This view is further supported by Davies (1992) who demonstrated that early interim
blood samples can provide valuable information on the effects of drugs on clinical
pathology. In the experiment described, blood samples taken at the end of a 3-month dog
study had normal plasma alkaline phosphatase (ALP) and aspartate aminotransferase
(AST) activities but there was a slight increase in alanine aminotransferase (ALT)
activity; morphologically the liver was normal. Early blood samples taken during weeks
1 and 2 exhibited elevated ALP and ALT activities and the mean ALT value at week 2
showed more than a 20-fold increase compared to the pre-study results. These elevated
values persisted for at least 5 weeks but, despite continued dosing, the liver had virtually
recovered by the end of the 3-month dosing period. If terminal samples only had been
taken in this study, valuable information would have been missed. Similar examples can
be cited for haematological changes following the administration of a cytotoxic drug that
has an effect on bone marrow. With such compounds, the haematological profile goes
through a cycle of reduced white and red cell counts followed by a recovery to pre-dose
values