European Journal of Clinical Pharmacology

, Volume 66, Issue 10, pp 1017–1023 | Cite as

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

  • Doaa Elsherbiny
  • Yuan Ren
  • Helen McIlleron
  • Gary Maartens
  • Ulrika S. H. Simonsson
Pharmacokinetics and Disposition

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/m2 (274, 309) and ritonavir 301 mg/m2 (286, 309) twice daily. After TB treatment completion the children received standard doses of lopinavir/ritonavir 4:1 (median [IQR] lopinavir dose 289 mg/m2 [286, 303] twice daily) as did those without TB (median [IQR] lopinavir dose 265 mg/m2 [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 Cmin 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.

Keywords

Lopinavir Ritonavir Pharmacokinetics HIV Tuberculosis 

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Copyright information

© Springer-Verlag 2010

Authors and Affiliations

  • Doaa Elsherbiny
    • 1
  • Yuan Ren
    • 2
  • Helen McIlleron
    • 2
  • Gary Maartens
    • 2
  • Ulrika S. H. Simonsson
    • 1
  1. 1.Department of Pharmaceutical BiosciencesUppsala UniversityUppsalaSweden
  2. 2.Division of Clinical Pharmacology, Department of MedicineUniversity of Cape TownCape TownSouth Africa

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