Antisense oligonucleotide inhibitors for the treatment of cancer: 1. Pharmacokinetic properties of phosphorothioate oligodeoxynucleotides
Geary, R.S.; Leeds, J.M.; Henry, S.P.; Monteith, D.K.; Levin, A.A.
Anti-Cancer Drug Design 12(5): 383-393
1997
ISSN/ISBN: 0266-9536 PMID: 9236854 Document Number: 3372
The data presented in this document suggest that the pharmacokinetics of phosphorothioate oligodeoxynucleotides are independent of sequence, and that the pattern of distribution to organs is similar across species and independent of the route of administration (i.v. versus s.c.). The observed plasma pharmacokinetics (Cmax, AUC, clearance) appear to be more closely related to body weight across species than surface area. This correlation between species provides a level of confidence that preclinical animal models can be predictive of exposure in the clinic, and thus, exposure can be managed based on the knowledge gained in the non-clinical studies. As will be further developed in the following review, a close correlation between oligonucleotide exposure and toxicities has been observed in preclinical studies.
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