{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,8,3]],"date-time":"2026-08-03T14:18:05Z","timestamp":1785766685751,"version":"3.56.0"},"reference-count":25,"publisher":"Wiley","issue":"8","license":[{"start":{"date-parts":[[2019,6,20]],"date-time":"2019-06-20T00:00:00Z","timestamp":1560988800000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/onlinelibrary.wiley.com\/termsAndConditions#vor"}],"funder":[{"DOI":"10.13039\/100004325","name":"AstraZeneca","doi-asserted-by":"publisher","id":[{"id":"10.13039\/100004325","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["Brit J Clinical Pharma"],"published-print":{"date-parts":[[2019,8]]},"abstract":"<jats:sec><jats:title>Aims<\/jats:title><jats:p>To quantitatively compare pharmacokinetics (PK) and the exposure\u2013response (ER) relationship of the sodium\u2010glucose cotransporter\u20102 inhibitor, dapagliflozin, between adolescents\/young adults and adults with type 1 diabetes mellitus (T1DM).<\/jats:p><\/jats:sec><jats:sec><jats:title>Methods<\/jats:title><jats:p>Data from 2 clinical studies for dapagliflozin were analysed using a non\u2010linear mixed\u2010effects approach. The PK and the relationship between dapagliflozin exposure and response (24\u2010hour urinary glucose excretion) were characterized. PK was evaluated using a 2\u2010compartment model with first\u2010order absorption while the exposure response\u2010relationship was analysed using a sigmoidal maximal\u2010effect model. The 24\u2010hour median blood glucose, estimated glomerular filtration rate (eGFR), sex, age and body weight were evaluated as covariates.<\/jats:p><\/jats:sec><jats:sec><jats:title>Results<\/jats:title><jats:p>A 2\u2010compartment model with first order absorption provided a reasonable fit to the dapagliflozin PK data. Body weight was found to be a significant covariate on dapagliflozin exposure. The ER relationship was best described by a sigmoidal maximal effect model with 24\u2010hour median blood glucose and eGFR as significant covariates on maximal effect. In accordance with the observed data, model\u2010predicted urinary glucose excretion response following 10\u00a0mg dapagliflozin dose was higher in the study in adolescents\/young adults (138.0\u00a0g\/24\u00a0h) compared to adults (70.5\u00a0g\/24\u00a0h) with T1DM. This is linked to higher eGFR and 24\u2010hour median blood glucose in this trial.<\/jats:p><\/jats:sec><jats:sec><jats:title>Conclusions<\/jats:title><jats:p>Dapagliflozin PK and ER relationship were similar in the 2 analysed studies after accounting for covariate effects. These results suggest that no dose adjustment is required for adolescent patients with T1DM.<\/jats:p><\/jats:sec>","DOI":"10.1111\/bcp.13981","type":"journal-article","created":{"date-parts":[[2019,5,11]],"date-time":"2019-05-11T14:11:25Z","timestamp":1557583885000},"page":"1820-1828","source":"Crossref","is-referenced-by-count":14,"title":["Comparison of pharmacokinetics and the exposure\u2013response relationship of dapagliflozin between adolescent\/young adult and adult patients with type 1 diabetes mellitus"],"prefix":"10.1111","volume":"85","author":[{"given":"David","family":"Busse","sequence":"first","affiliation":[{"name":"Quantitative Clinical Pharmacology, Early Clinical Development, IMED Biotech Unit AstraZeneca  Gothenburg Sweden"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Weifeng","family":"Tang","sequence":"additional","affiliation":[{"name":"Quantitative Clinical Pharmacology, Early Clinical Development, IMED Biotech Unit AstraZeneca  Gaithersburg MD USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Markus","family":"Scheerer","sequence":"additional","affiliation":[{"name":"Diabetes Medical Department AstraZeneca GmbH  Wedel Germany"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Thomas","family":"Danne","sequence":"additional","affiliation":[{"name":"AUF DER BULT Children's and Youth Hospital  Hannover Germany"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-8051-5562","authenticated-orcid":false,"given":"Torben","family":"Biester","sequence":"additional","affiliation":[{"name":"AUF DER BULT Children's and Youth Hospital  Hannover Germany"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Viktor","family":"Sokolov","sequence":"additional","affiliation":[{"name":"M&amp;S Decisions  Moscow Russia"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"David","family":"Boulton","sequence":"additional","affiliation":[{"name":"Quantitative Clinical Pharmacology, Early Clinical Development, IMED Biotech Unit AstraZeneca  Gaithersburg MD USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-4492-5243","authenticated-orcid":false,"given":"Joanna","family":"Parkinson","sequence":"additional","affiliation":[{"name":"Quantitative Clinical Pharmacology, Early Clinical Development, IMED Biotech Unit AstraZeneca  Gothenburg Sweden"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"311","published-online":{"date-parts":[[2019,6,20]]},"reference":[{"key":"e_1_2_9_2_1","doi-asserted-by":"publisher","DOI":"10.1056\/NEJMoa1610187"},{"key":"e_1_2_9_3_1","doi-asserted-by":"publisher","DOI":"10.3892\/etm.2016.3039"},{"key":"e_1_2_9_4_1","doi-asserted-by":"crossref","first-page":"1378","DOI":"10.2337\/dc15-2399","article-title":"Mortality in type 1 diabetes in the DCCT\/EDIC vs the general population","volume":"39","author":"DCCT\/EDIC","year":"2016","journal-title":"Diabetes Care"},{"key":"e_1_2_9_5_1","doi-asserted-by":"publisher","DOI":"10.2337\/dc15-0078"},{"key":"e_1_2_9_6_1","volume-title":"Farxiga [Prescribing Information]"},{"key":"e_1_2_9_7_1","doi-asserted-by":"publisher","DOI":"10.1021\/jm701272q"},{"key":"e_1_2_9_8_1","doi-asserted-by":"publisher","DOI":"10.2337\/db07-1472"},{"key":"e_1_2_9_9_1","doi-asserted-by":"publisher","DOI":"10.1007\/s40262-013-0104-3"},{"key":"e_1_2_9_10_1","doi-asserted-by":"publisher","DOI":"10.1016\/S2213-8587(17)30308-X"},{"key":"e_1_2_9_11_1","doi-asserted-by":"publisher","DOI":"10.2337\/dc18-0623"},{"key":"e_1_2_9_12_1","doi-asserted-by":"publisher","DOI":"10.1111\/dom.12425"},{"key":"e_1_2_9_13_1","doi-asserted-by":"publisher","DOI":"10.1111\/dom.12975"},{"key":"e_1_2_9_14_1","doi-asserted-by":"publisher","DOI":"10.2337\/dc13-2955"},{"key":"e_1_2_9_15_1","doi-asserted-by":"publisher","DOI":"10.1111\/bph.13882"},{"key":"e_1_2_9_16_1","doi-asserted-by":"publisher","DOI":"10.2215\/CJN.01640309"},{"key":"e_1_2_9_17_1","doi-asserted-by":"publisher","DOI":"10.7326\/0003-4819-145-4-200608150-00004"},{"key":"e_1_2_9_18_1","unstructured":"MelinJ ParkinsonJ Reki\u0107D Hamr\u00e9nB PenlandRC BoultonDW TangW.Dapagliflozin pharmacokinetics is similar in adults with type 1 and type 2 diabetes mellitus. In: Annual Meeting of the Population Approach Group in Europe 2018: 27. Abstr 8427."},{"key":"e_1_2_9_19_1","first-page":"236","article-title":"Comparison of the pharmacokinetics and pharmacodynamics of dapagliflozin in patients with type 1 vs type 2 diabetes mellitus","volume":"18","author":"Tang W","year":"2016","journal-title":"J Med Chem"},{"key":"e_1_2_9_20_1","doi-asserted-by":"publisher","DOI":"10.1111\/dom.12647"},{"key":"e_1_2_9_21_1","doi-asserted-by":"publisher","DOI":"10.1111\/dom.13586"},{"key":"e_1_2_9_22_1","doi-asserted-by":"publisher","DOI":"10.1016\/S0169-2607(98)00067-4"},{"key":"e_1_2_9_23_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.cmpb.2003.11.003"},{"key":"e_1_2_9_24_1","doi-asserted-by":"publisher","DOI":"10.1007\/s10928-007-9066-0"},{"key":"e_1_2_9_25_1","doi-asserted-by":"publisher","DOI":"10.1093\/nar\/gkx1121"},{"key":"e_1_2_9_26_1","doi-asserted-by":"publisher","DOI":"10.1111\/bph.13883"}],"container-title":["British Journal of Clinical Pharmacology"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/api.wiley.com\/onlinelibrary\/tdm\/v1\/articles\/10.1111%2Fbcp.13981","content-type":"application\/pdf","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/onlinelibrary.wiley.com\/doi\/pdf\/10.1111\/bcp.13981","content-type":"application\/pdf","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/onlinelibrary.wiley.com\/doi\/full-xml\/10.1111\/bcp.13981","content-type":"application\/xml","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/bpspubs.onlinelibrary.wiley.com\/doi\/pdf\/10.1111\/bcp.13981","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2023,9,9]],"date-time":"2023-09-09T21:48:22Z","timestamp":1694296102000},"score":1,"resource":{"primary":{"URL":"https:\/\/bpspubs.onlinelibrary.wiley.com\/doi\/10.1111\/bcp.13981"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2019,6,20]]},"references-count":25,"journal-issue":{"issue":"8","published-print":{"date-parts":[[2019,8]]}},"alternative-id":["10.1111\/bcp.13981"],"URL":"https:\/\/doi.org\/10.1111\/bcp.13981","archive":["Portico"],"relation":{},"ISSN":["0306-5251","1365-2125"],"issn-type":[{"value":"0306-5251","type":"print"},{"value":"1365-2125","type":"electronic"}],"subject":[],"published":{"date-parts":[[2019,6,20]]}}}