title: Pharmacokinetic allometric scaling of oligonucleotides.
abstract: The objective of this study was to evaluate the predictive performance of interspecies scaling of oligonucleotides to predict clearance and volume of distribution at steady state in humans from animal data. The human pharmacokinetic parameters were predicted using 1, 2, or at least 3 animal species. The results of the study indicated that the pharmacokinetic parameters of oligonucleotides can be predicted with reasonable accuracy in humans when at least 3 animal species are employed. On the other hand, allometric scaling based on 1 or 2 species or fixed coefficient or fixed exponent can be erratic and unreliable. Further work should be conducted in this direction.
authors.affiliation: Office of Blood Review & Research (OBRR), Center for Biologic Evaluation and Research , Food & Drug Administration, Rockville, Maryland 20852, USA. iftekhar.mahmood@fda.hhs.gov
authors.forename: Iftekhar
authors.initials: I
authors.lastname: Mahmood
mesh_terms: D000465:Algorithms; D000818:Animals; D001835:Body Weight; D003198:Computer Simulation; D004285:Dogs; D000882:Haplorhini; D006801:Humans; D008657:Metabolic Clearance Rate; D051379:Mice; D008954:Models, Biological; D009841:Oligonucleotides / Q000493:pharmacokinetics*; D051381:Rats; D013045:Species Specificity
chemical_list: D009841:Oligonucleotides