In vivo pharmacodynamics

K. C. Nishihara,T.A. Watanabe, S.K. Pan-dey, S. Bhanot, and R.S. Geary. 2002. In vivo pharmacodynamics and sub-cellular distribution of a 2-MOE-modified anti-sense oligonucleotide (ASO), ISIS 116847, targeting putative protein tyrosine phosphatase (PTEN) mRNA in mice and rats. In Annual Meeting of Society ofToxicol-ogy and Chemistry, Baltimore, Maryland. 

Francheteau, P., Steimer, J., Dubray, C., and Lavene, D., Mathematical model for in vivo pharmacodynamics integrating fluctuation of the response Application to the prolactin suppressant effect of the du-paminomimetic drug DCN 230-922, Journal of Pharmacokinetics and Biopharmaceutics, Vol. 19, No. 3, 1991, pp. 287-309. 

In islets, A-4166 causes a steep rise in insulin release followed by a slow sustained rise to twice the basal level. The insulinotropic effect is not glucose-dependent and takes place in the absence of glucose [191, 192]. The in vivo pharmacodynamic profile (rapid and short-term action) appears to result from a rapid plasma appearance and disappearance of the compound rather than an intrinsic feature of the mechanism [191]. A-4166 may be useful as therapy for NIDDM patients with secondary failure to sulphonylureas [190]. 

Van der Graaf and colleagues (25) applied the operational model in an integrated PK/PD analysis to characterize the in vivo pharmacodynamics of a series of adenosine Ai receptor agonists in rats. Of importance was the observation that the in vivo estimates of Kd and t were well correlated with direct experimental values obtained from in vitro bioassays. Therefore, assuming the system has been well described, the potential exists for predicting the time course of in vivo effects of relevant drug candidates from in vitro measurements. 

Fig. 5.6 Examples of novel small molecule and peptide radiotracers for in vivo pharmacodynamic imaging, (a) f C]ML03, an irreversible inhibitor of EGFR tyrosine kinase and potential PET marker for the receptor (b) f F]SAV03, an MMP-2 inhibi-...

FDA has responded to the threat of terrorism with a unique approach towards the development of biopharmaceuticais intended to counter the adverse effects of chemical, biological, radiological, or nuclear substances [83]. In many instances, efficacy trials in humans cannot be ethically performed (e.g., anti-bioterrorism agents). In these instances, animal data can be used in place of human data to model the in-vivo pharmacodynamics. In particular, studies in animals can provide substantial evidence of the effectiveness of biopharma-ceutical products intended for possible use to reduce or prevent the toxicities of these agents under defined circumstances. Such studies should be conducted under GLP (21 CFR 58) and are appHcable when ... 

Fang, J.Y, Leu, Y.L., Wang, YY, and Tsai, Y.H. (2002). In vitro topical application and in vivo pharmacodynamic evaluation of nonivamide hydrogels using Wistar rat as an animal model, Eur. J. Pharm. ScL, 15 417-423. 

Use of Activity-based Probes for Assessment of In vivo Pharmacodynamic Properties and Efficacy of Lead Compounds... 

Rnpenthal ID, Green CR, Alany RG (2011) Comparison of ion-activated in situ gelling systems for ocular drag delivtay. Part 2 precomeal retention and in vivo pharmacodynamic study. Int J Pharm 411 78-85... 

Jourdan G, Verwaerde P, Pathak A, Tran MA, Montastruc JL, Senard JM (2007) In vivo pharmacodynamic interactions between two drugs used in orthostatic hypotension-midodiine and dihydroergotamine. Fundam Clin Pharmacol 21 45-53... 

S. Eskandari, J. Varshosaz, M. Minaiyan, M. Tabbakhian, Brain delivery of valproic acid via intranasal administration of nanostructured lipid carriers in vivo pharmacodynamic studies using rat electroshock model, Int. J. Nanomedicine 6 (2011) 363-371. 

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