Factors influencing naproxen metabolite interference in total bilirubin assays

Nabiha Huq Saifee1, Pratistha Ranjitkar1, Dina N Greene1

  • 1Department of Laboratory Medicine, University of Washington, 1959 NE Pacific St, Box 357110, Seattle, WA 98195, USA.

Clinical Biochemistry
|November 22, 2015
PubMed
Abstract

Insights

Naproxen metabolite O-desmethylnaproxen (ODMN) interferes with some total bilirubin (Tbil) assays due to acidic pH. The AU Jendrassik and Grof (JG) Tbil assay is reliable for measuring Tbil during naproxen overdose.

Area of Science:

  • Clinical Chemistry
  • Analytical Chemistry
  • Pharmacology

Background:

  • Naproxen metabolite O-desmethylnaproxen (ODMN) causes interference in certain total bilirubin (Tbil) assays.
  • The reasons for ODMN interference in Jendrassik and Grof (JG) Tbil assays and its absence in direct bilirubin (Dbil) assays remain unclear.

Purpose of the Study:

  • To elucidate the conditions responsible for the interference pattern of ODMN in bilirubin assays.
  • To identify reliable methods for Tbil measurement in patients taking naproxen.

Main Methods:

  • Plasma samples spiked with ODMN and naproxen were analyzed on Beckman Coulter DxC and AU instruments.
  • Absorbance spectra were recorded for ODMN with Dbil and Tbil assay reagents at varying pH levels.

Main Results:

  • ODMN caused positive interference in DxC JG Tbil assays but not in AU Tbil or Dbil assays, or DxC Dbil assays.
  • Neutralizing acidic pH in Dbil reagents enabled ODMN reaction with diazo salts.
  • Spectra showed ODMN diazo-reacted products absorb maximally between 400-560nm, with DxC JG Tbil assay's 520nm monitoring wavelength being closer to the peak than AU Tbil's 570/660nm.

Conclusions:

  • Acidic pH in diazo-based Dbil assays prevents ODMN reaction.
  • The AU JG Tbil assay is a dependable method for Tbil determination in naproxen overdose cases.

Related Concept Videos

Hepatic Drug Excretion: Influencing Factors01:16

Hepatic Drug Excretion: Influencing Factors

The biliary system of the liver, crucial for bile secretion and drug excretion, comprises intrahepatic bile ducts that merge to form the common hepatic duct. This duct, carrying hepatic bile, combines with the cystic duct, draining the gallbladder and forming the common bile duct, which empties into the duodenum. Bile, produced by hepatic cells lining the bile canaliculi, is composed primarily of water, bile salts, pigments, electrolytes, and lesser amounts of cholesterol and fatty acids. Bile...
743
Effect of Hepatic Disease on Pharmacokinetics: Pathophysiologic Assessment and Liver Function Test01:22

Effect of Hepatic Disease on Pharmacokinetics: Pathophysiologic Assessment and Liver Function Test

In clinical practice, the direct measurement of hepatic blood flow to evaluate liver function presents significant challenges due to the intricate and specialized nature of the necessary techniques. Consequently, healthcare professionals often rely on empirical estimates derived from thorough patient examinations and liver function tests to gauge liver health. Among the tools at their disposal, the Child–Pugh and MELD scoring systems stand out for their ability to categorize and assess...
256
Pharmacogenetics of Phase II Enzymes: N-acetyltransferase, Thiopurine S-methyltransferase, UDP-glucuronosyltransferase01:27

Pharmacogenetics of Phase II Enzymes: N-acetyltransferase, Thiopurine S-methyltransferase, UDP-glucuronosyltransferase

Phase II biotransformation reactions are essential for detoxifying and eliminating xenobiotics, including many pharmaceutical compounds. These reactions typically involve conjugation, the covalent attachment of polar endogenous groups such as glucuronic acid, sulfate, methyl, or acetyl moieties to functional groups introduced during Phase I metabolism. The resulting conjugates are more water-soluble, enabling efficient renal or biliary excretion.The major classes of Phase II enzymes include...
62
Factors Affecting Protein-Drug Binding: Drug Interactions01:23

Factors Affecting Protein-Drug Binding: Drug Interactions

Drug interactions are a critical aspect of pharmacology and can occur when two or more drugs compete for the same binding site. This competition can result in one drug displacing another, altering the effect of the displaced drug. Drug interactions are complex processes that rely heavily on how much of the displacer drug is present and how strongly it can bind to the same sites as the displaced drug.
Displacement interactions can have varying outcomes, ranging from toxicity to virtually...
708
Effect of Hepatic Disease on Pharmacokinetics: Dose Adjustments Due to Hepatic Impairment01:08

Effect of Hepatic Disease on Pharmacokinetics: Dose Adjustments Due to Hepatic Impairment

Hepatic impairment, characterized by decreased liver function, does not uniformly mandate adjustments in drug dosage. Whether dosage modifications are necessary depends on various factors related to the drug's metabolism and elimination pathways. If a drug is primarily excreted via the kidneys and bypasses significant hepatic processing, if it undergoes minimal metabolic transformation in the liver, or if it is volatile and primarily expelled through the lungs, dose adjustments may not be...
345
Factors Affecting Drug Biotransformation: Biological01:19

Factors Affecting Drug Biotransformation: Biological

Biological factors significantly impact drug metabolism, influencing drug clearance, efficacy, and potential toxicity.
Species differences: Variations in enzyme systems across species can cause disparities in drug metabolism. For instance, humans may metabolize certain drugs faster than rodents, altering therapeutic effects.
Strain differences: Genetic variations within a species can result in differing enzyme activity, impacting drug response and toxicity. For example, some mouse strains may...
840