Most human metabonomic studies are performed in clinical phase I trials. Advantages of human studies compared to animal studies are the costs and availabilty of urine and plasma samples. Whereas for animal studies the costs of sampling urine in metabolic cages are quite high, urine is collected in clinical studies anyway. Usually animal plasma is obtained only at the end of the study, whereas plasma samples are obtained in regular intervals during clinical studies.
A drawback of human studies compared to animal studies is the difference between individuals. Usually the variance between humanin individuals is a lot higher than the variance between different samples from the same individual. Therefore it is important to reference the individuals to themselves using pre-dose samples. A very important factor of human studies is the influence of nutrition. Food and drinks can dramatically influence the metabolic profile. For example the consummation of fish significantly increases the excretion of the endogenous metabolite trimethylaminoxide into urine. Another example is the excretion of ethanol or mannitol. Therefore standardized food during animal studies helps to reduce unwanted variances of the metabolic profiles. In clinical trials standardized food is desirable but not always feasible.