In vivo assays

The mainstay of evaluation of drug-induced effects on myocardial contractility has been the use of in vivo animal models. Although the dog has been the species most commonly used for this purpose, other species (pig, NHP, rodents) have been used successfully for this purpose. Whereas this once again introduces the possibility of having species-dependent effects that could have an impact on the 

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At the in vivo assay level, the classic ip-ip (iateraperitoneal) in vivo model has been replaced as a selection criteria for advancement of new dmg candidates to clinical trial. More stringent alternative models iaclude subcutaneous or subrenal capsule implantation of tumor followed by iatravenous dmg dosiag (7) and the human tumor xenograft models ia aude mice (8). 

Shelby MD, Newbold RR, Tully DB, etal. 1996. Assessing environmental chemicals for estrogenicity using a combination of in vitro and in vivo assays. Environ Health Perspect 104(12) 1296-1300. 

Clode, S.A. (2006). Assessment of in vivo assays for endocrine disruption Best practice and research. Clinical Endocrinology and Metabolism 20, 35 3. 

The research into the biological activities of chlorophylls developed over the past 20 years is also important although very few in vivo assays concerning then-potential health benefits have been performed. Far fewer studies have focused on chlorophylls in comparison to carotenoids. Efforts to stabilize chlorophylls in pro-... 

CTAs are possible in vitro alternatives to the standard approach for the assessment of carcinogenicity (the 2-year bioassay in rodents), which have been shown to be a multistage process able to model the most important stages of in vivo carcinogenesis [50]. CTAs are faster and more economic than in vivo assay and they could be a valid and useful screening tool for chemicals. 

Provide either in vitro or in vivo assay results for representative compounds, describe how the in vitro or in vivo assay protocol is performed, and describe how and why the test results demonstrate that the tested compounds exhibit a useful pharmaceutical property. Ideally, provide and link in vitro assay results to in vivo assay results that in turn demonstrate that the claimed compounds can be used to treat or prevent a disease. Describe how to administer the application s compounds and intended administration recipients (e.g., humans), including dosage amounts and dosage forms (e.g., pills, tablets, capsules), possible ways of administering the dosage... 

Matheson, D., D.Brusick, and D.Jagannath. 1978. Genetic activity of 1,1-dimethylhydrazine and methylhydrazine in a battery of in vitro and in vivo assays. Mutat. Res. 53 93-94. 

As only the soluble hydrogenase utilized NADH, in vivo assays could be applied to investigate this activity further. Hydrogen-driven MMO activities were measured to obtain information on the in vivo function of this hydrogenase. The apparent Ks for hydrogen was again 0.8 mM in both assays. Maximal rates of MMO activities were 140 nmol min 1... 

As a general rule, in vivo assays are more challenging than in vitro assays because the matrices for the samples are more complex. The most common use for in vivo assays is to measure the concentration of NCE dosed into a laboratory animal by collecting multiple sample time points, one can use the analytical results to plot the PK profile of the NCE and also obtain various PK parameters that help determine a test compound s PK properties. Preclinical PK parameters of a test compound are then used to predict its human PK parameters. Another use of in vivo assays is combining the results with pharmacodynamic (PD) observations to perform PK/PD modeling.77 82 PK/PD modeling is an important aspect of new drug discovery because it can be used to predict the exposures and durations required to determine clinical efficacy of a NCE. 

Kim SS, Kwack SJ, Lee RD et al (2005) Assessment of estrogenic and androgenic activities of tetramethrin in vitro and in vivo assays. J Toxicol Environ Health A 68 2277-2289... 

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