INTRODUCTION: Phenytoin is a drug used for the treatment of different types of seizures. Its variable pharmacokinetics, mainly a consequence of variable bioavailability, saturable protein binding and saturable hepatic metabolism, predisposes the drug to therapeutic drug monitoring. Several methods to analyze the drug in serum exist with immunoassays being the method of choice for routine measurements. Immunoassays are specific and sensitive, but cross-reactivity, possibly leading to erroneous serum levels, is a concern. We report a patient with falsely undetectable phenytoin serum levels. CASE REPORT: This 73-year old woman was treated with intravenous phenytoin due to epilepsia partialis continua in the context of a bilateral cerebrovascular insult. Anamnestically, a chronic lymphatic leukemia was known. In this patient, serum phenytoin levels became only detectable by the particle enhanced turbidimetric inhibition immunoassay used after precipitation of serum proteins. Protein electrophoresis revealed a monoclonal immunoglobulin, identified as IgMlambda. With other methods such as HPLC and fluorescence depolarization immunoassay, phenytoin was detectable. CONCLUSION: We propose interference between the monoclonal IgMlambda and/or other serum proteins and the particle-enhanced turbidimetric inhibition immunoassay, rendering phenytoin falsely undetectable in samples of this patient. In such patients, alternative methods such as HPLC should be used to prevent dosage errors.
INTRODUCTION:Phenytoin is a drug used for the treatment of different types of seizures. Its variable pharmacokinetics, mainly a consequence of variable bioavailability, saturable protein binding and saturable hepatic metabolism, predisposes the drug to therapeutic drug monitoring. Several methods to analyze the drug in serum exist with immunoassays being the method of choice for routine measurements. Immunoassays are specific and sensitive, but cross-reactivity, possibly leading to erroneous serum levels, is a concern. We report a patient with falsely undetectable phenytoin serum levels. CASE REPORT: This 73-year old woman was treated with intravenous phenytoin due to epilepsia partialis continua in the context of a bilateral cerebrovascular insult. Anamnestically, a chronic lymphatic leukemia was known. In this patient, serum phenytoin levels became only detectable by the particle enhanced turbidimetric inhibition immunoassay used after precipitation of serum proteins. Protein electrophoresis revealed a monoclonal immunoglobulin, identified as IgMlambda. With other methods such as HPLC and fluorescence depolarization immunoassay, phenytoin was detectable. CONCLUSION: We propose interference between the monoclonal IgMlambda and/or other serum proteins and the particle-enhanced turbidimetric inhibition immunoassay, rendering phenytoin falsely undetectable in samples of this patient. In such patients, alternative methods such as HPLC should be used to prevent dosage errors.