Evidence map›Paper›PMID 36702944›Full record

ArticleScientific reports2023

Effect of pharmacogenetic variations on praziquantel plasma concentration and safety outcomes among school children in Rwanda.

Abbie Barry, Joseph Kabatende, Nigus Fikrie Telele, Rajabu Hussein Mnkugwe, Michael Mugisha, Lazare Ntirenganya, Emile Bienvenu, Eleni Aklillu

Open access · goldAbstract read
In one paragraph

Article in Scientific reports, 2023. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 4 papers.

0numbers the graph read from it
0cells of the map it votes in
4citing papers in PubMed
2.5field-weighted citation impact, top 13% 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

4 citing papers in PubMed, 9 citations in OpenAlex.

  1. Article
  2. Article
  3. Article
  4. Efficacy of Single-Dose Praziquantel for the Treatment ofPathogens (Basel, Switzerland) · 2023
    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

8 authors at 5 institutions in 3 countries.

Abbie BarryDivision of Clinical Pharmacology, Department of Laboratory Medicine, Karolinska Institutet at Karolinska University Hospital, Huddinge, Stockholm, Sweden.
Joseph KabatendeDivision of Clinical Pharmacology, Department of Laboratory Medicine, Karolinska Institutet at Karolinska University Hospital, Huddinge, Stockholm, Sweden.
Nigus Fikrie TeleleDivision of Clinical Pharmacology, Department of Laboratory Medicine, Karolinska Institutet at Karolinska University Hospital, Huddinge, Stockholm, Sweden.
Rajabu Hussein MnkugweDepartment of Clinical Pharmacology, School of Medicine, Muhimbili University of Health and Allied Sciences, Dar es Salaam, Tanzania.
Michael MugishaCollege of Medicine and Health Sciences, University of Rwanda, KK 737, Kigali, Rwanda.
Lazare NtirenganyaRwanda Food and Drugs Authority, Nyarutarama Plaza, KG 9 Avenue, Kigali, Rwanda.
Emile BienvenuRwanda Food and Drugs Authority, Nyarutarama Plaza, KG 9 Avenue, Kigali, Rwanda.
Eleni AklilluDivision of Clinical Pharmacology, Department of Laboratory Medicine, Karolinska Institutet at Karolinska University Hospital, Huddinge, Stockholm, Sweden. eleni.aklillu@ki.se.
Karolinska University Hospital · SERwanda Development Board · RWKarolinska Institutet · SEMuhimbili University of Health and Allied Sciences · TZUniversity of Rwanda · RW

Funding

No grant is acknowledged in the PubMed record.

6 · The paper itself

Abstract

School-based mass drug administration (MDA) of Praziquantel (PZQ) is the global intervention strategy for elimination of schistosomiasis. Genetic variations in drug metabolizing enzymes and transporter proteins influences drug exposure and treatment outcomes, but data on PZQ pharmacokinetics and safety outcomes are scarce. We investigated the effect of pharmacogenetics variations on PZQ plasma concentrations and safety outcomes among 462 Rwandan schoolchildren who received single dose PZQ and albendazole in MDA. Genotyping for common functional variant alleles CYP3A4*1B, CYP3A5 (*3, *6, *7), CYP2C19 (*2, *3, *17), CYP2C9 (*2, *3) and CYP2J2*7 were done. Plasma concentration of PZQ, cis-4-OH-PZQ and trans-4-OH-PZQ were measured using LC/MS/MS. Active safety monitoring was done on days 1, 2, and 7 post-MDA. CYP2C9 and CYP2C19 genotypes were significantly associated with PZQ plasma concentrations and its cis- and trans-4-OH-PZQ/PZQ metabolic ratios (MR). CYP2C9*2 and CYP2C9*3 carriers had significantly higher PZQ concentration (p = 0.02), lower trans-4-OH-PZQ/PZQ (p < 0.001), and cis-4-OH-PZQ/PZQ (p = 0.02) MR. CYP2C19 (*2, *3) carriers had significantly higher plasma PZQ concentration than CYP2C19 *1/*1 and CYP2C19 *17 carriers (*1/*17 or *17/*17) (p < 0.001). CYP3A4 was significantly associated with cis-4-OH-PZQ MR (p = 0.04). Lower cis-4-OH-PZQ/PZQ MR (p < 0.0001) was a predictor of MDA-associated adverse events, but no significant association with genotypes were found. In conclusion, CYP2C9 and CYP2C19 genotypes significantly influence the plasma PZQ concentration and its MR. Lower cis-4-OH-PZQ/PZQ MR is significant predictor of adverse events following MDA.

Indexed as

Cytochrome P-450 CYP3APraziquantelChildCytochrome P-450 CYP2C19Cytochrome P-450 CYP2C9HumansPharmacogeneticsRwandaTandem Mass SpectrometryCytochrome P-450 CYP2C19Cytochrome P-450 CYP2C9Cytochrome P-450 CYP3APraziquantel

Identifiers

PMID36702944
PMCPMC9879930
OpenAlexW4318067780

What Socratic holds

Textmetadata
LicenceCC BY
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.