Evidence that 5′-Cytidinediphosphocholine Can Affect Brain Phospholipid Composition by Increasing Choline and Cytidine Plasma Levels

We examined the effects of orally administered 5'-cytidinediphosphocholine (CDP-choline) on arterial plasma choline and cytidine levels and on brain phospho- lipid composition in rats . Animals receiving a single oral dose of 100, 250, or 500 mg/kg showed peak plasma choline levels 6-8 h after drug administration (from 12 1 to 17 ± 2, 19 ± 2, and 24 ± 2 pM, respectively) . The area under the plasma choline curve at >14 IiM,i.e., at a concentration that induces a net influx of choline into the brain, was significantly correlated with CDP-choline dose .In rats receiving 500 mg/kg this area was 2 .3 times that of animals consuming 250 mg/kg, which in turn was 1 .8 times that of rats receiving 100 mg/kg . Plasma cyti- dine concentrations increased 5 .4, 6 .5, and 15 .1 times baseline levels, respectively, 8 h after each of the three doses . When the oral CDP-choline treatment was pro- longed for 42 and 90 days, brain phosphatidylcholine concentrations increased significantly (by 22-25% ; p < 0 .05) in rats consuming 500 mg/kg/day . Brain phos- phatidylethanolamine and phosphatidylserine concentra- tions also increased significantly under some experi- mental conditions ; levels of other phospholipids were