Teboho Mooko, Feziwe Busiswa Bisiwe, Enkosi Mondleki, Molefi Daniel Morobadi, Perpetual Chikobvu, Martin Munene Nyaga, Asis Bala, Dominique Goedhals, Thabiso Rafaki Petrus Mofokeng, Gabre Kemp, Kwazi Celani Zwakele Ndlovu
{"title":"腹膜透析液中检测到和检测不到 HIV-1 RNA 的终末期肾衰竭患者体内拉米夫定的稳态药代动力学。","authors":"Teboho Mooko, Feziwe Busiswa Bisiwe, Enkosi Mondleki, Molefi Daniel Morobadi, Perpetual Chikobvu, Martin Munene Nyaga, Asis Bala, Dominique Goedhals, Thabiso Rafaki Petrus Mofokeng, Gabre Kemp, Kwazi Celani Zwakele Ndlovu","doi":"10.1186/s40001-024-01972-8","DOIUrl":null,"url":null,"abstract":"<p><strong>Background: </strong>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.</p><p><strong>Methods: </strong>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.</p><p><strong>Results: </strong>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<sub>0-24 h</sub>, 651.3 ng/mL; 75 mg-AUC<sub>0-24 h</sub>, 677.84 ng/mL; 300 mg-AUC<sub>0-24 h</sub>, 3135.89 ng/mL) compared to CAPD effluents (50 mg-AUC<sub>0-24 h</sub>, 384.91 ng/mL; 75 mg-AUC<sub>0-24 h</sub>, 383.24 ng/mL; 300 mg-AUC<sub>0-24 h</sub>, 2001.60 ng/mL) among the entire study population. The C<sub>max</sub> (50 mg, 41.5 ng/mL; 75 mg, 53.2 ng/mL; 300 mg, 199.1 ng/mL) and C<sub>min</sub> (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.</p><p><strong>Conclusions: </strong>Steady-state lamivudine pharmacokinetic measures were variable among the entire study population. However, the total lamivudine exposure was within the therapeutic levels.</p>","PeriodicalId":11949,"journal":{"name":"European Journal of Medical Research","volume":null,"pages":null},"PeriodicalIF":2.8000,"publicationDate":"2024-07-18","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11256402/pdf/","citationCount":"0","resultStr":"{\"title\":\"Steady-state pharmacokinetics of lamivudine in end-stage kidney failure persons with detectable and undetectable HIV-1 RNA in peritoneal dialysis effluent.\",\"authors\":\"Teboho Mooko, Feziwe Busiswa Bisiwe, Enkosi Mondleki, Molefi Daniel Morobadi, Perpetual Chikobvu, Martin Munene Nyaga, Asis Bala, Dominique Goedhals, Thabiso Rafaki Petrus Mofokeng, Gabre Kemp, Kwazi Celani Zwakele Ndlovu\",\"doi\":\"10.1186/s40001-024-01972-8\",\"DOIUrl\":null,\"url\":null,\"abstract\":\"<p><strong>Background: </strong>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.</p><p><strong>Methods: </strong>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.</p><p><strong>Results: </strong>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<sub>0-24 h</sub>, 651.3 ng/mL; 75 mg-AUC<sub>0-24 h</sub>, 677.84 ng/mL; 300 mg-AUC<sub>0-24 h</sub>, 3135.89 ng/mL) compared to CAPD effluents (50 mg-AUC<sub>0-24 h</sub>, 384.91 ng/mL; 75 mg-AUC<sub>0-24 h</sub>, 383.24 ng/mL; 300 mg-AUC<sub>0-24 h</sub>, 2001.60 ng/mL) among the entire study population. The C<sub>max</sub> (50 mg, 41.5 ng/mL; 75 mg, 53.2 ng/mL; 300 mg, 199.1 ng/mL) and C<sub>min</sub> (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.</p><p><strong>Conclusions: </strong>Steady-state lamivudine pharmacokinetic measures were variable among the entire study population. However, the total lamivudine exposure was within the therapeutic levels.</p>\",\"PeriodicalId\":11949,\"journal\":{\"name\":\"European Journal of Medical Research\",\"volume\":null,\"pages\":null},\"PeriodicalIF\":2.8000,\"publicationDate\":\"2024-07-18\",\"publicationTypes\":\"Journal Article\",\"fieldsOfStudy\":null,\"isOpenAccess\":false,\"openAccessPdf\":\"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11256402/pdf/\",\"citationCount\":\"0\",\"resultStr\":null,\"platform\":\"Semanticscholar\",\"paperid\":null,\"PeriodicalName\":\"European Journal of Medical Research\",\"FirstCategoryId\":\"3\",\"ListUrlMain\":\"https://doi.org/10.1186/s40001-024-01972-8\",\"RegionNum\":3,\"RegionCategory\":\"医学\",\"ArticlePicture\":[],\"TitleCN\":null,\"AbstractTextCN\":null,\"PMCID\":null,\"EPubDate\":\"\",\"PubModel\":\"\",\"JCR\":\"Q2\",\"JCRName\":\"MEDICINE, RESEARCH & EXPERIMENTAL\",\"Score\":null,\"Total\":0}","platform":"Semanticscholar","paperid":null,"PeriodicalName":"European Journal of Medical Research","FirstCategoryId":"3","ListUrlMain":"https://doi.org/10.1186/s40001-024-01972-8","RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":null,"EPubDate":"","PubModel":"","JCR":"Q2","JCRName":"MEDICINE, RESEARCH & EXPERIMENTAL","Score":null,"Total":0}
Steady-state pharmacokinetics of lamivudine in end-stage kidney failure persons with detectable and undetectable HIV-1 RNA in peritoneal dialysis effluent.
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-AUC0-24 h, 651.3 ng/mL; 75 mg-AUC0-24 h, 677.84 ng/mL; 300 mg-AUC0-24 h, 3135.89 ng/mL) compared to CAPD effluents (50 mg-AUC0-24 h, 384.91 ng/mL; 75 mg-AUC0-24 h, 383.24 ng/mL; 300 mg-AUC0-24 h, 2001.60 ng/mL) among the entire study population. The Cmax (50 mg, 41.5 ng/mL; 75 mg, 53.2 ng/mL; 300 mg, 199.1 ng/mL) and Cmin (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.
期刊介绍:
European Journal of Medical Research publishes translational and clinical research of international interest across all medical disciplines, enabling clinicians and other researchers to learn about developments and innovations within these disciplines and across the boundaries between disciplines. The journal publishes high quality research and reviews and aims to ensure that the results of all well-conducted research are published, regardless of their outcome.