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Objective: Oseltamivir (Ro 64-0796) is an ester prodrug of the active metabolite Ro 64-0802 (oseltamivir carboxylate), a potent and selective inhibitor of the neuraminidase enzyme of influenza virus. In this study we report the pharmacokinetics of oseltamivir in healthy children volunteers (study 1) and in children with influenza (study 2). Study Participants and Methods: In study 1, an open-label, single dose study, serial plasma samples were obtained from a total of 18 healthy children (5 to 18 years) who were grouped by age (n = 6 per group) and received single oral doses of oseltamivir 2 mg/kg. In study 2, a randomised, placebo controlled phase III study in paediatric children (1 to 12 years) presenting with influenza symptoms, 199 pharmacokinetic sparse samples were obtained from 87 patients, and serial samples were obtained from 5 patients. Pooled data were compared with those from adult studies. Results: Children (1 to 12 years) eliminated the active metabolite faster than both adolescents (13 to 18 years) and adults, resulting in lower exposure to the active drug. In these children, oseltamivir 2 mg/kg twice daily resulted in drug exposures within the range associated with tolerability and efficacy in adults administered approximately 1 mg/kg twice daily. Unit doses of oseltamivir 30, 45 and 60mg oral suspension are recommended twice daily in children weighing ≤15kg (or ≤33lb, aged 1 to 3 years), >15 to 23kg (or >33 to 51lb, aged 4 to 7 years) and >23 to 40kg (or >51 to 88lb, aged 8 to 12 years), respectively. A 75mg capsule may be a viable dosage formulation in children (e.g. over 8 years of age) who are able to swallow solid dosage forms. Conclusions: Young children cleared the active metabolite oseltamivir carboxylate at a faster rate than older children and adults. Convenient administration recommendations for the oseltamivir oral suspension in children are possible to maintain drug exposure within the target window. [ABSTRACT FROM AUTHOR]

Background/aim: Understanding the temporal change and GFR prediction is important to assess renal function in elderly subjects.Method: 13 male and 18 female healthy elderly subjects (mean 62 year; range 55-75 year) were admitted for 4 days. CG-CrCL was normalized to 1.73 per m2. GFR was predicted by MDRD study's 6-variable formula (MDRD1), and 4-variable formula (MDRD2). uCrCL was calculated from 24-h urinary collection at 3 time intervals.Result & discussion: The mean ±SD results were presented. GFR MDRD1 and MDRD2 had a high correlation (R2=0.9463). CG-CrCL correlated well with GFR MDRD2 (R2=0.4427), and were consistent with literature GFR of ∼80mL/min (60-69 year). uCrCL over estimated GFR. Urine outputs were higher by ∼20%, and all renal assessments were higher by ∼10-20 mL/min for the 2nd and 3rd intervals versus on the first day of admission (−24 to 0 h). (Table)Conclusions: Measured uCrCL over estimated GFR, while CG-CrCL and GFR MDRD provided better GFR prediction in elderly subjects. Hydration status contributed to higher renal clearance, and inter-day variability.Clinical Pharmacology & Therapeutics (2005) 79, P3–P3; doi: 10.1016/j.clpt.2005.12.008 [ABSTRACT FROM AUTHOR]