کد مقاله | کد نشریه | سال انتشار | مقاله انگلیسی | نسخه تمام متن |
---|---|---|---|---|
5860778 | 1133239 | 2011 | 7 صفحه PDF | دانلود رایگان |
عنوان انگلیسی مقاله ISI
Toxicokinetics, including saturable protein binding, of 4-chloro-2-methyl phenoxyacetic acid (MCPA) in patients with acute poisoning
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کلمات کلیدی
tmaxLimit of reporting4-Chloro-2-methylphenoxyacetic acid (MCPA)KOCpKaIQRToxicokineticMCPA2,4-D - 2،4-D2,4-dichlorophenoxyacetic acid - 2،4-dichlorophenoxyacetic اسیدt1/2 - t1 / 2LOR - آنها4-Chloro-2-methylphenoxyacetic acid - اسید 4-کلرو-2-متیل فنسویک استclearance - ترخیص کالا از گمرکacid dissociation constant - ثابت جداسازی اسیدVolume of distribution - حجم توزیعLOD یا Limit of detection - حد تشخیصInitial concentration - غلظت اولیهinterquartile range - محدوده بین محدبlimit of detection - محدودیت تشخیصelimination rate constant - نرخ ثابت حذفDose-dependent - وابسته به دوزProtein binding - پیوند پروتئین
موضوعات مرتبط
علوم زیستی و بیوفناوری
علوم محیط زیست
بهداشت، سم شناسی و جهش زایی
پیش نمایش صفحه اول مقاله
چکیده انگلیسی
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.
ناشر
Database: Elsevier - ScienceDirect (ساینس دایرکت)
Journal: Toxicology Letters - Volume 201, Issue 3, 25 March 2011, Pages 270-276
Journal: Toxicology Letters - Volume 201, Issue 3, 25 March 2011, Pages 270-276
نویسندگان
Darren M. Roberts, Andrew H. Dawson, Lalith Senarathna, Fahim Mohamed, Ron Cheng, Geoffrey Eaglesham, Nick A. Buckley,