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JAC Advance Access published online on August 13, 2003
Journal of Antimicrobial Chemotherapy, doi:10.1093/jac/dkg391
© 2003 by The British Society for Antimicrobial Chemotherapy
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© 2003 The British Society for Antimicrobial Chemotherapy

Brief report

Changes in indinavir exposure over time: a case study in six HIV-1-infected children

P. L. A. Fraaij 1 , A. S. Bergshoeff 2 , A. M. C. van Rossum 1 , N. G. Hartwig 1 , D. M. Burger 2 , and R. de Groot 1 *

1 Department of Pediatrics, Erasmus MC/Sophia Children's Hospital, Rotterdam;
2 Department of Clinical Pharmacy, University Medical Center, Nijmegen, The Netherlands

* Corresponding author. E-mail: r.degroot{at}erasmusmc.nl.

Received 11 April 2003 ; revised 23 June 2003 ; accepted 25 June 2003

Abstract

Objective: To study changes in indinavir exposure over time in HIV-1-infected children.

Materials and methods: Protease inhibitor (PI)-naive HIV-1-infected children were treated with indinavir, zidovudine and lamivudine. Steady-state plasma pharmacokinetic (PK) sampling was carried out as standard of care. The AUC0-8 was targeted between 15 and 30 mgxh/L. PK sampling was repeated after dosage adjustment until the AUC0-8 reached target values. Patients were included when the time interval between PK samplings was >=2 years and differences in dosage/m2 < 10% between PK samplings 1 and 2. Corrections of dose for changes in body size were carried out.

Results: Six children were enrolled with a median age of 5.2 years (range 1.7-13.6 years). All had a viral load below 500 copies/mL. The geometric mean (GM) of the AUC0-8 decreased from 25.3 mgxh/L at the first PK-day to 19.1 mgxh/L at the second PK-day [geometric mean ratio (GMR): 0.76 (95% C.I.: 0.48-1.20)]. The GM of Cmax decreased from 11.8 to 10.4 mg/L [GMR: 0.88 (95% C.I.: 0.59-1.32)]. The GM of Cmin decreased from 0.08 to 0.07 mg/L [GMR: 0.86 (95% C.I.: 0.62-1.18)]. All children had an AUC0-8 above 15 mgxh/L on the first PK-day; three had an AUC0-8 below 15 mgxh/L on the second PK-day. In two of these three children, the plasma viral load was >500 copies/mL.

Conclusion: Changes in indinavir exposure were observed over time. In two patients, decreased indinavir exposure was associated with virological failure. Therapeutic drug monitoring should be carried out over time since this may prevent subtherapeutic dosing in children.

Keywords: pharmacokinetic analysis, age, development, paediatric HIV/AIDS, pharmacokinetics, protease inhibitors, indinavir
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