Pharmacokinetics of adjusted-dose 8-hourly lopinavir/ritonavir in HIV-infected children co-treated with rifampicin.
J Antimicrob Chemother
; 74(8): 2347-2351, 2019 08 01.
Article
em En
| MEDLINE
| ID: mdl-31081020
ABSTRACT
OBJECTIVES:
To evaluate the proportion of children with lopinavir Cmin ≥1 mg/L when receiving a novel 8-hourly lopinavir/ritonavir dosing strategy during rifampicin co-treatment.METHODS:
HIV-infected children on lopinavir/ritonavir and rifampicin were enrolled in a prospective pharmacokinetic study. Children were switched from standard-of-care lopinavir/ritonavir-41 with additional ritonavir (11 ratio) twice daily to 8-hourly lopinavir/ritonavir-41 using weight-banded dosing. Rifampicin was dosed at 10-20 mg/kg/day. After 2 weeks, plasma samples were collected â¼2, 4, 6, 8 and 10 h after the morning lopinavir/ritonavir-41 dose, ALT was obtained to assess safety and treatment was switched back to standard of care. ClinicalTrials.gov registration number NCT01637558.RESULTS:
We recruited 11 children in two weight bands 5 (45%) were 10-13.9 kg and received 20-24 mg/kg/dose of lopinavir and 6 (55%) children weighed 6-9.9 kg and received 20-23 mg/kg/dose of lopinavir. The median age was 15 months (IQRâ=â12.6-28.8 months). The median (IQR) lopinavir Cmin was 3.0 (0.1-5.5) mg/L. Seven (63.6%) of the 11 children had Cmin values ≥1 mg/L. Children with a lopinavir mg/kg dose below the median 21.5 were more likely to have Cmin <1 mg/L (Pâ=â0.02). There was a strong positive correlation between lopinavir and ritonavir concentrations. No associations were found between lopinavir AUC2-10 and age, sex, weight, nutritional status or mg/kg/dose of lopinavir.CONCLUSIONS:
These data do not support the use of 8-hourly lopinavir/ritonavir at studied doses. Evaluation of higher doses is needed to optimize treatment outcomes of TB and HIV in young children.
Texto completo:
1
Base de dados:
MEDLINE
Assunto principal:
Rifampina
/
Tuberculose
/
Infecções por HIV
/
Ritonavir
/
Fármacos Anti-HIV
/
Lopinavir
/
Antibióticos Antituberculose
Idioma:
En
Ano de publicação:
2019
Tipo de documento:
Article
País de afiliação:
África do Sul