4life.ac.za., Bisiwe FB; Department of Internal Medicine (G73), University of the Free State, PO Box 339, Bloemfontein, 9300, South Africa.; Division of Nephrology, University of the Free State, Bloemfontein, South Africa., Mondleki E; Department of Pharmacology, University of the Free State, Bloemfontein, South Africa., Morobadi MD; Division of Virology, University of the Free State, Bloemfontein, South Africa.; Ampath Laboratories, Pretoria, South Africa., Chikobvu P; Department of Health of the Free State, Bloemfontein, South Africa.; Department of Community Health, University of the Free State, Bloemfontein, South Africa., Nyaga MM; Next Generation Sequencing Unit and Division of Virology, University of the Free State, Bloemfontein, South Africa., Bala A; Pharmacology and Drug Discovery Research Laboratory, Division of Life Sciences, Institute of Advanced Study in Science and Technology (IASST), Vigyan Path, Guwahati, Assam, 781035, India., Goedhals D; Division of Virology, University of the Free State, Bloemfontein, South Africa.; PathCare Vermaak, Pretoria, South Africa., Mofokeng TRP; Department of Internal Medicine (G73), University of the Free State, PO Box 339, Bloemfontein, 9300, South Africa.; Department of Health of the Free State, Bloemfontein, South Africa., Kemp G; Department of Microbiology and Biochemistry, University of the Free State, Bloemfontein, South Africa., Ndlovu KCZ; Kidney and Hypertension Research Unit and Division of Nephrology and Hypertension, University of Cape Town, Cape Town, South Africa.
Jazyk: angličtina
Zdroj: European journal of medical research [Eur J Med Res] 2024 Jul 18; Vol. 29 (1), pp. 374. Date of Electronic Publication: 2024 Jul 18.
DOI: 10.1186/s40001-024-01972-8
Abstrakt: Background: Renally adjusted lamivudine dosages are effective. However, some of the kidney failure patients managed with lamivudine-containing regimens are failing to suppress HIV in peritoneal dialysis (CAPD) effluent. The steady-state lamivudine pharmacokinetics among these patients was evaluated.
Methods: This overnight open-label pharmacokinetic study enrolled participants living with HIV and managed with CAPD. Lamivudine levels in blood serum and CAPD effluent samples were quantified using liquid chromatography coupled with a mass spectrometer. Pharmacokinetic measures were obtained through non-compartmental analysis.
Results: Twenty-eight participants were recruited with a median antiretroviral (ARV) drug duration of 8 (IQR,4.5-10.5) years and a CAPD duration of 13.3 (IQR,3.3-31.9) months. 14.3% (4/28) had detectable unsuppressed HIV-1 viral load in CAPD effluents. The majority (78,6%,22/28) of participants received a 50 mg dose, while 10.7% (3/28), and another 10.7% (3/28) received 75 mg and 300 mg dosages, respectively. Among those treated with 75 and 300 mg, 66.7% (2/3) and 33.3% (1/3) had detectable HIV-VL in CAPD, respectively. The peritoneal membrane characteristics and CAPD system strengths were variable across the entire study population. Lamivudine exposure was increased in blood serum (50 mg-AUC 0-24 h , 651.3 ng/mL; 75 mg-AUC 0-24 h , 677.84 ng/mL; 300 mg-AUC 0-24 h , 3135.89 ng/mL) compared to CAPD effluents (50 mg-AUC 0-24 h , 384.91 ng/mL; 75 mg-AUC 0-24 h , 383.24 ng/mL; 300 mg-AUC 0-24 h , 2001.60 ng/mL) among the entire study population. The C max (50 mg, 41.5 ng/mL; 75 mg, 53.2 ng/mL; 300 mg, 199.1 ng/mL) and C min (50 mg, 17.8 ng/mL; 75 mg, 16.4 ng/mL; 300 mg, 76.4 ng/mL) measured in serum were within the therapeutic levels.
Conclusions: Steady-state lamivudine pharmacokinetic measures were variable among the entire study population. However, the total lamivudine exposure was within the therapeutic levels.
(© 2024. The Author(s).)
Databáze: MEDLINE
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