Population Pharmacokinetics of Exogenous Biotin and the Relationship Between Biotin Serum Levels and In Vitro Immunoassay Interference

Abstract

Aim: Biotin in human serum is a potential interfering factor for streptavidin-biotin-based assays. We aimed to evaluate the effective half-life of biotin and biotin metabolites, and establish a pharmacokinetic (PK) model to simulate the time taken for the biotin concentration to fall below a series of thresholds. Materials & methods: PK properties of biotin (5, 10 and 20 mg daily) were evaluated in healthy participants. Biotin serum concentrations were simulated for high-dose regimens (1 mg daily to 300 mg q.i.d.) using a population PK model. Results: Washout periods required for biotin concentrations to reach thresholds ranging from 10 to 100 ng/ml were successfully simulated. Conclusion: Our simulations provide valuable guidance on biotin washout periods necessary to avoid false assay results. Immunoassays that allow rapid measurement of analytes can be vital for the correct diagnosis of a broad range of diseases [1]. The interaction of streptavidin and biotin has been utilized for the development of robust and highly sensitive immunoassays by many manufacturers (Abbott, Beckman Coulter, Ortho Clinical Diagnostics, Roche Diagnostics, Siemens Healthcare Diagnostics and others). Biotin, a water-soluble vitamin, is a small and stable molecule that can be conjugated to many proteins without significantly affecting their biological activity; this interaction is the strongest known noncovalent binding between a protein and a ligand [2].Exogenous biotin has the potential to interfere with streptavidin-biotin-based assay results. The impact of interference on test results can be the generation of falsely high values, obtained when using a competitive assay design, whereby an excess of biotin in the specimen competes with biotinylated analog for binding sites on streptavidin. Alternatively, when using a sandwich assay design, an excess of biotin in the specimen can displace biotinylated antibodies, which can generate falsely low values [3]. Reports of biotin interference leading to incorrect biochemical diagnoses in both adults and children have been published previously, along with warnings to clinicians and pathologists to interpret unexpected assay results with caution and consider the potential effect of biotin interference before making a diagnosis [4][5][6][7].The normal serum concentration of biotin is very low; published average values range from below 0.1 to 0.8 ng/ml [8,9]. The adequate daily intake of biotin is 30 μg/day [10] and biotin deficiency is rare as the majority of diets contain enough biotin for this to be reached. However, biotin is increasingly being marketed as a lifestyle supplement which is claimed to strengthen hair and nails, despite no scientific confirmation of these benefits [11]. The unregulated, over-the-counter (OTC) product is available in doses ranging from 50 μg found in multivitamin

Biotin and high-sensitivity cardiac troponin T assay

“…In the last decade, very high-doses of biotin (300 mg/day) have been shown to have a beneficial effect in patients suffering from progressive multiple sclerosis ( 4 ). Recently, interference removal protocols have been proposed to eliminate biotin in samples ( 5 , 6 ). Such protocols using pre-incubation with streptavidin-coated magnetic particles contained in Elecsys® immunoassay kits are easy to implement in laboratory workflow.…”

“…Such protocols using pre-incubation with streptavidin-coated magnetic particles contained in Elecsys® immunoassay kits are easy to implement in laboratory workflow. Studies conducted so far recommend an incubation time of neutralization protocol from 45 minutes to 1 hour which can be a concern in terms of turnaround times for an emergency biomarker ( 5 , 6 ). At Rouen University Hospital, we perform approximately 50,000 hs-cTnT assays each year and up to 40% are for the emergency department.…”

Biotin interference in TSH, FT4, and FT3 assays based on the LOCI technology: Identifying interference by dilution

“…Ali et al studied biotin interference in vitro in various biotin‐based immunoassays on Vitros 5600 analyzer and observed that biotin at 6.25 ng/mL affected TSH assay causing more than 20% negative bias. Serum biotin level after taking 5 mg supplement/day varied from 10 to 73 ng/mL . Therefore, even taking 5 mg biotin, TSH measurement using Vitros 5600 analyzer may be affected.…”

“…In general, serum biotin levels in individuals taking no biotin supplement vary from 0.4 to 1.2 ng/mL . Grimsey et al studied serum biotin levels after volunteers consumed 5, 10, or 20 mg biotin and reported that serum biotin levels after taking 5 mg supplement/d varied from 10 to 73 ng/mL. However, after taking 20 mg biotin per day the observed serum biotin levels ranged from 80 to 355 ng/mL.…”

Chemistry of Biotin–Streptavidin and the Growing Concern of an Emerging Biotin Interference in Clinical Immunoassays

“…It is rapidly absorbed with a serum half-life of 15 h and only reaches a steady state after 3 days. 21 Several other studies unravel a washout period up to 73 h for multiple sclerosis patients on 300 mg/day biotin doses. Therefore, there is insufficient evidence to support recommendations for safe testing in patients, taking high levels of biotin on a daily basis.…”