title: Possible false-negative results on therapeutic drug monitoring of phenytoin using a particle enhanced turbidimetric inhibition immunoassay in a patient with a high level of IgM.
abstract: : In this report, the authors described the unusual case of a patient in whom the plasma phenytoin concentration was unexpectedly not detected on a particle-enhanced turbidimetric inhibition immunoassay (PETINIA) technique, a typical immunoassay for phenytoin. The plasma concentration was measured using PETINIA and high-performance liquid chromatography in a 69-year-old male patient treated with fosphenytoin intravenously at the standard dose for 7 days. Although the plasma concentration of phenytoin was below the limit of detection (<0.5 mcg/mL) on PETINIA after the administration of fosphenytoin, the trough plasma concentration was estimated to be between 5 and 10 mg/L on high-performance liquid chromatography. When the plasma concentrations of IgM and IgG were measured using an enzyme-linked immunosorbent assay, the plasma IgG level was within the reference range, whereas the plasma IgM level was 2-3 times higher than the upper limit of the reference range. We concluded that the PETINIA method yielded a possible false-negative result regarding the phenytoin level in this patient, perhaps because of some hindrance to the measurement process by IgM. This case suggests that false-negative results should be considered when therapeutic drug monitoring reveals abnormally low values using PETINIA and that it is necessary to evaluate the plasma IgM level.
authors.affiliation: *Department of Pharmacy, Japanese Red Cross Kumamoto Hospital; †Division of Pharmacology and Therapeutics; ‡Department of Biopharmaceutics, Graduate School of Pharmaceutical Sciences, Kumamoto University; §Department of Clinical Pharmacy, Faculty of Pharmaceutical Science, Sojo University; ¶Center for Clinical Pharmaceutical Sciences; and ‖Department of Clinical Pharmacology, Faculty of Pharmaceutical Sciences, Kumamoto University, Japan.
authors.forename: Kenshiro
authors.initials: K
authors.lastname: Hirata
authors.forename: Junji
authors.initials: J
authors.lastname: Saruwatari
authors.forename: Yuhuki
authors.initials: Y
authors.lastname: Enoki
authors.forename: Kazufumi
authors.initials: K
authors.lastname: Iwata
authors.forename: Yukino
authors.initials: Y
authors.lastname: Urata
authors.forename: Keiji
authors.initials: K
authors.lastname: Aizawa
authors.forename: Kentaro
authors.initials: K
authors.lastname: Ueda
authors.forename: Takumi
authors.initials: T
authors.lastname: Shirouzono
authors.forename: Motoki
authors.initials: M
authors.lastname: Imamura
authors.forename: Hiroshi
authors.initials: H
authors.lastname: Moriuchi
authors.forename: Yu
authors.initials: Y
authors.lastname: Ishima
authors.forename: Daisuke
authors.initials: D
authors.lastname: Kadowaki
authors.forename: Hiroshi
authors.initials: H
authors.lastname: Watanabe
authors.forename: Sumio
authors.initials: S
authors.lastname: Hirata
authors.forename: Toru
authors.initials: T
authors.lastname: Maruyama
authors.forename: Eiko
authors.initials: E
authors.lastname: Fukunaga
mesh_terms: D000368:Aged; D000927:Anticonvulsants / Q000097:blood; D016903:Drug Monitoring / Q000379:methods*; D005188:False Negative Reactions; D006801:Humans; D007118:Immunoassay / Q000379:methods*; D007075:Immunoglobulin M / Q000097:blood*; D008297:Male; D009391:Nephelometry and Turbidimetry / Q000379:methods*; D010672:Phenytoin / Q000097:blood*
chemical_list: D000927:Anticonvulsants; D007075:Immunoglobulin M; D010672:Phenytoin