tetano
Editor, Senior Moderator
Clin Pharmacol Ther. 2020 Jan 20. doi: 10.1002/cpt.1791. [Epub ahead of print] [h=1]Mechanistic Population Pharmacokinetic Model of Oseltamivir and Oseltamivir Carboxylate Accounting for Physiological Changes to Predict Exposures in Neonates and Infants.[/h]
Gibiansky L[SUP]1[/SUP], Ravva P[SUP]2[/SUP], Parrott NJ[SUP]3[/SUP], Bhardwaj R[SUP]4[/SUP], Zwanziger E[SUP]3[/SUP], Grimsey P[SUP]5[/SUP], Clinch B[SUP]6[/SUP], Sturm S[SUP]3[/SUP].
[h=3]Author information[/h]
[h=3]Abstract[/h] A mechanistic population-pharmacokinetic model was developed to predict oseltamivir exposures in neonates and infants accounting for physiological changes during the first 2 years of life. The model included data from 13 studies, comprising 436 subjects with normal renal function (317 pediatric subjects [≥ 38 weeks postmenstrual age (PMA), ≥ 13 days old] and 119 adult subjects < 40 years). Concentration-time profiles of oseltamivir and its active metabolite, oseltamivir carboxylate (OC), were characterized by a four-compartment model, with absorption described by three additional compartments. Renal maturational changes were implemented by description of OC clearance with allometric function of weight and Hill function of postmenstrual age. Clearance of OC increased with weight up to 43 kg (allometric coefficient 0.75). Half the adult OC clearance was reached at a PMA of 45.6 weeks (95% CI: 41.6-49.6) with a Hill coefficient of 2.35 (95% CI: 1.67-3.04). The model supports the EU/USA-approved 3 mg/kg twice-daily oseltamivir dose for infants < 1 year (PMA ≥ 38 weeks) and allows prediction of exposures in preterm neonates.
? 2020 The Authors Clinical Pharmacology & Therapeutics ? 2020 American Society for Clinical Pharmacology and Therapeutics.
[h=4]KEYWORDS:[/h] Influenza; neonates; oseltamivir; pharmacokinetics
PMID: 31957010 DOI: 10.1002/cpt.1791
Gibiansky L[SUP]1[/SUP], Ravva P[SUP]2[/SUP], Parrott NJ[SUP]3[/SUP], Bhardwaj R[SUP]4[/SUP], Zwanziger E[SUP]3[/SUP], Grimsey P[SUP]5[/SUP], Clinch B[SUP]6[/SUP], Sturm S[SUP]3[/SUP].
[h=3]Author information[/h]
[h=3]Abstract[/h] A mechanistic population-pharmacokinetic model was developed to predict oseltamivir exposures in neonates and infants accounting for physiological changes during the first 2 years of life. The model included data from 13 studies, comprising 436 subjects with normal renal function (317 pediatric subjects [≥ 38 weeks postmenstrual age (PMA), ≥ 13 days old] and 119 adult subjects < 40 years). Concentration-time profiles of oseltamivir and its active metabolite, oseltamivir carboxylate (OC), were characterized by a four-compartment model, with absorption described by three additional compartments. Renal maturational changes were implemented by description of OC clearance with allometric function of weight and Hill function of postmenstrual age. Clearance of OC increased with weight up to 43 kg (allometric coefficient 0.75). Half the adult OC clearance was reached at a PMA of 45.6 weeks (95% CI: 41.6-49.6) with a Hill coefficient of 2.35 (95% CI: 1.67-3.04). The model supports the EU/USA-approved 3 mg/kg twice-daily oseltamivir dose for infants < 1 year (PMA ≥ 38 weeks) and allows prediction of exposures in preterm neonates.
? 2020 The Authors Clinical Pharmacology & Therapeutics ? 2020 American Society for Clinical Pharmacology and Therapeutics.
[h=4]KEYWORDS:[/h] Influenza; neonates; oseltamivir; pharmacokinetics
PMID: 31957010 DOI: 10.1002/cpt.1791