当前位置： SCI文献检索 > EUROPEAN JOURNAL OF CLINICAL PHARMACOLOGY期刊下所有文献 > Population pharmacokinetics of lopinavir in combination with rifampicin-based antitubercular treatment in HIV-infected South African children.

Population pharmacokinetics of lopinavir in combination with rifampicin-based antitubercular treatment in HIV-infected South African children.

Abstract：

PURPOSE:The population pharmacokinetics (PK) of lopinavir in tuberculosis (TB)/human immunodeficiency virus (HIV) co-infected South African children taking super-boosted lopinavir (lopinavir/ritonavir ratio 1:1) as part of antiretroviral treatment in the presence of rifampicin were compared with the population PK of lopinavir in HIV-infected South African children taking standard doses of lopinavir/ritonavir (ratio 4:1). METHODS:Lopinavir concentrations were measured in 15 TB/HIV-co-infected paediatric patients who were sampled during and after rifampicin-based TB treatment and in 15 HIV-infected children without TB. During TB therapy, the dose of ritonavir was increased to lopinavir/ritonavir 1:1 in order to compensate for the induction of rifampicin. The children received median (interquartile range=IQR) doses of lopinavir 292 mg/m(2) (274, 309) and ritonavir 301 mg/m(2) (286, 309) twice daily. After TB treatment completion the children received standard doses of lopinavir/ritonavir 4:1 (median [IQR] lopinavir dose 289 mg/m(2) [286, 303] twice daily) as did those without TB (median [IQR] lopinavir dose 265 mg/m(2) [249, 289] twice daily). RESULTS:Lopinavir oral clearance (CL/F) was about 30% lower in children without TB than in co-infected children treated with super-boosted lopinavir. However, the predicted lopinavir C(min) was above the recommended minimum therapeutic concentration during TB/HIV co-treatment in the 15 children. Lopinavir CL/F increased linearly during the dosing interval. CONCLUSIONS:Increasing the ritonavir dose to achieve a lopinavir/ritonavir ratio of 1:1 when given in combination with rifampicin-based TB treatment did not completely compensate for the enhancement of lopinavir CL/F caused by rifampicin. The time-dependent lopinavir CL/F might be due to a time-dependent recovery from ritonavir inhibition of lopinavir metabolism during the dosing interval.

journal_name

Eur J Clin Pharmacol

journal_title

European journal of clinical pharmacology

authors

Elsherbiny D,Ren Y,McIlleron H,Maartens G,Simonsson US

doi

10.1007/s00228-010-0847-9

subject

Has Abstract

pub_date

2010-10-01 00:00:00

pages

1017-23

issue

eissn

0031-6970

issn

1432-1041

journal_volume

pub_type

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Population pharmacokinetics of lopinavir in combination with rifampicin-based antitubercular treatment in HIV-infected South African children.