{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,9,2]],"date-time":"2026-09-02T19:03:08Z","timestamp":1788375788721,"version":"build-2803163510"},"reference-count":35,"publisher":"Wiley","issue":"9","license":[{"start":{"date-parts":[[2017,5,14]],"date-time":"2017-05-14T00:00:00Z","timestamp":1494720000000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/onlinelibrary.wiley.com\/termsAndConditions#vor"}],"funder":[{"DOI":"10.13039\/501100001943","name":"Partnership for Advanced Computing in Europe AISBL","doi-asserted-by":"publisher","award":["JoinEU\u2010SEE and Eraweb scholarships"],"award-info":[{"award-number":["JoinEU\u2010SEE and Eraweb scholarships"]}],"id":[{"id":"10.13039\/501100001943","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["Brit J Clinical Pharma"],"published-print":{"date-parts":[[2017,9]]},"abstract":"<jats:sec><jats:title>Aims<\/jats:title><jats:p>Although ketorolac analgesia is linked only to the S\u2010enantiomer, there is limited information on the stereo\u2010selective pharmacokinetics of this agent. We studied the stereo\u2010selective pharmacokinetics of ketorolac in a pooled dataset of two studies, with women at delivery and 4\u20135\u00a0months postpartum, and males and nonpregnant females.<\/jats:p><\/jats:sec><jats:sec><jats:title>Methods<\/jats:title><jats:p>Nonlinear mixed\u2010effect modelling was used to evaluate the stereo\u2010selective pharmacokinetics of ketorolac tromethamine after a single intravenous injection immediately after delivery (<jats:italic>n<\/jats:italic>= 41), 4\u20135\u00a0months postpartum (<jats:italic>n<\/jats:italic>= 8, paired), and in male (<jats:italic>n<\/jats:italic>= 12) and nonpregnant female (<jats:italic>n<\/jats:italic>= 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\u00a0h.<\/jats:p><\/jats:sec><jats:sec><jats:title>Results<\/jats:title><jats:p>For both the R\u2010 and S\u2010enantiomers, 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.<\/jats:p><\/jats:sec><jats:sec><jats:title>Conclusions<\/jats:title><jats:p>Besides the anticipated impact of body weight on clearance, R\u2010 and S\u2010ketorolac 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.<\/jats:p><\/jats:sec>","DOI":"10.1111\/bcp.13311","type":"journal-article","created":{"date-parts":[[2017,4,21]],"date-time":"2017-04-21T06:55:11Z","timestamp":1492757711000},"page":"1966-1975","source":"Crossref","is-referenced-by-count":11,"title":["Body weight, gender and pregnancy affect enantiomer\u2010specific ketorolac pharmacokinetics"],"prefix":"10.1111","volume":"83","author":[{"given":"Pyry A.","family":"V\u00e4litalo","sequence":"first","affiliation":[{"name":"Division of Pharmacology, Leiden Academic Centre for Drug Research Leiden University Leiden the Netherlands"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Heidi","family":"Kemppainen","sequence":"additional","affiliation":[{"name":"Division of Pharmacology, Leiden Academic Centre for Drug Research Leiden University Leiden the Netherlands"},{"name":"School of Pharmacy University of Eastern Finland Kuopio Finland"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Aida","family":"Kulo","sequence":"additional","affiliation":[{"name":"Institute of Pharmacology, Clinical Pharmacology and Toxicology, Faculty of Medicine University of Sarajevo Sarajevo Bosnia and Herzegovina"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Anne","family":"Smits","sequence":"additional","affiliation":[{"name":"Neonatal Intensive Care Unit University Hospitals Leuven Leuven Belgium"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Kristel","family":"van Calsteren","sequence":"additional","affiliation":[{"name":"Department of Obstetrics and Gynecology University Hospitals Leuven Leuven Belgium"},{"name":"Department of Development and Regeneration University Hospitals Leuven Leuven Belgium"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Klaus T.","family":"Olkkola","sequence":"additional","affiliation":[{"name":"Department of Anaesthesiology, Intensive Care and Pain Medicine University of Helsinki and Helsinki University Hospital Helsinki Finland"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jan","family":"de Hoon","sequence":"additional","affiliation":[{"name":"Department of Pharmaceutical and Pharmacological Sciences KU Leuven Belgium"},{"name":"Center for Clinical Pharmacology University Hospitals Leuven Leuven Belgium"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Catherijne A. 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