ArticlePharmaceutical research2013
Importance of Peptide transporter 2 on the cerebrospinal fluid efflux kinetics of glycylsarcosine characterized by nonlinear mixed effects modeling.
Article in Pharmaceutical research, 2013. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 3 papers.
What it found
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The abstract states no effect estimate the extractor could read, or names no intervention and outcome on the map, so this paper lights no cell and moves no belief. It is still indexed, cited and linked below.
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Who cites it
3 citing papers in PubMed, 4 citations in OpenAlex.
- Interaction Between Sex and Organic Anion-Transporting Polypeptide 1b2 on the Pharmacokinetics of Regorafenib and Its Metabolites Regorafenib-N-Oxide and Regorafenib-Glucuronide in Mice.Clinical and translational science · 2019Article
- Semi-Mechanistic Population Pharmacokinetic Modeling of L-Histidine Disposition and Brain Uptake in Wildtype and Pht1 Null Mice.Pharmaceutical research · 2018Article
- Population pharmacokinetic modeling of cefadroxil renal transport in wild-type and Pept2 knockout mice.Xenobiotica; the fate of foreign compounds in biological systems · 2016Article
Corrections and comments
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Authors and funding
4 authors at 2 institutions in 1 country.
Funding
Abstract
purposeTo develop a population pharmacokinetic model to quantitate the distribution kinetics of glycylsarcosine (GlySar), a substrate of peptide transporter 2 (PEPT2), in blood, CSF and kidney in wild-type and PEPT2 knockout mice.
methodsA stepwise compartment modeling approach was performed to describe the concentration profiles of GlySar in blood, CSF, and kidney simultaneously using nonlinear mixed effects modeling (NONMEM). The final model was selected based on the likelihood ratio test and graphical goodness-of-fit.
resultsThe profiles of GlySar in blood, CSF, and kidney were best described by a four-compartment model. The estimated systemic elimination clearance, volume of distribution in the central and peripheral compartments were 0.236 vs 0.449 ml/min, 3.79 vs 4.75 ml, and 5.75 vs 9.18 ml for wild-type versus knockout mice. Total CSF efflux clearance was 4.3 fold higher for wild-type compared to knockout mice. NONMEM parameter estimates indicated that 77% of CSF efflux clearance was mediated by PEPT2 and the remaining 23% was mediated by the diffusional and bulk clearances.
conclusionsDue to the availability of PEPT2 knockout mice, we were able to quantitatively determine the significance of PEPT2 in the efflux kinetics of GlySar at the blood-cerebrospinal fluid barrier.
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