Evidence map›Paper›PMID 28429492›Full record

ArticleBritish journal of clinical pharmacology2017

Body weight, gender and pregnancy affect enantiomer-specific ketorolac pharmacokinetics.

Pyry A Välitalo, Heidi Kemppainen, Aida Kulo, Anne Smits, Kristel van Calsteren, Klaus T Olkkola, Jan de Hoon, Catherijne A J Knibbe, Karel Allegaert

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Article in British journal of clinical pharmacology, 2017. 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
1.7field-weighted citation impact, top 17% 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, 12 citations in OpenAlex.

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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

9 authors at 7 institutions in 4 countries.

Pyry A VälitaloDivision of Pharmacology, Leiden Academic Centre for Drug Research, Leiden University, Leiden, the Netherlands.
Heidi KemppainenDivision of Pharmacology, Leiden Academic Centre for Drug Research, Leiden University, Leiden, the Netherlands.
Aida KuloInstitute of Pharmacology, Clinical Pharmacology and Toxicology, Faculty of Medicine, University of Sarajevo, Sarajevo, Bosnia and Herzegovina.
Anne SmitsNeonatal Intensive Care Unit, University Hospitals Leuven, Leuven, Belgium.
Kristel van CalsterenDepartment of Obstetrics and Gynecology, University Hospitals Leuven, Leuven, Belgium.
Klaus T OlkkolaDepartment of Anaesthesiology, Intensive Care and Pain Medicine, University of Helsinki and Helsinki University Hospital, Helsinki, Finland.
Jan de HoonDepartment of Pharmaceutical and Pharmacological Sciences, KU Leuven, Belgium.
Catherijne A J KnibbeDivision of Pharmacology, Leiden Academic Centre for Drug Research, Leiden University, Leiden, the Netherlands.
Karel AllegaertDepartment of Development and Regeneration, University Hospitals Leuven, Leuven, Belgium.
KU Leuven · BECentre for Human Drug Research · NLErasmus MC - Sophia Children’s Hospital · NLLeiden University · NLUniversity of Eastern Finland · FIUniversity of Helsinki · FIUniversity of Sarajevo · BA

Funding

No grant is acknowledged in the PubMed record.

6 · The paper itself

Abstract

aimsAlthough ketorolac analgesia is linked only to the S-enantiomer, there is limited information on the stereo-selective pharmacokinetics of this agent. We studied the stereo-selective pharmacokinetics of ketorolac in a pooled dataset of two studies, with women at delivery and 4-5 months postpartum, and males and nonpregnant females.

methodsNonlinear mixed-effect modelling was used to evaluate the stereo-selective pharmacokinetics of ketorolac tromethamine after a single intravenous injection immediately after delivery (n = 41), 4-5 months postpartum (n = 8, paired), and in male (n = 12) and nonpregnant female (n = 14) subjects. All of the males and six of the nonpregnant females were recruited from another study, in which they were undergoing blood sampling for 24 h. All remaining cases underwent blood sampling for 8 h.

resultsFor both the R- and S-enantiomers, body weight affected ketorolac clearance. In addition, clearance for both enantiomers was 36% [95% confidence interval (CI) 15%, 58%] higher in male than in female subjects of the same body weight, and 55% (95% CI 33%, 78%) higher in women at delivery than in nonpregnant women of the same body weight. Women at delivery also had a 27% (95% CI 8%, 46%) higher distribution volume than nonpregnant women. The proportional effects of the covariates were not significantly different for the two ketorolac enantiomers.

conclusionsBesides the anticipated impact of body weight on clearance, R- and S-ketorolac clearance is increased in male subjects and in women at delivery. To reach an exposure equivalent to that in nonpregnant women, males should receive a 36% increased ketorolac dose and pregnant women a 55% increased dose, in addition to a dose adjustment by body weight.

Indexed as

Body WeightSex FactorsAdultAnti-Inflammatory Agents, Non-SteroidalFemaleHumansKetorolac TromethamineMaleMeta-Analysis as TopicNonlinear DynamicsPostpartum PeriodPregnancyStereoisomerismYoung AdultAnti-Inflammatory Agents, Non-SteroidalKetorolac Tromethamineketorolacnonlinear mixed-effects modellingpainpopulation pharmacokineticspregnancy

Identifiers

PMID28429492
PMCPMC5555864
OpenAlexW2607439821

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.