Animal models parenteral administration

Whole animal studies are generally necessary to determine the effect of the drug on organ systems and disease models. Cardiovascular and renal function studies of all new drugs are generally first performed in normal animals. Where appropriate, studies on disease models are performed. For a candidate antihypertensive drug, animals with hypertension would be treated to see whether blood pressure was lowered in a dose-related manner and to characterize other effects of the compound. Evidence would be collected on duration of action and efficacy after oral and parenteral administration. 

This chapter has described the pharmacokinetics of PT 2 -MOE partially modified ASO following parenteral administration, and has shown that ASOs in this chemical class distribute extensively to many tissue types, with prolonged half-lives. Moreover, exposure-response relationships have been established in both animal models and humans. However, there are a few tissues to which parenter-ally administered oligonucleotides do not distribute, or are distributed minimally these include brain, muscle, eyes, and skin. Consequently, ASOs targeted to these tissues will require local delivery, as outlined in Chapter 10. 

MK-0911 has shown activity in animal models following intravenous, intraperitoneal, and oral administration. However, the oral route requires doses higher by as much as 300-fold than the parenteral routes... 

Fujita, T, Tanaka, T, Yonemasu, Y, Cendes, E, Cashman, N.R., and Andermann, F. 1996. Electroclinical and pathological studies after parenteral administration of domoic acid in freely moving nonanesthetized rats an animal model of excito-toxicity. J Epilepsy 9, 87-93. 

Intravenous administration may be used to treat seizures. However, rectal suppositories have been used on occasion, if there is no parenteral access. The dermal and inhalational routes have been used in animal models, but are not conventionally used in clinical situations. 

An alternative option for the treatment of hypertension was pursued with direct renin inhibitors. [21 ] Monoclonal antibodies, directed against renin, had shown blood pressure lowering properties in animal models. However, due to their immunogenicity and mandatory parenteral administration, they proved not suitable for long term treatment. 

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