Pharmacokinetics and acceptability of once- versus twice-daily lamivudine and abacavir in HIV type-1-infected Ugandan children in the ARROW Trial.
BACKGROUND: No data on once-daily dosing of nucleoside analogues in African children currently exist. We compared the pharmacokinetics (PK) of once- versus twice-daily lamivudine and abacavir treatment using the World Health Organization recommended weight band dosing of scored adult tablets. METHO...
| Main Authors: | , , , , , , , , , , , , |
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| Format: | Journal article |
| Language: | English |
| Published: |
2010
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| _version_ | 1797099606867181568 |
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| author | Musiime, V Kendall, L Bakeera-Kitaka, S Snowden, W Odongo, F Thomason, M Musoke, P Adkison, K Burger, D Mugyenyi, P Kekitiinwa, A Gibb, D Walker, A |
| author_facet | Musiime, V Kendall, L Bakeera-Kitaka, S Snowden, W Odongo, F Thomason, M Musoke, P Adkison, K Burger, D Mugyenyi, P Kekitiinwa, A Gibb, D Walker, A |
| author_sort | Musiime, V |
| collection | OXFORD |
| description | BACKGROUND: No data on once-daily dosing of nucleoside analogues in African children currently exist. We compared the pharmacokinetics (PK) of once- versus twice-daily lamivudine and abacavir treatment using the World Health Organization recommended weight band dosing of scored adult tablets. METHODS: HIV type-1 (HIV-1)-infected Ugandan children aged 3-12 years receiving antiretroviral therapy that included lamivudine and abacavir twice daily (total 150+300 mg, 225+450 mg and 225/300+600 mg daily for 12-<20, 20-<25 and ≥25 kg, respectively) were enrolled in a crossover study. Plasma PK sampling (at 0, 1, 2, 4, 6, 8 and 12 h after observed morning intake) was performed for the twice-daily regimen at steady-state. Children were then switched to once-daily treatment with PK sampling repeated 4 weeks later (with an additional 24 h sample). Acceptability questionnaires were completed at both time points. Daily area under the curve (AUC(0-24)) and maximum concentrations (C(max)) were compared by geometric mean ratios (GMRs). RESULTS: A total of 41 HIV-1-infected children (median age of 7 years) and n=23, n=14 and n=4 in 12-<20, 20-<25 and ≥25 kg weight bands, respectively, were enrolled. Mean AUC(0-24) was 13.0 and 12.0 mg•h/l for once- and twice-daily lamivudine (GMR 1.09, 90% confidence intervals [CI] 0.98-1.20) and 15.3 and 15.6 mg•h/l for once- and twice-daily abacavir (GMR 0.98, 90% CI 0.89-1.08), respectively, with no difference in 3-6 versus 7-12 year olds. C(max) was 76% (lamivudine) and 64% (abacavir) higher on once-daily regimens. For both children and caregivers, once-daily dosing of lamivudine plus abacavir was highly acceptable and strongly preferred over twice-daily. CONCLUSIONS: In children aged 3-12 years, AUC(0-24) of lamivudine and abacavir were bioequivalent on once- and twice-daily regimens. Once-daily dosing of abacavir and lamivudine could provide an alternative dosing strategy for HIV-1-infected children, with high acceptability and strong preference suggesting the potential for improved adherence. |
| first_indexed | 2024-03-07T05:26:04Z |
| format | Journal article |
| id | oxford-uuid:e099551a-ae17-48e2-805d-3f9399ad8a27 |
| institution | University of Oxford |
| language | English |
| last_indexed | 2024-03-07T05:26:04Z |
| publishDate | 2010 |
| record_format | dspace |
| spelling | oxford-uuid:e099551a-ae17-48e2-805d-3f9399ad8a272022-03-27T09:48:27ZPharmacokinetics and acceptability of once- versus twice-daily lamivudine and abacavir in HIV type-1-infected Ugandan children in the ARROW Trial.Journal articlehttp://purl.org/coar/resource_type/c_dcae04bcuuid:e099551a-ae17-48e2-805d-3f9399ad8a27EnglishSymplectic Elements at Oxford2010Musiime, VKendall, LBakeera-Kitaka, SSnowden, WOdongo, FThomason, MMusoke, PAdkison, KBurger, DMugyenyi, PKekitiinwa, AGibb, DWalker, A BACKGROUND: No data on once-daily dosing of nucleoside analogues in African children currently exist. We compared the pharmacokinetics (PK) of once- versus twice-daily lamivudine and abacavir treatment using the World Health Organization recommended weight band dosing of scored adult tablets. METHODS: HIV type-1 (HIV-1)-infected Ugandan children aged 3-12 years receiving antiretroviral therapy that included lamivudine and abacavir twice daily (total 150+300 mg, 225+450 mg and 225/300+600 mg daily for 12-<20, 20-<25 and ≥25 kg, respectively) were enrolled in a crossover study. Plasma PK sampling (at 0, 1, 2, 4, 6, 8 and 12 h after observed morning intake) was performed for the twice-daily regimen at steady-state. Children were then switched to once-daily treatment with PK sampling repeated 4 weeks later (with an additional 24 h sample). Acceptability questionnaires were completed at both time points. Daily area under the curve (AUC(0-24)) and maximum concentrations (C(max)) were compared by geometric mean ratios (GMRs). RESULTS: A total of 41 HIV-1-infected children (median age of 7 years) and n=23, n=14 and n=4 in 12-<20, 20-<25 and ≥25 kg weight bands, respectively, were enrolled. Mean AUC(0-24) was 13.0 and 12.0 mg•h/l for once- and twice-daily lamivudine (GMR 1.09, 90% confidence intervals [CI] 0.98-1.20) and 15.3 and 15.6 mg•h/l for once- and twice-daily abacavir (GMR 0.98, 90% CI 0.89-1.08), respectively, with no difference in 3-6 versus 7-12 year olds. C(max) was 76% (lamivudine) and 64% (abacavir) higher on once-daily regimens. For both children and caregivers, once-daily dosing of lamivudine plus abacavir was highly acceptable and strongly preferred over twice-daily. CONCLUSIONS: In children aged 3-12 years, AUC(0-24) of lamivudine and abacavir were bioequivalent on once- and twice-daily regimens. Once-daily dosing of abacavir and lamivudine could provide an alternative dosing strategy for HIV-1-infected children, with high acceptability and strong preference suggesting the potential for improved adherence. |
| spellingShingle | Musiime, V Kendall, L Bakeera-Kitaka, S Snowden, W Odongo, F Thomason, M Musoke, P Adkison, K Burger, D Mugyenyi, P Kekitiinwa, A Gibb, D Walker, A Pharmacokinetics and acceptability of once- versus twice-daily lamivudine and abacavir in HIV type-1-infected Ugandan children in the ARROW Trial. |
| title | Pharmacokinetics and acceptability of once- versus twice-daily lamivudine and abacavir in HIV type-1-infected Ugandan children in the ARROW Trial. |
| title_full | Pharmacokinetics and acceptability of once- versus twice-daily lamivudine and abacavir in HIV type-1-infected Ugandan children in the ARROW Trial. |
| title_fullStr | Pharmacokinetics and acceptability of once- versus twice-daily lamivudine and abacavir in HIV type-1-infected Ugandan children in the ARROW Trial. |
| title_full_unstemmed | Pharmacokinetics and acceptability of once- versus twice-daily lamivudine and abacavir in HIV type-1-infected Ugandan children in the ARROW Trial. |
| title_short | Pharmacokinetics and acceptability of once- versus twice-daily lamivudine and abacavir in HIV type-1-infected Ugandan children in the ARROW Trial. |
| title_sort | pharmacokinetics and acceptability of once versus twice daily lamivudine and abacavir in hiv type 1 infected ugandan children in the arrow trial |
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