ArticleThe AAPS journal2020
Construction and Verification of Physiologically Based Pharmacokinetic Models for Four Drugs Majorly Cleared by Glucuronidation: Lorazepam, Oxazepam, Naloxone, and Zidovudine.
Article in The AAPS journal, 2020. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 9 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
9 citing papers in PubMed, 21 citations in OpenAlex.
- Physiologically based pharmacokinetic modeling of long-acting extended-release naltrexone in pregnant women with opioid use disorder.CPT: pharmacometrics & systems pharmacology · 2024Trial
- Cannabinoid-Induced Stereoselective Inhibition of R-S-Oxazepam Glucuronidation: Cannabinoid-Oxazepam Drug Interactions.Pharmaceutics · 2024Article
- The Activity of Members of the UDP-Glucuronosyltransferase Subfamilies UGT1A and UGT2B is Impaired in Patients with Liver Cirrhosis.Clinical pharmacokinetics · 2023Article
- Mechanistic modeling of ophthalmic, nasal, injectable, and implant generic drug products: A workshop summary report.CPT: pharmacometrics & systems pharmacology · 2023Review
- Formulation of metoclopramide HCl gastroretentive film andSaudi pharmaceutical journal : SPJ : the official publication of the Saudi Pharmaceutical Society · 2022Article
- Rapid Absorption of Naloxone from Eye Drops.Pharmaceuticals (Basel, Switzerland) · 2022Article
- Simultaneous Quantification of Propylthiouracil and ItsPharmaceuticals (Basel, Switzerland) · 2021Article
- PBPK Modeling as a Tool for Predicting and Understanding Intestinal Metabolism of Uridine 5'-Diphospho-glucuronosyltransferase Substrates.Pharmaceutics · 2021Review
- High-throughput PBTK models forExpert opinion on drug metabolism & toxicology · 2021Review
Corrections and comments
PubMed lists nothing against this paper. Absence here is not a guarantee, only a check that was made.
Authors and funding
5 authors at 2 institutions in 1 country.
Funding
No grant is acknowledged in the PubMed record.
Abstract
Physiologically based pharmacokinetic (PBPK) modeling is less well established for substrates of UDP-glucuronosyltransferases (UGT) than for cytochrome P450 (CYP) metabolized drugs and more verification of simulations is necessary to increase confidence. To address specific challenges of UGT substrates, we developed PBPK models for four drugs cleared majorly via glucuronidation (lorazepam, oxazepam, naloxone, and zidovudine). In vitro to in vivo scaling of intrinsic clearance generated with co-cultured human hepatocytes was applied for hepatic metabolism and extra-hepatic clearance was extrapolated based on relative expression of UGT isoforms in the liver, kidney, and intestine. Non-metabolic clearance and the contributions of individual UGT isoforms to glucuronidation were based on in vitro and in vivo studies taken from the literature and simulations were verified and evaluated with a broad set of clinical pharmacokinetic data. Model evaluation showed systemic clearance predictions within 1.5-fold for all drugs and all simulated parameters were within 2-fold of observed. However, during the verification step, top-down model fitting was necessary to adjust for under-prediction of zidovudine V
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.