Evidence map›Paper›PMID 23090703›Full record

Trial reportEuropean journal of clinical pharmacology2013

CYP2C19 genotype has a major influence on labetalol pharmacokinetics in healthy male Chinese subjects.

Sze Wa Chan, Miao Hu, Sara Shun Wah Ko, Catherine Wing Yan Tam, Benny Siu Pong Fok, Ophelia Qi Ping Yin, Moses Sing Sum Chow, Brian Tomlinson

Abstract readClinical Trial
PubMed Publisher
In one paragraph

Trial report in European journal of clinical pharmacology, 2013. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 6 papers.

0numbers the graph read from it
0cells of the map it votes in
6citing papers in PubMed
0.4field-weighted citation impact, top 29% 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

6 citing papers in PubMed, 12 citations in OpenAlex.

  1. Article
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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 4 institutions in 5 countries.

Sze Wa ChanDepartment of Medicine and Therapeutics, The Chinese University of Hong Kong-Prince of Wales Hospital, Shatin, New Territories, Hong Kong.
Miao Hu
Sara Shun Wah Ko
Catherine Wing Yan Tam
Benny Siu Pong Fok
Ophelia Qi Ping Yin
Moses Sing Sum Chow
Brian Tomlinson
Chinese University of Hong Kong · CNImperial College London · GBRoyal College of Surgeons in Ireland · IEWestern University of Health Sciences · US

Funding

No grant is acknowledged in the PubMed record.

6 · The paper itself

Abstract

purposeThe pharmacokinetics (PK) of labetalol show wide inter-subject variability, but the genetic causes for this are largely undetermined. This study was performed to examine whether common polymorphisms in UGT1A1, UGT2B7, CYP2C19 and ABCB1 affect the PK of labetalol.

methodsThe PK of labetalol were determined in 37 Chinese healthy male subjects who took a single oral dose of 200 mg labetalol. Plasma concentrations of labetalol were determined by a high-performance liquid chromatographic method. Subjects were genotyped for the CYP2C19 2 and 3, UGT1A1 6, 28 and 60, UGT2B7 2 and ABCB1 1236C>T, 2677G>T/A and 3435C>T polymorphisms.

resultsSubjects with the CYP2C19 2/ 2 genotype had a higher peak concentration (255.5 ± 80.1 vs. 156.0  ±  66.3 ng/mL; P < 0.05) and area under the concentration-time curve (AUC0-∞; 1,473.7 ± 493.6 vs. 502.8 ± 176.1 ng[Symbol: see text]h/mL; P < 0.001) than subjects with 60 or 28, and UGT2B7 2 did not result in a significant effect. Subjects with ABCB1 2677TA or TT or ABCB1 3435TT genotypes had higher AUC0-∞ and lower total clearance than the wild-types (P < 0.05), but this appeared to be related to the distribution of CYP2C19 genotypes. The CYP2C19 genotype appeared to be the only predictor of labetalol concentrations, accounting for approximately 60 % of the total variance in the AUC0-∞.

conclusionOur results suggest that the PK of labetalol are significantly affected by the common CYP2C19 polymorphisms in individuals of Chinese ethnicity. Future larger studies are needed to evaluate the effect of CYP2C19 and UGT1A1 polymorphisms on the PK of labetalol stereoisomers and the pharmacodynamic effects.

Indexed as

Polymorphism, GeneticAdministration, OralAdolescentAdrenergic beta-AntagonistsAdultAryl Hydrocarbon HydroxylasesAsian PeopleChinaChromatography, High Pressure LiquidCross-Over StudiesCytochrome P-450 CYP2C19Dose-Response Relationship, DrugGenotypeHumansLabetalolMaleAdrenergic beta-AntagonistsAryl Hydrocarbon HydroxylasesCYP2C19 protein, humanCytochrome P-450 CYP2C19Labetalol

Identifiers

PMID23090703
OpenAlexW2024865654

What OpenQuestion holds

Textmetadata
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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.