ArticleJournal of pharmaceutical sciences2012
On quantitative relationships between drug-like compound lipophilicity and plasma free fraction in monkey and human.
Article in Journal of pharmaceutical sciences, 2012. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 35 papers.
What it found
Each row is one number read from the abstract, on the scale the paper reported it, with its interval. Left of the dashed line favours the treatment, right favours the comparator. Under each row is the sentence it came from. New to these charts? A ten-minute tutorial.
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.
The trial behind it
Trials whose registry record cites this paper, or whose number appears in the abstract. A trial that started after this paper was published is citing it as background, not reporting it.
Neither the registry nor the abstract names a trial number. If this is a trial report, that itself is worth knowing.
Who cites it
35 citing papers in PubMed, 47 citations in OpenAlex.
- Mapping human brain fatty acid amide hydrolase activity with PET.Journal of cerebral blood flow and metabolism : official journal of the International Society of Cerebral Blood Flow and Metabolism · 2013Trial
- [European journal of nuclear medicine and molecular imaging · 2026Article
- Article
- Human plasma protein bindings of neonicotinoid insecticides and metabolites.Scientific reports · 2025Article
- A Novel Prodrug Strategy Based on Reversibly Degradable Guanidine Imides for High Oral Bioavailability and Prolonged Pharmacokinetics of Broad-Spectrum Anti-influenza Agents.ACS central science · 2024Article
- Robust Quantification of Phosphodiesterase-4D in Monkey Brain with PET andJournal of nuclear medicine : official publication, Society of Nuclear Medicine · 2024Article
- Synthesis and preclinical evaluation of [Scientific reports · 2024Article
- Precision peptide theranostics: developingTheranostics · 2024Article
- Synthesis, Structure-Activity Relationships, Radiofluorination, and Biological Evaluation of [Journal of medicinal chemistry · 2023Article
- Development of the High-Affinity Carborane-Based Cannabinoid Receptor Type 2 PET Ligand [Journal of medicinal chemistry · 2023Article
- Preliminary Assessment of the Anti-inflammatory Activity of New Structural Honokiol Analogs with a 4'-Molecules (Basel, Switzerland) · 2021Article
- PET ligands [Science translational medicine · 2020Article
- Synthesis and evaluation of two new candidate high-affinity full agonist PET radioligands for imaging 5-HTNuclear medicine and biology · 2019Article
- Design, synthesis and evaluation ofNuclear medicine and biology · 2019Article
- 3-Substituted 1,5-Diaryl-1 H-1,2,4-triazoles as Prospective PET Radioligands for Imaging Brain COX-1 in Monkey. Part 2: Selection and Evaluation of [ACS chemical neuroscience · 2018Article
- 2-(4-Methylsulfonylphenyl)pyrimidines as Prospective Radioligands for Imaging Cyclooxygenase-2 with PET-Synthesis, Triage, and Radiolabeling.Molecules (Basel, Switzerland) · 2018Article
- [Molecules (Basel, Switzerland) · 2018Article
- [Carboxyl-ChemMedChem · 2018Article
- Tactics for preclinical validation of receptor-binding radiotracers.Nuclear medicine and biology · 2017Review
- Synthesis and Preliminary PET Imaging Studies of a FAAH Radiotracer ([¹¹C]MPPO) Based on α-Ketoheterocyclic Scaffold.ACS chemical neuroscience · 2016Article
Corrections and comments
PubMed lists nothing against this paper. Absence here is not a guarantee, only a check that was made.
Authors and funding
6 authors at 2 institutions in 1 country.
Funding
Abstract
Drug interactions with plasma proteins influence their pharmacokinetics and pharmacodynamics. We aimed to test whether a strong quantitative relationship exists between plasma free fraction (f(P) ) and lipophilicity for low molecular weight nonacidic drug-like compounds. We measured the n-octanol-buffer distribution coefficients at pH 7.4 ((m) logD) of 18 diverse radiotracers (<470 Da) used for brain imaging with positron emission tomography in vivo. Lipophilicities were also computed as (c) logD with two software packages. The f(P) values for monkeys and humans were determined by ultrafiltration and transformed into m logD(pr/pl) values representing the log(10) of the within phase partition of the radiotracers between plasma proteins and remaining plasma. (m) logD(pr/pl) correlated strongly with (m) logD for human ((m) logD(pr/pl) = 0.733(m) logD-0.780, r(2) = 0.74) and monkey ((m) logD(pr/pl) = 0.780(m) logD-1.15, r(2) = 0.83), but less strongly with (c) logD. These relationships were significantly different between species (P = 0.006). Removal of eight fluorinated compounds from the datasets raised r(2) to 0.81 and 0.91 for humans and monkeys, respectively. For the tested compounds, we conclude that n-octanol-buffer (pH 7.4) distribution strongly models that between plasma proteins and remaining plasma and moreover that (m) logD accounts for over 74% of compound (m) logD(pr/pl) and is a strong determinant of f(P).
Indexed as
Identifiers
What OpenQuestion holds
Registered trials
Read under generation 80e0d062 · epoch 390. Bibliography from PubMed, PubMed Central and OpenAlex; grants from NIH RePORTER; trial links from ClinicalTrials.gov; estimates, votes and beliefs from the OpenQuestion graph.