Phenytoin, labelled

Homogeneous electrochemical enzyme immunoassays for both phenytoin and digoxin have been developed. In both cases the label was glucose-6-phosphate dehydrogenase, which catalyzes the reduction of NAD to NADH. The NADH produced was detected by LCEC at a carbon paste electrode. 

An immunosensor based on a competitive fluorescence energy-transfer immunoassay was reported by Anderson 105) for the measurement of phenytoin. Texas red-labeled antibody was incubated with a phenytoin derivative. On displacement of the derivative by the antigen, the change in the fluorescence signal was recorded. Detection limits approached 5 /iM with response times ranging from 5 to 30 min. 

A pediatric patient was presented to the emergency room (ER) experiencing seizures for which 150-mg Cerebyx (fosphenytoin anticonvulsant) IV was ordered. The pharmacy technician took the call for Cerebyx and delivered three 10-mL vials of Cerebyx 50-mg PE (phenytoin sodium equivalents) per mL to the ER as a floor stock transaction. A nurse misread the 50-mg PE/mL on the 10-mL container label, making the assumption that the entire vial contained 50 mg PE. The contents of all three vials were prepared for administration. Instead of 150 mg PE, the patient was administered ten times the intended dose, or 1,500 mg PE. The patient later died. The ER staff only discovered the error after the patient s blood phenytoin levels were returned from the laboratory. 

Serious medication errors, including some leading to death, have resulted from the interpretation of the Cerebyx product labeling. The terminology on the label, which previously indicated the concentration as being 50 mg of phenytoin equivalents (PE) per milliliter, was misinterpreted as the total number of PEs per vial. Furthermore, health professionals were reportedly confused by the expression phenytoin equivalents, a prodrug concept introduced for this product. As a result, massive fosphenytoin overdoses were mistakenly administered. 

IB (tocainide, lidocaine, phenytoin, mexiletine) - Depress phase 0 slightly and may shorten the action potential duration. Although arrhythmia is not a labeled indication for phenytoin, it is commonly used in treatment of digitalis-induced arrhythmias. 

Baclofen, labeled as a skeletal muscle relaxant binds to GABA receptors and depresses excitation. It is also useful in the treatment of paroxysms of trigeminal neuralgia. Baclofen is effective in patients with carbamazepine-resistant pain and has been used successfully to relieve attacks in patients previously unresponsive to carbamazepine or phenytoin. 

If a drug is a substrate of CYP3A, coadministration with St. John s wort, a CYP3A inducer, can decrease the systemic exposure and effectiveness. St. John s wort may be listed in the labeling along with other known inducers, such as rifampin, rifabutin, rifapentin, dexamethasone, phenytoin, carbamazepine, or phenobarbital, as possibly decreasing plasma levels. 

E249 Danielson, S.J., Olyslager, R., Hosimer, P.C. and Sundberg, M.W. (1986). Alteration of the performance of a multilayer enzyme immunoassay for phenytoin by structural modification of the enzyme label. Clin. Chem. 32, 1066, Abstr. 80. 

The product labeling states that the simultaneous administration of sucralfate may reduce the bioavailability of certain agents (e.g.. tetracycline, phenytoin. digoxin. orcimelidine). It further recommends restoration of bioavailability by separating administration of the.se agents from that of sucralfate by 2 hours. Presumably, sucralfate binds these agents in the GI tract. 

TBG tests that use labeled T4 have also been developed. In one commercial assay, a two-site IRMA or sandwich assay is used. TBG antibody bound to glass particles is added in excess to the patient specimen and binds virtually aU the endogenous TBG present. I-T4 is then added it binds to the TBG, forming an anti-TBG-TBG- I T4 sandwich. After a short 15-minute incubation period at room temperature, the precipitate is collected by centrifugation and its radioactivity is counted. Test values are interpreted from a calibration curve run simultaneously with the patient specimens. Unlike the typical RIA procedure, radioactivity in this IRMA method is directly proportional to the amount of TBG present in the specimen. Patients with molecular variants of TBG may have discordant results, but the assay is not affected by excess thyroxine or phenytoin. ... 

This technique may be used in two distinct ways. The drug may be labeled at a specific site(s) and the mass spectra of metabolites derived from the labeled compound compared with those obtained from the unlabeled drug. Recent examples of this application include reports on the metabolism of oxybutynin,tocainide, and ketamine. Alternatively, a heavy isotope (usually H) is introduced into the metabolite of interest by reaction with a labeled derivatizing reagent. For example, perdeutero-methylation results in a mass difference of 3 daltons between labeled and unlabeled derivatives per methyl group. Structures of metabolites obtained from caffeine and phenytoin have been confirmed by this technique. Tri(deuteromethyl)silylation has been employed in the identification of metabolites of carbamazepine and afloqualone. ... 

Fosphenytoin is a phosphate ester of phenytoin and labeled as 100% phenytoin acid equivalents (PE) and can be safely mixed with all diluents. A maximum infusion rate of 150 mg/min is recommended. 

Fluorescence Phenytoin (serum) Competitive binding of fluorescein-labeled and unlabeled phenytoin with a phenytoin antibody gel filtration... 

At r = 6 min, 5 p,L of serum were injected. As it flowed through the column, free phenytoin displaced some fluores-cently labeled phenytoin from the silica. Fluorescence was measured at 820 nm with laser excitation at 785 nm. 

A Comparison of Serum Phenytoin Determination by the Substrate-Labeled Fluorescence Immunoassay with Gas Chromatography, Liquid Chromatography, Radioimmunoassay and "EMIT ... 

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