[bembem_c]

Pharmacokinetics (in this case: half-life in the central(venous) compartment, totally neglecting the distribution to the site of primary activity, the CNS) is only half of the truth.

You have to consider pharmacodynamics: where is the site of action located, where are the receptors located. And how well do caffein and paraxanthine distribute to this compartment.

Soiler: Most metabolites are more hydrophilic than respective parent compounds (biological sense of metabolism: to increase renal clearance of xenobiotics). Therefore, receptor affinity alone tells you little about the relative contribution of any metabolite for the pharmacological effect observed.

And to complicate things even more: Long-half life metabolites are only ONE potential reason for prolonged biological effects.