Effect of rifampicin on lopinavir pharmacokinetics in HIV-infected children with tuberculosis.
J Acquir Immune Defic Syndr
; 47(5): 566-9, 2008 Apr 15.
Article
em En
| MEDLINE
| ID: mdl-18197120
ABSTRACT
OBJECTIVE:
Rifampicin dramatically reduces plasma lopinavir concentrations (coformulated with ritonavir in a 41 ratio). A study in healthy adult volunteers showed that this reduction could be ameliorated if additional ritonavir is given. We evaluated the effect of additional ritonavir on plasma lopinavir concentrations in HIV-infected children receiving rifampicin-based treatment for tuberculosis.METHODS:
We measured plasma lopinavir concentrations in 2 parallel groups receiving combination antiretroviral therapy that included lopinavir-ritonavir, with and without rifampicin-based antitubercular treatment. Additional ritonavir was given (lopinavir/ritonavir ratio of 11) during antitubercular treatment. Lopinavir concentrations were determined using liquid chromatography-tandem mass spectrometry.RESULTS:
There were 15 children (aged 7 months to 3.9 years) in each group. Lopinavir pharmacokinetic measures (median [interquartile range]) for children with and without rifampicin, respectively, were maximum concentration (Cmax) of 10.5 [7.1 to 14.3] versus 14.2 [11.9 to 23.5] mg/L (P = 0.018), area under the curve from 0 to 12 hours (AUC0-12) of 80.9 [50.9 to 121.7] versus 117.8 [80.4 to 176.1] mg/h/L (P = 0.036), and trough concentration (Cmin) of 3.94 [2.26 to 7.66] versus 4.64 [2.32 to 10.40] mg/L (P = 0.468). Thirteen of 15 children receiving antitubercular treatment (87%) had a lopinavir Cmin greater than the recommended minimum therapeutic concentration (1 mg/L).CONCLUSIONS:
The effect of rifampicin-based antitubercular treatment on lopinavir concentrations was attenuated by adding ritonavir to rifampicin. Although the median Cmax and AUC0-12 were lowered by 26% and 31%. respectively, the Cmin was greater than the minimum recommended concentration in most children.
Texto completo:
1
Base de dados:
MEDLINE
Assunto principal:
Pirimidinonas
/
Rifampina
/
Tuberculose
/
Infecções por HIV
/
Inibidores da Protease de HIV
/
Ritonavir
/
Antibióticos Antituberculose
Tipo de estudo:
Prognostic_studies
Limite:
Child, preschool
/
Female
/
Humans
/
Infant
/
Male
Idioma:
En
Revista:
J Acquir Immune Defic Syndr
Assunto da revista:
SINDROME DA IMUNODEFICIENCIA ADQUIRIDA (AIDS)
Ano de publicação:
2008
Tipo de documento:
Article
País de afiliação:
África do Sul