Abacavir Exposure in Children Cotreated for Tuberculosis with Rifampin and Superboosted Lopinavir-Ritonavir
Date
2020-05
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Abstract
ABSTRACT In children requiring lopinavir coformulated with ritonavir in a 4:1 ratio (lopinavir-ritonavir-4:1) and rifampin, adding ritonavir to achieve a 4:4 ratio with lopi-navir (LPV/r-4:4) overcomes the drug-drug interaction. Possible drug-drug interac-tions within this regimen may affect abacavir concentrations, but this has never been studied. Children weighing 15 kg needing rifampin and LPV/r-4:4 were enrolled in a pharmacokinetic study and underwent intensive pharmacokinetic sampling on 3 visits: (i) during the intensive and (ii) continuation phases of anti-tuberculosis treatment with LPV/r-4:4 and (iii) 1 month after antituberculosis treat-ment completion on LPV/r-4:1. Pharmacometric modeling and simulation were used to compare exposures across weight bands with adult target exposures. Eighty-seven children with a median (interquartile range) age and weight of 19 (4 to 64) months and 8.7 (3.9 to 14.9) kg, respectively, were included in the abacavir analysis. Abacavir pharmacokinetics were best described by a two-compartment model with first-order elimination and transit compartment absorption. After allometric scaling adjusted for the effect of body size, maturation could be identified: clearance was predicted to be fully mature at about 2 years of age and to reach half of this mature value at about 2 months of age. Abacavir bioavailability decreased 36% during treat-ment with rifampin and LPV/r-4:4 but remained within the median adult recom-mended exposure, except for children in the 3- to 4.9-kg weight band, in which the exposures were higher. The observed predose morning trough concentrations were higher than the evening values. Though abacavir exposure significantly decreased dur-ing concomitant administration of rifampin and LPV/r-4:4, it remained within acceptable ranges. (This study is registered in ClinicalTrials.gov under identifier NCT02348177.)
Description
CITATION:abie H, Tikiso T, Lee J, Fairlie L, Strehlau R, Bobat R, Liberty A, McIlleron H, Andrieux-Meyer I, Cotton M, Lallemant M, Denti P. 2020. Abacavir exposure in children cotreated for tuberculosis with rifampin and superboosted lopinavir-ritonavir. Antimicrob Agents Chemother 64:e01923-19. https://doi .org/10.1128/AAC.01923-19.
The original publication us available:aac.asm.org
The original publication us available:aac.asm.org
Keywords
abacavir, rifampin, children, lopinavir