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.
Huh? Dose finding in "pharma" is based on effect and safety, both preclinical (cell culture, animals) in the beginning of development, later based on early clinical trials (in humans). No quantum terms necessary at all.
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.