Pharmacokinetics of propentofylline and the quantitation of its metabolitehydroxypropentofylline in human volunteers

Propentofylline (PPF, 3-methyl-1-(5-oxohexyl)-7-propylxanthine) has been re ported to be effective for the treatment of both vascular dementia and deme ntia of the Alzheimer type. The pharmacological effects of PPF may be exert ed via the stimulation of nerve growth factor, increased cerebral blood flo w, and inhibition of adenosine uptake. The objectives of this experiment ar e to determine the kinetic behavior of PPF, to identify, and to quantify it s metabolite in human. Blood samples were obtained from human Volunteers fo llowing oral administration of 200 mg of PPF tablets. For the identificatio n and quantification of the metabolite, 3-methyl-1-(5-hydroxyhexyl)-7-propy lxanthine (PPFOH), PPFOH was synthesized and identified by gas chromatograp hy/mass spectroscopy (GC/MS) and H-1-nuclear magnetic resonance spectroscop y. The molecular weight of synthesized metabolite is 308 dalton. The PPF an d PPFOH in plasma were extracted with diethyl ether and identified by elect ron impact GC/MS. The plasma concentrations of PPF and PPFOH were determine d by gas chromatography/nitrogen phosphorus detector in plasma and their ph armacokinetic parameters were determined. The mean half-life of PPF was 0.7 4 hr. The areas under the curve (AUCs) of PPF and PPFOH were 508 and 460 ng .hr/ml, respectively. C-max of PPF was about 828.4 ng/ml and the peak conce ntration was achieved at about 2.2 hr (T-max) These results indicate that P PF is rapidly disappeared from blood due to extensive metabolism into PPFOH .