The Pharmacokinetics (PK) and Safety of A Single Dose of Adefovir Dipivoxil in Children and Adolescents with Chronic Hepatitis B
ADV 10 mg is approved for the treatment of chronic hepatitis B (CHB) in adults. ADV as an oral suspension is in development for the treatment of CHB in pediatrics.
The objective of the current study was to evaluate the PK of adefovir in pediatrics and establish dosing for patients aged 2-17 years.
47 HBeAg+ CHB patients with serum HBV DNA ≥5 log10 copies/mL (Roche Amplicor Monitor? PCR), and ALT ≥1.2xULN enrolled.
Subjects 2-11 years received single doses of 0.14 mg/kg and 0.3 mg/kg (2x adult dose) in a cross over design (7-day washout).
Subjects 12-17 years received a single dose of 10 mg ADV. Drug levels were assessed at: 0, 0.5, 1, 2, 4, 6, 8, 12 and 24 hours post-dose.
Results
45 subjects dosed. PK parameters of adefovir in subjects ≥12 years were similar to adults. In subjects 2-6 and 7-11 years, 0.14mg/kg resulted in relative underexposure; 0.3 mg/kg resulted in a higher Cmax but a comparable AUC0-∞ to adults.
No clinically significant adverse events except one SAE unrelated to treatment were observed.
Conclusion
The pediatric dose for phase 3 studies is 0.3 mg/kg for patients 2-6, 0.25 mg/kg for patients 7-11 and 10 mg for patients 12-17 years. ADV was well tolerated at all doses.
04/16/04
Reference
E Sokal and others. The Pharmacokinetics (PK) and Safety of A Single Dose of Adefovir Dipivoxil in Children and Adolescents (Aged 2-17) with Chronic Hepatitis B. Abstract 445 (poster). 39th EASL. April 14-18, 2004. Berlin, Germany.
[此贴子已经被作者于2004-4-16 14:35:27编辑过]
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发表于 2004-4-17 03:32
