Possible Interaction: Caffeine and Phenobarbital

“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 of ….03 mmol/kg for the induction of seizures), produced a significant reduction in the anticonvulsant effects of carbamazepine, phenobarbital , phenytoin, and valproate against maximal …-induced seizures in mice.”

“In contrast, caffeine alone reduced proliferative capacity and expression of the neuronal markers DCX and NeuN … neurotrophins and neuronal transcription factors at 6 and 12 h. These results indicate that administration of phenobarbital during the vulnerable phase of brain development negatively … prevented in part by co-administration of caffeine.”

“Brains examined at … last injection of phenobarbital showed a drastic increase of … attenuated by co-treatment with caffeine at 6 and 24 h but not at 12 h. Phenobarbital also increased protein levels of … cleaved caspase-3, which was reduced by caffeine co-administration at all time points investigated.”

“We hypothesized that caffeine may counteract the proapoptotic effects of phenobarbital in newborn rats.”

“These DNAs also showed a 2–3‐fold synergistic effect of caffeine and PB but not of caffeine and DDT.”

“ 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.”

“ Phenobarbital (an inducer of CYP2B and other CYPs and a CYP2C11 inhibitor) moderately stimulated the metabolism of caffeine , but practically did not affect 7-N-demethylation.”

“Increases in serum TSH levels with PB or ID were also further enhanced in combination with caffeine.”

“Our results clearly indicate that dietary caffeine at a high dose of 1,500 ppm interacts with ID, but neither SDM nor PB, to promote rat thyroid carcinogenesis although the combined caffeine + PB treatment somewhat affected thyroid weights as well as thyroid hormone levels.”

“The caffeine, PB, SDM, and ID treatments significantly (p < 0.05 or 0.01) increased the relative thyroid weights, and the increases with PB or ID were further (p < 0.05 or 0.01) enhanced in combination with caffeine.”

“Severe liver damage induced by cotreatment with CF and AA was further, markedly enhanced by phenobarbital pretreatment (80 mg/kg, i.p.,”

“Interaction with CAF (200 mg/kg, ip) abolished the seizure protection by DPH and DZP, reduced that by PB to 20%, while the protective effect of SV was unchanged.”