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PEDIATRICS Vol. 112 No. 3 September 2003, pp. e220-e227

ELECTRONIC ARTICLE

Nelfinavir Pharmacokinetics in Stable Human Immunodeficiency Virus-Positive Children: Pediatric AIDS Clinical Trials Group Protocol 377

Leslie Carstensen Floren, PharmD*, Andrew Wiznia, MD{ddagger}, Sandra Hayashi, PharmD*, Anura Jayewardene, PhD*, Kenneth Stanley, PhD§, George Johnson, MD||, Sharon Nachman, MD, Paul Krogstad, MD#, Francesca T. Aweeka, PharmD* the Pediatric ACTG 377 Protocol Team

* Drug Research Unit, Department of Clinical Pharmacy, University of California, San Francisco, California
{ddagger} Jacobi Medical Center, Bronx, New York
§ Harvard School of Public Health, Boston, Massachusetts
|| Medical University of South Carolina, Charleston, South Carolina
SUNY Health Sciences Center, Stony Brook, New York
# University of California, Los Angeles, California

Objective. Pharmacokinetic data obtained from children who have human immunodeficiency virus (HIV) infection are essential for the safe and effective use of antiretroviral agents in pediatric populations. The objective of this study was to assess the impact of body weight on the pharmacokinetic disposition of nelfinavir (NFV) in the absence and presence of nevirapine (NVP) and compare the pharmacokinetic profiles of twice-daily (BID) and three-times-daily (TID) NFV regimens.

Methods. This was an intensive pharmacokinetic substudy nested in a phase II, multicenter, randomized, open-label trial. Forty-five HIV-infected children receiving NFV 30 mg/kg TID and 6 HIV-infected children receiving NFV 55 mg/kg BID were enrolled in this study and assigned to 1 of 4 stavudine-containing regimens, 3 containing NFV and 2 containing NVP. Area under the plasma concentration-time curves from 0 to 8 hours (AUC0–8 hours) and from 0 to 12 hours (AUC0–12 hours) for the TID and BID regimens, respectively, were determined. For comparative purposes, the AUC0–24 hours was also calculated for each regimen.

Results. NFV exposure in the absence of NVP was decreased in children who were <25 kg compared with those who were >25 kg (a 2.6-fold difference in median AUC0–8 hours). NFV pharmacokinetics in the presence of NVP did not differ between the <25 kg and >25 kg groups. The AUC0–24 hours for children who were <30 kg and on NFV BID was comparable to the AUC0–24 hours for children who were >25 kg and on NFV TID but was 2.7-fold greater than AUC0–24 hours for children who were <25 kg and on NFV TID.

Conclusions. NFV in the absence of NVP resulted in less than half the drug exposure in children who were <25 kg compared with children who were >25 kg. NFV dosed at 55 mg/kg BID in children who are <30 kg provides comparable exposure to that measured in children who are >25 kg and receiving NFV 30 mg/kg TID.

Key Words: pharmacokinetics • nelfinavir • children • HIV • protease inhibitor • nevirapine

Abbreviations: PI, protease inhibitor • HIV, human immunodeficiency virus • NFV, nelfinavir • TID, three times daily • NNRTI, nonnucleoside reverse transcriptase inhibitor • NVP, nevirapine • BID, twice daily • NRTI, nucleoside reverse transcriptase inhibitor • PACTG, Pediatric AIDS Clinical Trials Group • d4T, stavudine • 3TC, lamivudine • AUC, area under the plasma concentration-time curve • CL/F, apparent clearance • Cmin, minimum plasma concentration

Received for publication Dec 23, 2002; Accepted May 7, 2003.


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