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.

• Authors: Doaa Elsherbiny, Yuan Ren, Helen McIlleron, Gary Maartens, Ulrika S H Simonsson
• Journal: European journal of clinical pharmacology (Eur J Clin Pharmacol) Vol. 66 Issue 10 Pg. 1017-23 (Oct 2010) ISSN: 1432-1041 [Electronic] Germany
• PMID: 20552180 (Publication Type: Journal Article, Research Support, Non-U.S. Gov't)

Chemical References

• Anti-HIV Agents
• HIV Protease Inhibitors
• Pyrimidinones
• Lopinavir
• Ritonavir
• Rifampin

Topics

• AIDS-Related Opportunistic Infections (drug therapy, metabolism)
• Anti-HIV Agents (administration & dosage, blood, pharmacokinetics)
• Child, Preschool
• Dose-Response Relationship, Drug
• Drug Administration Schedule
• Drug Therapy, Combination
• Female
• HIV Infections (drug therapy, metabolism)
• HIV Protease Inhibitors (pharmacokinetics)
• Humans
• Infant
• Lopinavir
• Male
• Pyrimidinones (administration & dosage, blood, pharmacokinetics)
• Rifampin (administration & dosage, blood, pharmacokinetics)
• Ritonavir (administration & dosage, blood, pharmacokinetics)
• South Africa
• Time Factors
• Treatment Outcome
• Tuberculosis, Pulmonary (drug therapy, metabolism)