Abacavir pharmacokinetics in African children living with HIV : A pooled analysis describing the effects of age, malnutrition and common concomitant medications
© 2021 The Authors. British Journal of Clinical Pharmacology published by John Wiley & Sons Ltd on behalf of British Pharmacological Society..
AIMS: Abacavir is part of WHO-recommended regimens to treat HIV in children under 15 years of age. In a pooled analysis across four studies, we describe abacavir population pharmacokinetics to investigate the influence of age, concomitant medications, malnutrition and formulation.
METHODS: A total of 230 HIV-infected African children were included, with median (range) age of 2.1 (0.1-12.8) years and weight of 9.8 (2.5-30.0) kg. The population pharmacokinetics of abacavir was described using nonlinear mixed-effects modelling.
RESULTS: Abacavir pharmacokinetics was best described by a two-compartment model with first-order elimination, and absorption described by transit compartments. Clearance was predicted around 54% of its mature value at birth and 90% at 10 months. The estimated typical clearance at steady state was 10.7 L/h in a child weighing 9.8 kg co-treated with lopinavir/ritonavir, and was 12% higher in children receiving efavirenz. During coadministration of rifampicin-based antituberculosis treatment and super-boosted lopinavir in a 1:1 ratio with ritonavir, abacavir exposure decreased by 29.4%. Malnourished children living with HIV had higher abacavir exposure initially, but this effect waned with nutritional rehabilitation. An additional 18.4% reduction in clearance after the first abacavir dose was described, suggesting induction of clearance with time on lopinavir/ritonavir-based therapy. Finally, absorption of the fixed dose combination tablet was 24% slower than the abacavir liquid formulation.
CONCLUSION: In this pooled analysis we found that children on lopinavir/ritonavir or efavirenz had similar abacavir exposures, while concomitant TB treatment and super-boosted lopinavir gave significantly reduced abacavir concentrations.
| Medienart: |
E-Artikel |
|---|
| Erscheinungsjahr: |
2022 |
|---|---|
| Erschienen: |
2022 |
| Enthalten in: |
Zur Gesamtaufnahme - volume:88 |
|---|---|
| Enthalten in: |
British journal of clinical pharmacology - 88(2022), 2 vom: 15. Feb., Seite 403-415 |
| Sprache: |
Englisch |
|---|
| Beteiligte Personen: |
Tikiso, Tjokosela [VerfasserIn] |
|---|
| Links: |
|---|
| Anmerkungen: |
Date Completed 11.04.2022 Date Revised 05.10.2022 published: Print-Electronic Citation Status MEDLINE |
|---|
| doi: |
10.1111/bcp.14984 |
|---|
| funding: |
|
|---|---|
| Förderinstitution / Projekttitel: |
|
| PPN (Katalog-ID): |
NLM328056618 |
|---|
| LEADER | 01000naa a22002652 4500 | ||
|---|---|---|---|
| 001 | NLM328056618 | ||
| 003 | DE-627 | ||
| 005 | 20231225202136.0 | ||
| 007 | cr uuu---uuuuu | ||
| 008 | 231225s2022 xx |||||o 00| ||eng c | ||
| 024 | 7 | |a 10.1111/bcp.14984 |2 doi | |
| 028 | 5 | 2 | |a pubmed24n1093.xml |
| 035 | |a (DE-627)NLM328056618 | ||
| 035 | |a (NLM)34260082 | ||
| 040 | |a DE-627 |b ger |c DE-627 |e rakwb | ||
| 041 | |a eng | ||
| 100 | 1 | |a Tikiso, Tjokosela |e verfasserin |4 aut | |
| 245 | 1 | 0 | |a Abacavir pharmacokinetics in African children living with HIV |b A pooled analysis describing the effects of age, malnutrition and common concomitant medications |
| 264 | 1 | |c 2022 | |
| 336 | |a Text |b txt |2 rdacontent | ||
| 337 | |a ƒaComputermedien |b c |2 rdamedia | ||
| 338 | |a ƒa Online-Ressource |b cr |2 rdacarrier | ||
| 500 | |a Date Completed 11.04.2022 | ||
| 500 | |a Date Revised 05.10.2022 | ||
| 500 | |a published: Print-Electronic | ||
| 500 | |a Citation Status MEDLINE | ||
| 520 | |a © 2021 The Authors. British Journal of Clinical Pharmacology published by John Wiley & Sons Ltd on behalf of British Pharmacological Society. | ||
| 520 | |a AIMS: Abacavir is part of WHO-recommended regimens to treat HIV in children under 15 years of age. In a pooled analysis across four studies, we describe abacavir population pharmacokinetics to investigate the influence of age, concomitant medications, malnutrition and formulation | ||
| 520 | |a METHODS: A total of 230 HIV-infected African children were included, with median (range) age of 2.1 (0.1-12.8) years and weight of 9.8 (2.5-30.0) kg. The population pharmacokinetics of abacavir was described using nonlinear mixed-effects modelling | ||
| 520 | |a RESULTS: Abacavir pharmacokinetics was best described by a two-compartment model with first-order elimination, and absorption described by transit compartments. Clearance was predicted around 54% of its mature value at birth and 90% at 10 months. The estimated typical clearance at steady state was 10.7 L/h in a child weighing 9.8 kg co-treated with lopinavir/ritonavir, and was 12% higher in children receiving efavirenz. During coadministration of rifampicin-based antituberculosis treatment and super-boosted lopinavir in a 1:1 ratio with ritonavir, abacavir exposure decreased by 29.4%. Malnourished children living with HIV had higher abacavir exposure initially, but this effect waned with nutritional rehabilitation. An additional 18.4% reduction in clearance after the first abacavir dose was described, suggesting induction of clearance with time on lopinavir/ritonavir-based therapy. Finally, absorption of the fixed dose combination tablet was 24% slower than the abacavir liquid formulation | ||
| 520 | |a CONCLUSION: In this pooled analysis we found that children on lopinavir/ritonavir or efavirenz had similar abacavir exposures, while concomitant TB treatment and super-boosted lopinavir gave significantly reduced abacavir concentrations | ||
| 650 | 4 | |a Journal Article | |
| 650 | 4 | |a Meta-Analysis | |
| 650 | 4 | |a Research Support, Non-U.S. Gov't | |
| 650 | 4 | |a abacavir | |
| 650 | 4 | |a children | |
| 650 | 4 | |a efavirenz | |
| 650 | 4 | |a lopinavir | |
| 650 | 4 | |a malnutrition | |
| 650 | 4 | |a population pharmacokinetics | |
| 650 | 4 | |a rifampicin | |
| 650 | 7 | |a Anti-HIV Agents |2 NLM | |
| 650 | 7 | |a Dideoxynucleosides |2 NLM | |
| 650 | 7 | |a Lopinavir |2 NLM | |
| 650 | 7 | |a 2494G1JF75 |2 NLM | |
| 650 | 7 | |a Ritonavir |2 NLM | |
| 650 | 7 | |a O3J8G9O825 |2 NLM | |
| 650 | 7 | |a abacavir |2 NLM | |
| 650 | 7 | |a WR2TIP26VS |2 NLM | |
| 700 | 1 | |a McIlleron, Helen |e verfasserin |4 aut | |
| 700 | 1 | |a Burger, David |e verfasserin |4 aut | |
| 700 | 1 | |a Gibb, Diana |e verfasserin |4 aut | |
| 700 | 1 | |a Rabie, Helena |e verfasserin |4 aut | |
| 700 | 1 | |a Lee, Janice |e verfasserin |4 aut | |
| 700 | 1 | |a Lallemant, Marc |e verfasserin |4 aut | |
| 700 | 1 | |a Cotton, Mark F |e verfasserin |4 aut | |
| 700 | 1 | |a Archary, Moherndran |e verfasserin |4 aut | |
| 700 | 1 | |a Hennig, Stefanie |e verfasserin |4 aut | |
| 700 | 1 | |a Denti, Paolo |e verfasserin |4 aut | |
| 773 | 0 | 8 | |i Enthalten in |t British journal of clinical pharmacology |d 1974 |g 88(2022), 2 vom: 15. Feb., Seite 403-415 |w (DE-627)NLM000097799 |x 1365-2125 |7 nnns |
| 773 | 1 | 8 | |g volume:88 |g year:2022 |g number:2 |g day:15 |g month:02 |g pages:403-415 |
| 856 | 4 | 0 | |u http://dx.doi.org/10.1111/bcp.14984 |3 Volltext |
| 912 | |a GBV_USEFLAG_A | ||
| 912 | |a GBV_NLM | ||
| 951 | |a AR | ||
| 952 | |d 88 |j 2022 |e 2 |b 15 |c 02 |h 403-415 | ||