BACKGROUND: In children younger than 2 years of age vertically infected with HIV-1, the recommended pediatric dosing regimen for nelfinavir (20 to 30 mg/kg three times a day) provides insufficient drug exposure. This study was conducted to determine the steady state pharmacokinetics of nelfinavir and its active metabolite, M8, in this population. METHODS: Fourteen infants (2.3 to 8.5 months) underwent 18 intensive pharmacokinetic studies of nelfinavir and M8 at steady state. Nelfinavir and M8 concentrations were measured by high performance liquid chromatography coupled with mass spectrometry, and individual pharmacokinetic values were determined. RESULTS: A mean nelfinavir daily dose of 135.7 +/- 18.8 mg/kg (twice or three times a day) resulted in median C(min), C(max), area under the plasma concentration-time curve (AUC(0-24 h)) and CL/ for nelfinavir of 0.627 mg/l, 2.39 mg/l, 30.6 mg*h/l and 4.2 liters/h/kg, respectively. When normalized for a daily dose of nelfinavir of 150 mg/kg/day, 16.7% of C(max) and 27.8% of AUC(0-24 h) values were below the tenth percentile for adult values. CONCLUSIONS: During the first year of life, nelfinavir requirement is much higher than in older children and adults to obtain similar drug exposure. The mechanisms underlying such differences may involve higher first past metabolism and/or drug interactions or might be related to feeding conditions.
BACKGROUND: In children younger than 2 years of age vertically infected with HIV-1, the recommended pediatric dosing regimen for nelfinavir (20 to 30 mg/kg three times a day) provides insufficient drug exposure. This study was conducted to determine the steady state pharmacokinetics of nelfinavir and its active metabolite, M8, in this population. METHODS: Fourteen infants (2.3 to 8.5 months) underwent 18 intensive pharmacokinetic studies of nelfinavir and M8 at steady state. Nelfinavir and M8 concentrations were measured by high performance liquid chromatography coupled with mass spectrometry, and individual pharmacokinetic values were determined. RESULTS: A mean nelfinavir daily dose of 135.7 +/- 18.8 mg/kg (twice or three times a day) resulted in median C(min), C(max), area under the plasma concentration-time curve (AUC(0-24 h)) and CL/ for nelfinavir of 0.627 mg/l, 2.39 mg/l, 30.6 mg*h/l and 4.2 liters/h/kg, respectively. When normalized for a daily dose of nelfinavir of 150 mg/kg/day, 16.7% of C(max) and 27.8% of AUC(0-24 h) values were below the tenth percentile for adult values. CONCLUSIONS: During the first year of life, nelfinavir requirement is much higher than in older children and adults to obtain similar drug exposure. The mechanisms underlying such differences may involve higher first past metabolism and/or drug interactions or might be related to feeding conditions.
Authors: D M Gibb; T Duong; P A Tookey; M Sharland; G Tudor-Williams; V Novelli; K Butler; A Riordan; L Farrelly; J Masters; C S Peckham; D T Dunn Journal: BMJ Date: 2003-11-01
Authors: Esse N Menson; A Sarah Walker; Mike Sharland; Carole Wells; Gareth Tudor-Williams; F Andrew I Riordan; E G Hermione Lyall; Diana M Gibb Journal: BMJ Date: 2006-05-20
Authors: Salvador Resino; Beatriz Larrú; Jose Maria Bellón; Rosa Resino; Maria Isabel de José; Marisa Navarro; Juan Antonio Léon; José Tomás Ramos; Maria José Mellado; Maria Angeles Muñoz-Fernández Journal: BMC Infect Dis Date: 2006-07-11 Impact factor: 3.090
Authors: Nicole Ngo-Giang-Huong; Linda Wittkop; Ali Judd; Peter Reiss; Tessa Goetghebuer; Dan Duiculescu; Antoni Noguera-Julian; Magdalena Marczynska; Carlo Giacquinto; Luminita Ene; Jose T Ramos; Cristina Cellerai; Thomas Klimkait; Benedicte Brichard; Niels Valerius; Caroline Sabin; Ramon Teira; Niels Obel; Christoph Stephan; Stéphane de Wit; Claire Thorne; Diana Gibb; Christine Schwimmer; Maria Athena Campbell; Deenan Pillay; Marc Lallemant Journal: BMC Infect Dis Date: 2016-11-08 Impact factor: 3.090