Possible Interaction: Caffeine and Carbamazepine

“Also, the plasma t 1/2 (of carbamazepine was prolonged by two folds and bioavailability reduced by about 32% in presence of caffeine.”

“Both the serum concentration of sodium valproate and pharmacokinetic parameters remained unaltered, as against significant reduction in plasma concentration and area under the concentration curve of carbamazepine following the coadministration of caffeine.”

“Interestingly, animal data have demonstrated that caffeine , at doses far below its convulsive potential, diminishes the protective effects of conventional antiepileptic drugs (AEDs-- carbamazepine , phenobarbital, phenytoin, valproate) and the newer AED, topiramate against electroconvulsions in mice.”

“ Acute caffeine , in doses far below its convulsive potential (almost 10-20 fold lower than the ED50 of the methylxanthine … 2.03 mmol/kg for the induction of seizures), produced a significant reduction in the anticonvulsant effects of carbamazepine , phenobarbital, phenytoin, and valproate against … electroshock-induced seizures in mice.”

“Concomitant use of caffeine and carbamazepine may interfere with MEGX and bupivacaine determination, respectively.”

“ Caffeine has been reported to be proconvulsant and to reduce the anticonvulsant efficacy of a variety of antiepileptic drugs ( carbamazepine , phenobarbital, phenytoin, valproate and topiramate) in animal models of epilepsy and to increase seizure frequency in patients with epilepsy.”

“Coadministration of caffeine (250-1000 nmol/paw), a nonselective adenosine-receptor antagonist, as well as DPCPX (10-30 nmol/paw), a selective adenosine A(1)-receptor antagonist, with carbamazepine , significantly depressed its anti-hyperalgesic effect.”

“A significant reduction of the protective efficacy of CBZ was observed after chronic CAFF treatment (in a dose of 11.55 mg/kg), while a single dose and a 3-day treatment did not alter the action of CBZ.”

“A strong impairment of the anticon-vulsant action of CBZ and DPH was observed when a challenge dose of CAFF was injected following either 24 or 72 h injection-free time.”

“Moreover the ED50 values for both, CBZ and DPH, evaluated 24 h after a 14-day treatment with CAFF (in doses of 23.1 and 46.2 mg/kg, respectively), were significantly elevated compared to respective control groups.”

“In doses of 0.238 and 0.476 mmol/kg, caffeine also diminished the efficacy of CBZ and VPA, and at the highest dose tested the methylxanthine elevated the respective ED50s from 13 to 20.5 mg/kg and from 270 to 420 mg/kg.”

“At the highest tolerated doses, aminophylline (150 mg/kg, ip) and caffeine (250 mg/kg, ip) produced antagonism of CBZ protection against pentylenetetrazole seizures.”

“Although regional distribution of [3H]CHA and [3H]forskolin binding sites differed in some areas, chronic CBZ as well as chronic caffeine upregulated both of them.”