Evidence map›Paper›PMID 22083471›Full record

Trial reportAntimicrobial agents and chemotherapy2012

Population pharmacokinetics of liposomal amphotericin B and caspofungin in allogeneic hematopoietic stem cell recipients.

Gudrun Würthwein, Charlotte Young, Claudia Lanvers-Kaminsky, Georg Hempel, Mirjam N Trame, Rainer Schwerdtfeger, Helmut Ostermann, Werner J Heinz, Oliver A Cornely, Hedwig Kolve and 3 more

Abstract readClinical Trial, Phase IIRandomized Controlled Trial
In one paragraph

Trial report in Antimicrobial agents and chemotherapy, 2012. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 27 papers, 1 of them a synthesis that pooled it.

0numbers the graph read from it
0cells of the map it votes in
27citing papers in PubMed, 1 pooled it
–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

27 citing papers in PubMed, 1 synthesis or guideline pooled it.

  1. Pooled it
  2. Fixed Dosing of Liposomal Amphotericin B in Morbidly Obese Individuals.Clinical infectious diseases : an official publication of the Infectious Diseases Society of America · 2020
    Trial
  3. Trial
  4. Low Caspofungin Exposure in Patients in Intensive Care Units.Antimicrobial agents and chemotherapy · 2017
    Trial
  5. Trial
  6. Trial
  7. Trial
  8. Article
  9. Review
  10. Article
  11. Liposomal amphotericin B-the past.The Journal of antimicrobial chemotherapy · 2022
    Article
  12. Postantifungal Effect of Antifungal Drugs againstJournal of fungi (Basel, Switzerland) · 2022
    Review
  13. Article
  14. Article
  15. Article
  16. Article
  17. Article
  18. Pharmacology of Liposomal Amphotericin B: An Introduction to Preclinical and Clinical Advances for Treatment of Life-threatening Invasive Fungal Infections.Clinical infectious diseases : an official publication of the Infectious Diseases Society of America · 2019
    Article
  19. Clinical Pharmacokinetics, Pharmacodynamics, Safety and Efficacy of Liposomal Amphotericin B.Clinical infectious diseases : an official publication of the Infectious Diseases Society of America · 2019
    Review
  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

13 authors.

Gudrun WürthweinCentre for Clinical Trials Muenster, University Hospital Muenster, Muenster, Federal Republic of Germany.
Charlotte Young
Claudia Lanvers-Kaminsky
Georg Hempel
Mirjam N Trame
Rainer Schwerdtfeger
Helmut Ostermann
Werner J Heinz
Oliver A Cornely
Hedwig Kolve
Joachim Boos
Gerda Silling
Andreas H Groll

Funding

No grant is acknowledged in the PubMed record.

6 · The paper itself

Abstract

Liposomal amphotericin B (LAMB) and caspofungin (CAS) are important antifungal agents in allogeneic hematopoietic stem cell transplant (aHSCT) recipients. Little is known, however, about the pharmacokinetics (PK) of both agents and their combination in this population. The PK of LAMB and CAS and the potential for PK interactions between both agents were investigated within a risk-stratified, randomized phase II clinical trial in 53 adult aHSCT recipients with granulocytopenia and refractory fever. Patients received either LAMB (n = 17; 3 mg/kg once a day [QD]), CAS (n = 19; 50 mg QD; day 1, 70 mg), or the combination of both (CAS-LAMB; n = 17) for a median duration of 10 to 13 days (range, 4 to 28 days) until defervescence and granulocyte recovery. PK sampling was performed on days 1 and 4. Drug concentrations in plasma (LAMB, 405 samples; CAS, 458 samples) were quantified by high-pressure liquid chromatography and were analyzed using population pharmacokinetic modeling. CAS concentration data best fitted a two-compartment model with a proportional error model and interindividual variability (IIV) for clearance (CL) and central volume of distribution (V(1)) (CL, 0.462 liter/h ± 25%; V(1), 8.33 liters ± 29%; intercompartmental clearance [Q], 1.25 liters/h; peripheral volume of distribution [V(2)], 3.59 liters). Concentration data for LAMB best fitted a two-compartment model with a proportional error model and IIV for all parameters (CL, 1.22 liters/h ± 64%; V(1), 19.2 liters ± 38%; Q, 2.18 liters/h ± 47%; V(2), 52.8 liters ± 84%). Internal model validation showed predictability and robustness of both models. None of the covariates tested (LAMB or CAS comedication, gender, body weight, age, body surface area, serum bilirubin, and creatinine clearance) further improved the models. In summary, the disposition of LAMB and CAS was best described by two-compartment models. Drug exposures in aHSCT patients were comparable to those in other populations, and no PK interactions were observed between the two compounds.

Indexed as

Hematopoietic Stem Cell TransplantationAdolescentAdultAgranulocytosisAmphotericin BAntifungal AgentsCaspofunginDrug Administration ScheduleEchinocandinsFemaleFeverHumansLipopeptidesMaleMiddle AgedModels, StatisticalAmphotericin BAntifungal AgentsCaspofunginEchinocandinsLipopeptidesliposomal amphotericin B

Identifiers

PMID22083471
PMCPMC3256056

What OpenQuestion holds

Textmetadata
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.