Renal function safety pharmacology

Defines the objective of safety pharmacology studies to Anon23 reveal functional effects on major physiological systems (e.g., cardiovascular, respiratory, renal, and central nervous systems)... 

With regard to Safety Pharmacology, testing of the vital function such as cardiovascular, respiratory and CNS functions is recommended, but S 6 also mentions renal function, which from today s perspective would not be necessary before first administration of a compound in humans if there is no specific concern. 

In safety pharmacology, a number of renal functional tests, such as creatinine and electrolyte measurements, can be supported by most clinical chemistry laboratories (Kinter, Gossett, and Kerns 1994 Seuter 1996 ICH 2000). In some of the later chapters discussing assessments of hepatotoxicity and renal toxicity, a few functional tests are mentioned. Although it may be desirable to include function tests in repeated-dose toxicity studies, given the additional and sometimes invasive procedures, these tests may be better performed by incorporation into single-dose toxicity studies or separate additional studies (Matsuzawa et al. 1997). 

Table 7.5 presents the basic guidance provided by the International Conference on Harmonisation of Technical Requirements for Registration of Pharmaceuticals for Human Use (ICH) for renal safety pharmacology evaluation of new drugs. These evaluations are noncore and therefore not required prior to first-in-man studies. It is essential that intact animals be used in such evaluations, but it must be kept in mind that there are species differences in responses [12,13] and that renal function is readily influenced by anesthesia [14,15]. 

As stated previously, the ICH S7A recommendations state that the precUnical investigatiOTi of renal effects under the remit of safety pharmacology is supplementary and should only be performed when renal safety issues are suspected on a cause for concern basis (Anon. 2001). Therefore, assessment of renal function might not be performed by all companies. 

If there is an overriding cause for concern with regard to nephrotoxicity, then a stand-alone SP renal study should be performed. This could take the form of a standard design safety pharmacology renal study or a study after single or repeat doses of compomid which could include detailed assessments of renal function such as assessment of renal reserve or hemodynamic function (Valentin and Hammond 2006). 

The five organ functions assessed in safety pharmacology are the cardiovascular system, nervous system, respiratory system, gastrointestinal system and renal system. To these we would add general systemic metabolic functions, as these are amenable to collectiOTi of at least some biochemical and physiological data. 

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