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Pharmacokinetic profile of propyl paraben in humans after oral administration
Parabens are commonly used as antimicrobial preservatives in consumer products. Because of their possible endocrine-disrupting activities, their safety has become a public concern. Although pharmacokinetic studies on parabens have been conducted in animals, limited information exists on their pharmacokinetic profiles in humans. In the present study, we determined the pharmacokinetic characteristics of propyl paraben (PP) in humans following a single oral administration of 0.6 mg/kg bw of deuterium labeled-PP. We also conducted experiment with similar design but different exposure amount (2.5 mg/kg bw) to verify the validity of the model to be developed. Blood and urine were collected at several intervals over the course of 48 h to measure levels of PP and its metabolites (conjugates and hydrolysates) in 12 male volunteers. The unconjugated parent compound (free PP), glucuronide and sulfate conjugates, p-hydroxybenzoic acid, and p-hydroxyhippuric acid were measured using HPLC-MS/MS. It was found that PP was rapidly absorbed via ingestion within 2 h and quickly eliminated (terminal half-life, 2.9 h). The fraction of administered dose excreted in the urine was 0.05% for free PP, 8.6% for total PP (free + conjugates), 23.2% for p-hydroxyhippuric acid, and 7.0% for p-hydroxybenzoic acid. Utilizing this pharmacokinetic profile, we successfully constructed a multi-compartment model where the disposition of PP was well described with two compartments and that of its metabolites was explained with first-order reactions. The present pharmacokinetic model provides insights into the kinetic properties of the disposition of PP and its metabolites in humans, and it can be used for risk assessment with biomonitoring of PP. Keywords: Propylparaben, Oral exposure, Pharmacokinetics, ADME, Urinary excretion fraction
Pharmacokinetic profile of propyl paraben in humans after oral administration
Parabens are commonly used as antimicrobial preservatives in consumer products. Because of their possible endocrine-disrupting activities, their safety has become a public concern. Although pharmacokinetic studies on parabens have been conducted in animals, limited information exists on their pharmacokinetic profiles in humans. In the present study, we determined the pharmacokinetic characteristics of propyl paraben (PP) in humans following a single oral administration of 0.6 mg/kg bw of deuterium labeled-PP. We also conducted experiment with similar design but different exposure amount (2.5 mg/kg bw) to verify the validity of the model to be developed. Blood and urine were collected at several intervals over the course of 48 h to measure levels of PP and its metabolites (conjugates and hydrolysates) in 12 male volunteers. The unconjugated parent compound (free PP), glucuronide and sulfate conjugates, p-hydroxybenzoic acid, and p-hydroxyhippuric acid were measured using HPLC-MS/MS. It was found that PP was rapidly absorbed via ingestion within 2 h and quickly eliminated (terminal half-life, 2.9 h). The fraction of administered dose excreted in the urine was 0.05% for free PP, 8.6% for total PP (free + conjugates), 23.2% for p-hydroxyhippuric acid, and 7.0% for p-hydroxybenzoic acid. Utilizing this pharmacokinetic profile, we successfully constructed a multi-compartment model where the disposition of PP was well described with two compartments and that of its metabolites was explained with first-order reactions. The present pharmacokinetic model provides insights into the kinetic properties of the disposition of PP and its metabolites in humans, and it can be used for risk assessment with biomonitoring of PP. Keywords: Propylparaben, Oral exposure, Pharmacokinetics, ADME, Urinary excretion fraction
Pharmacokinetic profile of propyl paraben in humans after oral administration
Mi-Yeon Shin (author) / Chorong Shin (author) / Jeong Weon Choi (author) / Jangwoo Lee (author) / Seungho Lee (author) / Sungkyoon Kim (author)
2019
Article (Journal)
Electronic Resource
Unknown
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