Phenobarbital

10,11-carbamazepine epoxide

Fig. 8. Phenobarbital.

recommend as the first or second choice for seizure control in affluent countries. Phenobarbital is primarily metabolized by CYP2C19 and is a known inducer of most of the enzymes in the CP450 family. When serum levels are above the optimal therapeutic interval, toxic effects include decreased consciousness, slowing of heart rate, shallow breathing, and even edema and renal failure in severe overdose.

Early measurements of phenobarbital in blood were performed using GC (43) or HPLC (5). However, as with valproic acid, today, most measurements of phenobarbital in blood are made using commercial immunoassays. One early report demonstrated interference from ethotoin in measurement of phenobarbital using HPLC (5). However, as with most chromatographic methods, interferences can be easily overcome by changing experimental conditions (e.g., changing column type, mobile phase composition). There are few reported cross-reactive interferences for phenobarbital immunoassays. One report demonstrated cross-reactivity for amobarbital, butobarbital, secobarbital, and phenytoin (44). However, these interferences occurred only at concentrations that were beyond toxic levels and at "therapeutic concentrations"; these drugs did not interfere with the assay. There is one case study reported by Nordt (45) that demonstrates a possible cross-reactivity of butalbital (Fig. 9) at therapeutic concentrations, but this was not confirmed.

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