Evidence map›Paper›PMID 26649870›Full record

ArticleClinical pharmacokinetics2016

Dose Reduction of Caspofungin in Intensive Care Unit Patients with Child Pugh B Will Result in Suboptimal Exposure.

Lisa C Martial, Roger J M Brüggemann, Jeroen A Schouten, Henk J van Leeuwen, Arthur R van Zanten, Dylan W de Lange, Eline W Muilwijk, Paul E Verweij, David M Burger, Rob E Aarnoutse and 2 more

Open access · hybridAbstract read
In one paragraph

Article in Clinical pharmacokinetics, 2016. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 27 papers, 2 of them syntheses that pooled it.

0numbers the graph read from it
0cells of the map it votes in
27citing papers in PubMed, 2 pooled it
2.7field-weighted citation impact, top 10% 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

27 citing papers in PubMed, 2 syntheses or guidelines pooled it, 43 citations in OpenAlex.

  1. Pooled it
  2. Pooled it
  3. Trial
  4. Trial
  5. Low Caspofungin Exposure in Patients in Intensive Care Units.Antimicrobial agents and chemotherapy · 2017
    Trial
  6. Article
  7. Article
  8. Article
  9. Review
  10. Article
  11. Article
  12. Article
  13. Article
  14. Review
  15. [Consensus on diagnosis and treatment of invasive fungal infection in patients with severe liver disease].Zhonghua gan zang bing za zhi = Zhonghua ganzangbing zazhi = Chinese journal of hepatology · 2022
    Article
  16. Article
  17. Article
  18. Article
  19. Article
  20. Nonstationary Pharmacokinetics of Caspofungin in ICU Patients.Antimicrobial agents and chemotherapy · 2020
    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

12 authors at 7 institutions in 2 countries.

Lisa C MartialDepartment of Pharmacy, Radboud university medical center, P.O. Box 9101, 6525 HB, Nijmegen, The Netherlands.
Roger J M BrüggemannDepartment of Pharmacy, Radboud university medical center, P.O. Box 9101, 6525 HB, Nijmegen, The Netherlands. roger.bruggemann@radboudumc.nl.
Jeroen A SchoutenDepartment of Intensive Care, Canisius Wilhelmina Hospital, Nijmegen, The Netherlands.
Henk J van LeeuwenDepartment of Intensive Care, Rijnstate Hospital, Arnhem, The Netherlands.
Arthur R van ZantenDepartment of Intensive Care, Gelderse Vallei Hospital, Ede, The Netherlands.
Dylan W de LangeDepartment of Intensive Care and National Poison Information Center Utrecht, University Medical Center Utrecht, Utrecht, The Netherlands.
Eline W MuilwijkDepartment of Pharmacy, Radboud university medical center, P.O. Box 9101, 6525 HB, Nijmegen, The Netherlands.
Paul E VerweijRadboud Institute for Health Sciences, Nijmegen, The Netherlands.
David M BurgerDepartment of Pharmacy, Radboud university medical center, P.O. Box 9101, 6525 HB, Nijmegen, The Netherlands.
Rob E AarnoutseDepartment of Pharmacy, Radboud university medical center, P.O. Box 9101, 6525 HB, Nijmegen, The Netherlands.
Peter PickkersDepartment of Intensive Care, Radboud university medical center, Nijmegen, The Netherlands.
Thomas P C DorloDepartment of Pharmaceutical Biosciences, Uppsala University, Uppsala, Sweden.
Radboud University Nijmegen · NLRadboud University Medical Center · NLCanisius-Wilhelmina Ziekenhuis · NLRijnstate Hospital · NLUniversity Medical Center Utrecht · NLUtrecht University · NLZiekenhuis Gelderse Vallei · NL

Funding

No grant is acknowledged in the PubMed record.

6 · The paper itself

Abstract

BACKGROUND AND

objectivesCaspofungin is an echinocandin antifungal agent used as first-line therapy for the treatment of invasive candidiasis. The maintenance dose is adapted to body weight (BW) or liver function (Child-Pugh score B or C). We aimed to study the pharmacokinetics of caspofungin and assess pharmacokinetic target attainment for various dosing strategies.

methodsCaspofungin pharmacokinetic data from 21 intensive care unit (ICU) patients was available. A population pharmacokinetic model was developed. Various dosing regimens (loading dose/maintenance dose) were simulated: licensed regimens (I) 70/50 mg (for BW <80 kg) or 70/70 mg (for BW >80 kg); and (II) 70/35 mg (for Child-Pugh score B); and adapted regimens (III) 100/50 mg (for Child-Pugh score B); (IV) 100/70 mg; and (V) 100/100 mg. Target attainment based on a preclinical pharmacokinetic target for Candida albicans was assessed for relevant minimal inhibitory concentrations (MICs).

resultsA two-compartment model best fitted the data. Clearance was 0.55 L/h and the apparent volumes of distribution in the central and peripheral compartments were 8.9 and 5.0 L, respectively. The median area under the plasma concentration-time curve from time zero to 24 h on day 14 for regimens I-V were 105, 65, 93, 130, and 186 mg·h/L, respectively. Pharmacokinetic target attainment was 100 % (MIC 0.03 µg/mL) irrespective of dosing regimen but decreased to (I) 47 %, (II) 14 %, (III) 36 %, (IV) 69 %, and (V) 94 % for MIC 0.125 µg/mL.

conclusionThe caspofungin maintenance dose should not be reduced in non-cirrhotic ICU patients based on the Child-Pugh score if this classification is driven by hypoalbuminemia as it results in significantly lower exposure. A higher maintenance dose of 70 mg in ICU patients results in target attainment of >90 % of the ICU patients with species with an MIC of up to 0.125 µg/mL.

Indexed as

Intensive Care UnitsAdolescentAdultAgedAged, 80 and overAntifungal AgentsBody Mass IndexCandidiasisCaspofunginDose-Response Relationship, DrugEchinocandinsFemaleHumansLipopeptidesMaleMetabolic Clearance RateAntifungal AgentsCaspofunginEchinocandinsLipopeptides

Identifiers

PMID26649870
PMCPMC4875935
OpenAlexW2194401148

What OpenQuestion holds

Textmetadata
LicenceCC BY-NC
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.