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 receivingNFV 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 (AUC(0-8 hours)) and from 0 to 12 hours (AUC(0-12 hours)) for the TID and BID regimens, respectively, were determined. For comparative purposes, the AUC(0-24 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 AUC(0-8 hours)). NFV pharmacokinetics in the presence of NVP did not differ between the <25 kg and >25 kg groups. The AUC(0-24 hours) for children who were <30 kg and on NFV BID was comparable to the AUC(0-24 hours) for children who were >25 kg and on NFV TID but was 2.7-fold greater than AUC(0-24 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.
RCT Entities:
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-infectedchildren receiving NFV 30 mg/kg TID and 6 HIV-infectedchildren 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 (AUC(0-8 hours)) and from 0 to 12 hours (AUC(0-12 hours)) for the TID and BID regimens, respectively, were determined. For comparative purposes, the AUC(0-24 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 AUC(0-8 hours)). NFV pharmacokinetics in the presence of NVP did not differ between the <25 kg and >25 kg groups. The AUC(0-24 hours) for children who were <30 kg and on NFVBID was comparable to the AUC(0-24 hours) for children who were >25 kg and on NFV TID but was 2.7-fold greater than AUC(0-24 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.
Authors: Imke H Bartelink; Rada M Savic; Grant Dorsey; Theodore Ruel; David Gingrich; Henriette J Scherpbier; Edmund Capparelli; Vincent Jullien; Sera L Young; Jane Achan; Albert Plenty; Edwin Charlebois; Moses Kamya; Diane Havlir; Francesca Aweeka Journal: Pediatr Infect Dis J Date: 2015-03 Impact factor: 2.129
Authors: Monica Gandhi; Leslie Z Benet; Peter Bacchetti; Ann Kalinowski; Kathryn Anastos; Alan R Wolfe; Mary Young; Mardge Cohen; Howard Minkoff; Stephen J Gange; Ruth M Greenblatt Journal: J Acquir Immune Defic Syndr Date: 2009-04-15 Impact factor: 3.731
Authors: Akihiko Saitoh; Edmund Capparelli; Francesca Aweeka; Elizabeth Sarles; Kumud K Singh; Andrea Kovacs; Sandra K Burchett; Andrew Wiznia; Sharon Nachman; Terence Fenton; Stephen A Spector Journal: J Acquir Immune Defic Syndr Date: 2010-07 Impact factor: 3.731
Authors: Mina Nikanjam; Desiré Kabamba; Tim R Cressey; David Burger; Francesca T Aweeka; Edward P Acosta; Stephen A Spector; Edmund V Capparelli Journal: Antimicrob Agents Chemother Date: 2012-08-06 Impact factor: 5.191