Trial reportClinical pharmacology and therapeutics2016
Batch-to-batch pharmacokinetic variability confounds current bioequivalence regulations: A dry powder inhaler randomized clinical trial.
Trial report in Clinical pharmacology and therapeutics, 2016. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 17 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
17 citing papers in PubMed.
- Pharmacokinetic Models for Inhaled Fluticasone Propionate and Salmeterol Xinafoate to Quantify Batch-to-Batch Variability.The AAPS journal · 2024Trial
- Equivalent Systemic Exposure to Fluticasone Propionate/Salmeterol Following Single Inhaled Doses from Advair Diskus and Wixela Inhub: Results of Three Pharmacokinetic Bioequivalence Studies.Journal of aerosol medicine and pulmonary drug delivery · 2020Trial
- Particle size and gastrointestinal absorption influence tiotropium pharmacokinetics: a pilot bioequivalence study of PUR0200 and Spiriva HandiHaler.British journal of clinical pharmacology · 2019Trial
- Therapeutic Differences in 24-h Ambulatory Blood Pressures in Patients Switched Between Bioequivalent Nifedipine Osmotic Systems With Differing Delivery Technologies.Clinical and translational science · 2017Trial
- Between-Batch Pharmacokinetic Variability Inflates Type I Error Rate in Conventional Bioequivalence Trials: A Randomized Advair Diskus Clinical Trial.Clinical pharmacology and therapeutics · 2017Trial
- Efficient Cytosolic Delivery of siRNA Using Lyophilized and Reconstituted Polymer-siRNA Polyplexes.Pharmaceutical research · 2025Article
- Identification of Spectral Fingerprints in Different Batches of Antimalarial Herbal Drugs Using Laser-Induced Autofluorescence and Chemometric Techniques.Journal of fluorescence · 2025Article
- Exploration of the potential impact of batch-to-batch variability on the establishment of pharmacokinetic bioequivalence for inhalation powder drug products.CPT: pharmacometrics & systems pharmacology · 2025Article
- Microstructural Characterization of Dry Powder Inhaler Formulations Using Orthogonal Analytical Techniques.Pharmaceutical research · 2024Article
- Predicting Optimal Antimalarial Drug Combinations from a Standardized Plasmodium falciparum Humanized Mouse Model.Antimicrobial agents and chemotherapy · 2023Article
- iBCS: 2. Mechanistic Modeling of Pulmonary Availability of Inhaled Drugs versus Critical Product Attributes.Molecular pharmaceutics · 2022Article
- Performance of Multiple-Batch Approaches to Pharmacokinetic Bioequivalence Testing for Orally Inhaled Drug Products with Batch-to-Batch Variability.AAPS PharmSciTech · 2021Article
- Between-Batch Bioequivalence (BBE): a Statistical Test to Evaluate In Vitro Bioequivalence Considering the Between-Batch Variability.The AAPS journal · 2020Article
- Sample size determination in bioequivalence studies using statistical assurance.British journal of clinical pharmacology · 2019Article
- Biological Obstacles for IdentifyingPharmaceutics · 2019Review
- Evaluating the Feasibility of Use of a Foreign Reference Product for Generic Drug Applications: A Retrospective Pilot Study.European journal of drug metabolism and pharmacokinetics · 2017Article
- Clinical Pharmacology & Therapeutics: Past, Present, and Future.Clinical pharmacology and therapeutics · 2017Article
Corrections and comments
PubMed lists nothing against this paper. Absence here is not a guarantee, only a check that was made.
Authors and funding
4 authors.
Funding
No grant is acknowledged in the PubMed record.
Abstract
Current pharmacokinetic (PK) bioequivalence guidelines do not account for batch-to-batch variability in study design or analysis. Here we evaluate the magnitude of batch-to-batch PK variability for Advair Diskus 100/50. Single doses of fluticasone propionate and salmeterol combinations were administered by oral inhalation to healthy subjects in a randomized clinical crossover study comparing three different batches purchased from the market, with one batch replicated across two treatment periods. All pairwise comparisons between different batches failed the PK bioequivalence statistical test, demonstrating substantial PK differences between batches that were large enough to demonstrate bio-inequivalence in some cases. In contrast, between-replicate PK bioequivalence was demonstrated for the replicated batch. Between-batch variance was ∼40-70% of the estimated residual error. This large additional source of variability necessitates re-evaluation of bioequivalence assessment criteria to yield a result that is both generalizable and consistent with the principles of type I and type II error rate control.
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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.