Evidence map›Paper›PMID 31169344›Full record

ArticleClinical and translational science2019

A Proposal of Conducting Bioequivalence Trials with Gastric pH Modulators for Two Oral Formulations Demonstrating Different Dissolution Profiles at Elevated pH.

Hao Zhu, Xiaomei Chen, Mariam Ahmed, Yaning Wang, Qi Liu, Ramana S Uppoor, Colleen Kuemmel, Mehul Mehta

Abstract read
PubMed Full text at PMC Publisher
In one paragraph

Article in Clinical and translational science, 2019. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 1 paper.

0numbers the graph read from it
0cells of the map it votes in
1citing papers in PubMed
–field-weighted citation impact
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

1 citing paper in PubMed.

  1. Trial
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

8 authors.

Hao ZhuOffice of Clinical Pharmacology, Office of Translational Science, Center for Drug Evaluation and Research, US Food and Drug Administration, Silver Spring, Maryland, USA.
Xiaomei ChenOffice of Clinical Pharmacology, Office of Translational Science, Center for Drug Evaluation and Research, US Food and Drug Administration, Silver Spring, Maryland, USA.
Mariam AhmedOffice of Clinical Pharmacology, Office of Translational Science, Center for Drug Evaluation and Research, US Food and Drug Administration, Silver Spring, Maryland, USA.
Yaning WangOffice of Clinical Pharmacology, Office of Translational Science, Center for Drug Evaluation and Research, US Food and Drug Administration, Silver Spring, Maryland, USA.
Qi LiuOffice of Clinical Pharmacology, Office of Translational Science, Center for Drug Evaluation and Research, US Food and Drug Administration, Silver Spring, Maryland, USA.
Ramana S UppoorOffice of Clinical Pharmacology, Office of Translational Science, Center for Drug Evaluation and Research, US Food and Drug Administration, Silver Spring, Maryland, USA.
Colleen KuemmelOffice of Clinical Pharmacology, Office of Translational Science, Center for Drug Evaluation and Research, US Food and Drug Administration, Silver Spring, Maryland, USA.
Mehul MehtaOffice of Clinical Pharmacology, Office of Translational Science, Center for Drug Evaluation and Research, US Food and Drug Administration, Silver Spring, Maryland, USA.

Funding

No grant is acknowledged in the PubMed record.

6 · The paper itself

Abstract

In this paper, a special case for bioequivalence evaluation of oral formulations is discussed. Drug formulations with different forms of active moieties (e.g., free base and salt) may yield different dissolution characteristics and, thus, differ in absorption at elevated gastric pH. However, routine bioequivalence trials using subjects with normal gastric pH (i.e., ~ 1) may fail to identify these differences because dissolution/absorption profiles of the two formulations at normal gastric pH are similar. In the case of palbociclib, it is confirmedthat the free base and salt formulations showed different absorption in patients with different gastric pH. Significant reduction in drug absorption was observed only in patients with elevated gastric pH using free base formulation. The discovery that the free base had significantly reduced absorption hinged on the inclusion of enough patients with elevated gastric pH to detect a difference in a bioequivalence trial. This raises a concern, as demonstrated through simulation, that dissolution/absorption differences in other formulations could be missed in routine bioequivalence trials. Aside from differences in active pharmaceutical ingredients (APIs), other factors, such as changes in excipients or manufacturing methods, may also lead to exposure differences between formulations at elevated gastric pH. For formulations containing different forms of the same active moiety or the same API and showing different dissolution profiles at elevated pH (i.e., pH ~ 4-6.8), evaluation of bioequivalence with gastric pH modulators (e.g., a H

Indexed as

Drug LiberationEquivalence Trials as TopicResearch DesignAdministration, OralAntacidsArea Under CurveChemistry, PharmaceuticalComputer SimulationDrug CompoundingExcipientsGastric AcidGastrointestinal AbsorptionHumansHydrogen-Ion ConcentrationModels, BiologicalPiperazinesAntacidsExcipientspalbociclibPiperazinesPrasugrel HydrochloridePyridines

Identifiers

PMID31169344
PMCPMC6853150

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Registered trials

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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.