Porro M G, Kupferberg H J, Porter R J, Theodore W H, Newmark M E
Br J Clin Pharmacol. 1982 Aug;14(2):294-7. doi: 10.1111/j.1365-2125.1982.tb01980.x.
The interaction between primidone and phenytoin was studied in an epileptic patient treated with primidone only and primidone plus phenytoin for 3 months. Plasma and urine levels of drugs and metabolites were monitored daily by GC and GC-MS. The addition of phenytoin to the regimen increased steady-state plasma levels of phenobarbitone and phenylethylmalonamide (PEMA), metabolites of primidone, and decreased levels of primidone and unconjugated p-hydroxyphenobarbitone (p-OHPB), a metabolite of phenobarbitone. After withdrawal of phenytoin, plasma phenobarbitone and primidone levels slowly returned to previous steady-state levels, PEMA rapidly decreased to lower levels than before, and p-OHPB levels rose rapidly. Urinary excretion of primidone and its metabolites paralleled the changes in their plasma levels after the addition of phenytoin but the percentage of unconjugated p-OHPB in urine was unchanged during the course of the study. In conclusion phenytoin initially induces the conversion of primidone to PEMA and phenobarbitone, although each to a different extent, but it appears to inhibit the hydroxylation of phenobarbitone. Thus, two apparently contradictory phenomena seem to be involved in the primidone-phenytoin interaction. The net effect is an enhanced increase in plasma phenobarbitone levels.
在一名仅接受扑米酮治疗以及接受扑米酮加苯妥英治疗3个月的癫痫患者中，对扑米酮与苯妥英之间的相互作用进行了研究。通过气相色谱法（GC）和气相色谱 - 质谱联用仪（GC-MS）每日监测药物及其代谢产物的血浆和尿液水平。在治疗方案中添加苯妥英后，扑米酮的代谢产物苯巴比妥和苯乙基丙二酰胺（PEMA）的稳态血浆水平升高，扑米酮和苯巴比妥的代谢产物未结合的对羟基苯巴比妥（p-OHPB）水平降低。停用苯妥英后，血浆苯巴比妥和扑米酮水平缓慢恢复到先前的稳态水平，PEMA迅速降至比之前更低的水平，而p-OHPB水平迅速上升。添加苯妥英后，扑米酮及其代谢产物的尿排泄与它们的血浆水平变化平行，但在研究过程中尿中未结合的p-OHPB百分比没有变化。总之，苯妥英最初诱导扑米酮转化为PEMA和苯巴比妥，尽管程度不同，但它似乎抑制苯巴比妥的羟基化。因此，扑米酮 - 苯妥英相互作用似乎涉及两种明显矛盾的现象。最终结果是血浆苯巴比妥水平进一步升高。
