Evidence map›Paper›PMID 21930396›Full record

ArticleThe Journal of heart and lung transplantation : the official publication of the International Society for Heart Transplantation2011

Age and CYP3A5 genotype affect tacrolimus dosing requirements after transplant in pediatric heart recipients.

Violette Gijsen, Seema Mital, Ron H van Schaik, Offie P Soldin, Steven J Soldin, Ilse P van der Heiden, Irena Nulman, Gideon Koren, Saskia N de Wildt

Open access · greenAbstract read
PubMed Full text at PMC Publisher
In one paragraph

Article in The Journal of heart and lung transplantation : the official publication of the International Society for Heart Transplantation, 2011. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 42 papers, 2 of them syntheses that pooled it.

0numbers the graph read from it
0cells of the map it votes in
42citing papers in PubMed, 2 pooled it
5.4field-weighted citation impact, top 4% 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

42 citing papers in PubMed, 2 syntheses or guidelines pooled it, 102 citations in OpenAlex.

  1. Pooled it
  2. Guideline
  3. Trial
  4. Trial
  5. Article
  6. Article
  7. Article
  8. Article
  9. Review
  10. Article
  11. Article
  12. Review
  13. Article
  14. Review
  15. Article
  16. Article
  17. Article
  18. Review
  19. Article
  20. 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

9 authors at 3 institutions in 3 countries.

Violette GijsenIntensive Care and Department of Pediatric Surgery, Erasmus MC Sophia Children's Hospital, Rotterdam, the Netherlands.
Seema Mital
Ron H van Schaik
Offie P Soldin
Steven J Soldin
Ilse P van der Heiden
Irena Nulman
Gideon Koren
Saskia N de Wildt
Erasmus MC - Sophia Children’s Hospital · NLHospital for Sick Children · CAGeorgetown University · US

Funding

WIHS INTENSIVE PHARMACOKINETIC STUDY (IPS)M01RR023942 · NCRR · GEORGETOWN UNIVERSITY · PI FEDEROFF, HOWARD J. · 2007 to 2009
$6.9M
Hyopthyroidism Treatment in Aging and Thyroid CancerR01AG033867 · NIA · GEORGETOWN UNIVERSITY · PI BURMAN, KENNETH D, JONKLAAS, JACQUELINE · 2010 to 2014
$1.8M
NCRR NIH HHS M01 RR023942NIA NIH HHS R01 AG033867
6 · The paper itself

Abstract

backgroundTacrolimus is one of the commonly used immunosuppressive drugs for pediatric heart transplants. Large variation exists in pharmacokinetics during the direct post-transplant period, resulting in an increased risk of adverse events. Limited data are available on the interaction of age, CYP3A5 and ABCB1 genotype, and disease severity on the variation in disposition and outcome in pediatric heart transplant recipients.

methodWe studied the relationship between age and CYP3A5 and ABCB1 genotype and the Pediatric Risk of Mortality (PRISM) score on tacrolimus dose (mg/kg), steady-state trough concentrations, and concentration/dose ratio, as well as rejection and renal function for 14 days after heart transplant in children.

resultsTacrolimus was administered to 39 children (median age, 6.0 years) after transplant. A correlation was found between the age at the time of transplant and the tacrolimus dosing requirements (r(s) = -0.447, p = 0.004) and the concentration/dose ratio (r(s) = 0.351, p = 0.029). CYP3A5 expressors required median (interquartile range) higher doses of tacrolimus (0.14 [0.09] vs 0.06 [0.04] mg/kg/12 hours, p = 0.001), and had lower concentration/dose ratios (45.34 [44.54] vs 177.78 [145.38] ng/ml per mg/kg/12 hours, p < 0.0001). This relationship was not seen with the ABCB1 genotype. Age and CYP3A5 genotype predicted the tacrolimus dosing requirements as well as the concentration/dose ratio (R(2) = 0.351, p = 0.001 and R(2) = 0.521, p < 0.001). No relationship was found between any of the CYP3A5 or ABCB1 genotypes and the estimated glomerular filtration rate.

conclusionYounger age and CYP3A5 expressor genotype were independently associated with higher dosing requirements and lower tacrolimus concentration/dose ratios.

Indexed as

GenotypeAgingATP Binding Cassette Transporter, Subfamily BATP Binding Cassette Transporter, Subfamily B, Member 1ChildCytochrome P-450 CYP3ADose-Response Relationship, DrugFemaleGlomerular Filtration RateGraft RejectionHeart TransplantationHumansImmunosuppressive AgentsKidneyMaleRetrospective StudiesABCB1 protein, humanATP Binding Cassette Transporter, Subfamily BATP Binding Cassette Transporter, Subfamily B, Member 1CYP3A5 protein, humanCytochrome P-450 CYP3AImmunosuppressive AgentsTacrolimus

Identifiers

PMID21930396
PMCPMC3640375
OpenAlexW2049662448

What Socratic holds

Textmetadata
LicenceTDM
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 Socratic graph.