Evidence map›Paper›PMID 28214989›Full record

SynthesisJournal of pharmacokinetics and pharmacodynamics2017

Exposure-response analyses of blood pressure and heart rate changes for methylphenidate in healthy adults.

Liang Li, Yaning Wang, Ramana S Uppoor, Mehul U Mehta, Tiffany Farchione, Mitchell V Mathis, Hao Zhu

Abstract readMeta-Analysis
PubMed Publisher
In one paragraph

Synthesis in Journal of pharmacokinetics and pharmacodynamics, 2017. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 8 papers.

0numbers the graph read from it
0cells of the map it votes in
8citing 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

8 citing papers in PubMed.

  1. Article
  2. Review
  3. Article
  4. Article
  5. Review
  6. Article
  7. Article
  8. Article
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

7 authors.

Liang LiDivision of Clinical Pharmacology I, Office of Clinical Pharmacology, Center for Drug Evaluation and Research, Food and Drug Administration, Silver Spring, MD, USA.
Yaning WangDivision of Pharmacometrics, Office of Clinical Pharmacology, Center for Drug Evaluation and Research, Food and Drug Administration, Silver Spring, MD, USA.
Ramana S UppoorDivision of Clinical Pharmacology I, Office of Clinical Pharmacology, Center for Drug Evaluation and Research, Food and Drug Administration, Silver Spring, MD, USA.
Mehul U MehtaDivision of Clinical Pharmacology I, Office of Clinical Pharmacology, Center for Drug Evaluation and Research, Food and Drug Administration, Silver Spring, MD, USA.
Tiffany FarchioneDivision of Psychiatry Products, Office of Drug Evaluation I, Office of New Drugs, Center for Drug Evaluation and Research, Food and Drug Administration, Silver Spring, MD, USA.
Mitchell V MathisDivision of Psychiatry Products, Office of Drug Evaluation I, Office of New Drugs, Center for Drug Evaluation and Research, Food and Drug Administration, Silver Spring, MD, USA.
Hao ZhuDivision of Clinical Pharmacology I, Office of Clinical Pharmacology, Center for Drug Evaluation and Research, Food and Drug Administration, Silver Spring, MD, USA. hao.zhu@fda.hhs.gov.ORCID 0000-0002-3858-2048

Funding

No grant is acknowledged in the PubMed record.

6 · The paper itself

Abstract

The aim of the study was to evaluate the exposure-response (E-R) relationships of blood pressure (BP) and heart rate (HR) changes in healthy adults taking methylphenidate (MPH). Intensive time profiles of BP and HR from healthy adults in placebo and MPH treatment arms of seven clinical trials from the FDA internal database were utilized for this analysis. The analysis model contains a circadian component for placebo effect and an E-R component to describe drug effect. Internal validation was performed using goodness-of-fit plots and visual predictive check. A meta-database based on a systemic literature search was constructed and used for external validation of the developed models. We found that circadian models could quantify the time profiles of BP/HR in placebo arms. Linear models could describe the correlations between MPH concentrations, and BP/HR changes. The BP and HR changes were highly dependent on the shapes of MPH pharmacokinetic (PK) profiles without an apparent time delay. MPH has the greatest effect on HR, followed by systolic BP, and diastolic BP. Internal validation revealed that the developed models could adequately describe the circadian rhythms of HR and BP in placebo arms and the E-R relationships of MPH. External validation showed the models had good predictive capability of the literature data. In conclusion, the developed models adequately characterized the circadian rhythm and the MPH induced effects on BP and HR. The changes in BP and HR were highly correlated with MPH blood levels with no apparent delay. The time courses of BP and HR are similar to the MPH PK profiles. As a result, the immediate-release formulation may yield larger maximum BP and HR effect than the extended-release formulation under similar dose.

Indexed as

AdultAgedBlood PressureBlood Pressure DeterminationCircadian RhythmClinical Trials as TopicDelayed-Action PreparationsDose-Response Relationship, DrugFemaleHealthy VolunteersHeart RateHumansMaleMethylphenidateYoung AdultDelayed-Action PreparationsMethylphenidateAttention-deficit/hyperactivity disorder (ADHD)Diastolic blood pressure (DBP)Heart rate (HR)Methylphenidate (MPH)Modeling and simulationSystolic blood pressure (SBP)

Identifiers

PMID28214989

What OpenQuestion holds

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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.