Toxicokinetics, including saturable protein binding, of 4-chloro-2-methyl phenoxyacetic acid (MCPA) in patients with acute poisoning

Roberts, Darren M., Dawson, Andrew H., Senarathna, Lalith, Mohamed, Fahim, Cheng, Ron, Eaglesham, Geoffrey and Buckley, Nick A. (2011) Toxicokinetics, including saturable protein binding, of 4-chloro-2-methyl phenoxyacetic acid (MCPA) in patients with acute poisoning. Toxicology Letters, 201 3: 270-276. doi:10.1016/j.toxlet.2011.01.011


Author Roberts, Darren M.
Dawson, Andrew H.
Senarathna, Lalith
Mohamed, Fahim
Cheng, Ron
Eaglesham, Geoffrey
Buckley, Nick A.
Title Toxicokinetics, including saturable protein binding, of 4-chloro-2-methyl phenoxyacetic acid (MCPA) in patients with acute poisoning
Journal name Toxicology Letters   Check publisher's open access policy
ISSN 0378-4274
1879-3169
Publication date 2011-03-25
Sub-type Article (original research)
DOI 10.1016/j.toxlet.2011.01.011
Open Access Status Not Open Access
Volume 201
Issue 3
Start page 270
End page 276
Total pages 7
Place of publication Shannon, Co. Clare, Ireland
Publisher Elsevier
Abstract Human data on protein binding and dose-dependent changes in toxicokinetics for MCPA are very limited. 128 blood samples were obtained in 49 patients with acute MCPA poisoning and total and unbound concentrations of MCPA were determined. The Scatchard plot was biphasic suggesting protein binding to two sites. The free MCPA concentration increased when the total concentration exceeded 239. mg/L (95% confidence interval 198-274. mg/L). Nonlinear regression using a two-site binding hyperbola model estimated saturation of the high affinity binding site at 115. mg/L (95%CI 0-304). Further analyses using global fitting of serial data and adjusting for the concentration of albumin predicted similar concentrations for saturable binding (184. mg/L and 167. mg/L, respectively) without narrowing the 95%CI. In 25 patients, the plasma concentration-time curves for both bound and unbound MCPA were approximately log-linear which may suggest first order elimination, although sampling was infrequent so zero order elimination cannot be excluded. Using a cut-off concentration of 200. mg/L, the half-life of MCPA at higher concentrations was 25.5. h (95%CI 15.0-83.0. h; n = 16 patients) compared to 16.8. h (95%CI 13.6-22.2. h; n = 10 patients) at lower concentrations. MCPA is subject to saturable protein binding but the influence on half-life appears marginal.
Keyword 4-Chloro-2-methylphenoxyacetic acid (MCPA)
Chlorophenoxy herbicide
Dose-dependent
Protein binding
Q-Index Code C1
Q-Index Status Provisional Code
Institutional Status UQ

Document type: Journal Article
Sub-type: Article (original research)
Collection: School of Medicine Publications
 
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