{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2025,10,9]],"date-time":"2025-10-09T12:42:03Z","timestamp":1760013723998},"reference-count":28,"publisher":"BMJ","issue":"7","content-domain":{"domain":["bmj.com"],"crossmark-restriction":true},"short-container-title":["BMJ Open"],"accepted":{"date-parts":[[2016,6,14]]},"published-print":{"date-parts":[[2016,7]]},"abstract":"<jats:sec><jats:title>Objectives<\/jats:title><jats:p>To explore whether pharmacokinetic (PK) studies in paediatric patients are becoming less invasive. This will be evaluated by analysing the number of samples and volume of blood collected for each study within four different decades.<\/jats:p><\/jats:sec><jats:sec><jats:title>Methods<\/jats:title><jats:p>A systematic literature review was performed to identify PK papers describing number of samples and volume of blood collected in studies of children aged 0\u201318\u2005years. The following databases were searched: MEDLINE (1946 to December 2015), EMBASE (1974 to December 2015), International Pharmaceutical Abstracts (1970 to December 2015), CINAHL and Cochrane Library.<\/jats:p><\/jats:sec><jats:sec><jats:title>Results<\/jats:title><jats:p>A total of 549 studies were identified between 1974 and 2015. There were 52 studies between 1976 and 1985, 105 between 1986 and 1995, 201 between 1996 and 2005 and 191 between 2006 and 2015. The number of blood samples collected per participant increased between the first two decades (p=0.013), but there was a decrease in the number of samples in the subsequent two decades (p=0.044 and p&lt;0.001, respectively). Comparing the first and last decades, there has been no change in the number of blood samples collected. There were no significant differences in volume collected per sample or total volume per child in any of the age groups. There was however a significant difference in the frequency of blood sampling between population PK studies (median 5 (IQR 3\u20137)) and non-population PK studies (median 8 (IQR 6\u201310); p=&lt;0.001).<\/jats:p><\/jats:sec><jats:sec><jats:title>Conclusions<\/jats:title><jats:p>The number of blood samples collected for PK studies in children rose in 1985\u20131995 and subsequently declined. There was no overall change in the volume of blood collected over the 4 decades. The usage of population PK methods reduces the frequency of blood sampling in children.<\/jats:p><\/jats:sec>","DOI":"10.1136\/bmjopen-2015-010484","type":"journal-article","created":{"date-parts":[[2016,7,19]],"date-time":"2016-07-19T01:30:00Z","timestamp":1468891800000},"page":"e010484","update-policy":"http:\/\/dx.doi.org\/10.1136\/crossmarkpolicy","source":"Crossref","is-referenced-by-count":8,"title":["Invasiveness of pharmacokinetic studies in children: a systematic review"],"prefix":"10.1136","volume":"6","author":[{"given":"Mohammed I","family":"Altamimi","sequence":"first","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Imti","family":"Choonara","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Helen","family":"Sammons","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]}],"member":"239","published-online":{"date-parts":[[2016,7,18]]},"reference":[{"key":"2024051515282554000_6.7.e010484.1","doi-asserted-by":"publisher","DOI":"10.1185\/1463009001527660"},{"key":"2024051515282554000_6.7.e010484.2","doi-asserted-by":"publisher","DOI":"10.1136\/jme.11.3.127"},{"key":"2024051515282554000_6.7.e010484.3","doi-asserted-by":"publisher","DOI":"10.1016\/S0304-3959(97)00062-6"},{"key":"2024051515282554000_6.7.e010484.4","first-page":"1","article-title":"The effects of lead exposure on urban children: the Institute of Child Health\/Southampton study","volume":"47","author":"Smith","year":"1983","journal-title":"Dev Med Child Neurol"},{"key":"2024051515282554000_6.7.e010484.5","first-page":"182","article-title":"Anterior interosseous nerve syndrome: unusual etiologies","volume":"64","author":"Saeed","year":"1983","journal-title":"Arch Phys Med Rehabil"},{"key":"2024051515282554000_6.7.e010484.6","unstructured":"World Health Organisation. WHO guidelines on drawing blood: best practices in phlebotomy. 2010."},{"key":"2024051515282554000_6.7.e010484.7","doi-asserted-by":"crossref","first-page":"3277","DOI":"10.1016\/j.jchromb.2010.10.009","article-title":"Dexamethasone quantification in dried blood spot samples using LC\u2013MS: the potential for application to neonatal pharmacokinetic studies","volume":"878","author":"Patel","year":"2010","journal-title":"J Chromatogr B Analyt Technol Biomed Life Sci"},{"key":"2024051515282554000_6.7.e010484.8","doi-asserted-by":"publisher","DOI":"10.1136\/adc.2009.177592"},{"key":"2024051515282554000_6.7.e010484.9","doi-asserted-by":"crossref","first-page":"114","DOI":"10.1208\/ps020332","article-title":"Nonlinearity detection: advantages of nonlinear mixed-effects modeling","volume":"2","author":"Jonsson","year":"2000","journal-title":"AAPS PharmSci Tech"},{"key":"2024051515282554000_6.7.e010484.10","unstructured":"Agency EM . Guideline on the Investigation of medicinal products in the term and preterm neonate. http:\/\/www.ema.europa.eu\/docs\/en_GB\/document_library\/Scientific_guideline\/2009\/09\/WC500003750.pdf (accessed 5 Apr 2016)."},{"key":"2024051515282554000_6.7.e010484.11","unstructured":"Categories of research that may be reviewed by the institutional review board (IRB) through an expedited review procedure. US Health and Human Services Office for Human Research Protections. http:\/\/www.fda.gov\/ScienceResearch\/SpecialTopics\/RunningClinicalTrials\/ucm119074.htm (accessed 5 Apr 2016)."},{"key":"2024051515282554000_6.7.e010484.12","doi-asserted-by":"publisher","DOI":"10.2196\/jmir.8.4.e25"},{"key":"2024051515282554000_6.7.e010484.13","doi-asserted-by":"crossref","unstructured":"Rose K , St\u00f6tter H . ICH E 11: Clinical investigation of medicinal products in the paediatric population. Guide to paediatric clinical research. Basel: Karger, 2007:33\u20137.","DOI":"10.1159\/000097774"},{"key":"2024051515282554000_6.7.e010484.14","doi-asserted-by":"publisher","DOI":"10.1097\/00000542-199511000-00006"},{"key":"2024051515282554000_6.7.e010484.15","doi-asserted-by":"publisher","DOI":"10.1177\/0091270007299759"},{"key":"2024051515282554000_6.7.e010484.16","doi-asserted-by":"publisher","DOI":"10.1016\/j.ejca.2006.03.023"},{"key":"2024051515282554000_6.7.e010484.17","doi-asserted-by":"crossref","first-page":"9","DOI":"10.1186\/1471-227X-12-9","article-title":"Is the APLS formula used to calculate weight-for-age applicable to a Trinidadian population?","volume":"12","author":"Ali","year":"2012","journal-title":"BMC Emerg Med"},{"key":"2024051515282554000_6.7.e010484.18","doi-asserted-by":"publisher","DOI":"10.1007\/BF01061030"},{"key":"2024051515282554000_6.7.e010484.19","doi-asserted-by":"publisher","DOI":"10.1016\/S0022-3476(87)80219-6"},{"issue":"3","key":"2024051515282554000_6.7.e010484.20","doi-asserted-by":"crossref","first-page":"627","DOI":"10.1542\/peds.104.S3.627","article-title":"Optimal sampling theory: an overview of its application to pharmacokinetic studies in infants and children","volume":"104","author":"Reed","year":"1999","journal-title":"Pediatrics"},{"key":"2024051515282554000_6.7.e010484.21","doi-asserted-by":"publisher","DOI":"10.2471\/BLT.10.080010"},{"key":"2024051515282554000_6.7.e010484.22","doi-asserted-by":"crossref","first-page":"866","DOI":"10.1128\/AAC.23.6.866","article-title":"Pharmacokinetics of cefoperazone in full-term and premature neonates","volume":"23","author":"Rosenfeld","year":"1983","journal-title":"Antimicrob Agents Chemother"},{"key":"2024051515282554000_6.7.e010484.23","doi-asserted-by":"publisher","DOI":"10.2165\/11319970-000000000-00000"},{"key":"2024051515282554000_6.7.e010484.24","first-page":"290","article-title":"Blood sample collection from a peripheral catheter system compared with phlebotomy","volume":"23","author":"Seemann","year":"2000","journal-title":"J Intraven Nurs"},{"key":"2024051515282554000_6.7.e010484.25","doi-asserted-by":"publisher","DOI":"10.1016\/S0196-0644(05)81705-6"},{"key":"2024051515282554000_6.7.e010484.26","doi-asserted-by":"publisher","DOI":"10.1136\/adc.2004.069328"},{"key":"2024051515282554000_6.7.e010484.27","doi-asserted-by":"crossref","first-page":"348","DOI":"10.1002\/j.1875-9114.1991.tb04301.x","article-title":"Elevated phenytoin concentration caused by sampling through the drug-administration catheter","volume":"11","author":"Murphy","year":"1991","journal-title":"Pharmacotherapy"},{"key":"2024051515282554000_6.7.e010484.28","doi-asserted-by":"publisher","DOI":"10.1007\/BF00496419"}],"container-title":["BMJ Open"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/syndication.highwire.org\/content\/doi\/10.1136\/bmjopen-2015-010484","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2024,5,15]],"date-time":"2024-05-15T22:28:41Z","timestamp":1715812121000},"score":1,"resource":{"primary":{"URL":"https:\/\/bmjopen.bmj.com\/lookup\/doi\/10.1136\/bmjopen-2015-010484"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2016,7]]},"references-count":28,"journal-issue":{"issue":"7","published-online":{"date-parts":[[2016,7,18]]},"published-print":{"date-parts":[[2016,7]]}},"alternative-id":["10.1136\/bmjopen-2015-010484"],"URL":"https:\/\/doi.org\/10.1136\/bmjopen-2015-010484","relation":{},"ISSN":["2044-6055","2044-6055"],"issn-type":[{"value":"2044-6055","type":"print"},{"value":"2044-6055","type":"electronic"}],"subject":[],"published":{"date-parts":[[2016,7]]}}}