Evidence map›Paper›PMID 36917704›Full record

SynthesisCPT: pharmacometrics & systems pharmacology2023

Minimal physiologically-based hybrid model of pharmacokinetics in pregnant women: Application to antenatal corticosteroids.

Wojciech Krzyzanski, Mark A Milad, Alan H Jobe, William J Jusko

Open access · goldAbstract readMeta-Analysis
In one paragraph

Synthesis in CPT: pharmacometrics & systems pharmacology, 2023. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 10 papers, 1 of them a synthesis that pooled it.

0numbers the graph read from it
0cells of the map it votes in
10citing papers in PubMed, 1 pooled it
3.8field-weighted citation impact, top 7% of its field
1 · What the graph read from it

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.

2 · The registry

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.

3 · Its place in the literature

Who cites it

10 citing papers in PubMed, 1 synthesis or guideline pooled it, 13 citations in OpenAlex.

  1. Pooled it
  2. Review
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  4. Article
  5. Review
  6. Article
  7. Article
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4 · The record

Corrections and comments

PubMed lists nothing against this paper. Absence here is not a guarantee, only a check that was made.

5 · Who and what money

Authors and funding

4 authors at 3 institutions in 1 country.

Wojciech KrzyzanskiSchool of Pharmacy and Pharmaceutical Sciences, State University of New York, University of Buffalo, Buffalo, New York, USA.ORCID 0000-0001-9773-1739
Mark A MiladMilad Pharmaceutical Consulting LLC, Plymouth, Michigan, USA.
Alan H JobeDivision of Pulmonary Biology, Cincinnati Children's Hospital Medical Center, University of Cincinnati, Cincinnati, Ohio, USA.ORCID 0000-0003-3632-4114
William J JuskoSchool of Pharmacy and Pharmaceutical Sciences, State University of New York, University of Buffalo, Buffalo, New York, USA.ORCID 0000-0003-4027-0550
New York University · USCincinnati Children's Hospital Medical Center · USVariation Reduction Solutions (United States) · US

Funding

Mechanistic Pharmacokinetics and PharmacodynamicsR35GM131800 · NIGMS · STATE UNIVERSITY OF NEW YORK AT BUFFALO · PI JUSKO, WILLIAM J. · 2019 to 2023
$2.9M
NIGMS NIH HHS R35 GM131800
6 · The paper itself

Abstract

Minimal physiologically-based pharmacokinetic (mPBPK) models are an alternative to full physiologically-based pharmacokinetic (PBPK) models as they offer reduced complexity while maintaining the physiological interpretation of key model components. Full PBPK models have been developed for pregnancy, but a mPBPK model eases the ability to perform a "top-down" meta-analysis melding all available pharmacokinetic (PK) data in the mother and fetus. Our hybrid mPBPK model consists of mPBPK models for the mother and fetus with connection by the placenta. This model was applied to describe the rich PK data of antenatal corticosteroid betamethasone (BET) jointly with the limited data for dexamethasone (DEX) in the mother and fetus. Physiologic model parameters were obtained from the literature while drug-dependent parameters were estimated by the simultaneous fitting of all available data for DEX and BET. Maternal clearances of DEX and BET confirmed the literature values, and the expected fetal-to-maternal plasma ratios ranged from 0.3 to 0.4 for both drugs. Simulations of maternal plasma concentrations for the dosing regimens of BET and DEX recommended by the World Health Organization based on our findings revealed up to 60% lower exposures than found in nonpregnant women and offers a means of devising alternative dosing regimens. Our hybrid mPBPK model and meta-analysis approach could facilitate assessment of other classes of drugs indicated for the treatment of pregnant women.

Indexed as

Models, BiologicalPregnant PeopleAdrenal Cortex HormonesBetamethasoneFemaleFetusHumansPlacentaPregnancyAdrenal Cortex HormonesBetamethasone

Identifiers

PMID36917704
PMCPMC10196440
OpenAlexW4324133577

What OpenQuestion holds

Textmetadata
LicenceCC BY
Read underepoch 390

Registered trials

None linked

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.