{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,1,21]],"date-time":"2026-01-21T12:15:08Z","timestamp":1768997708245,"version":"3.49.0"},"reference-count":21,"publisher":"Wiley","issue":"4","license":[{"start":{"date-parts":[[2024,12,4]],"date-time":"2024-12-04T00:00:00Z","timestamp":1733270400000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/creativecommons.org\/licenses\/by-nc-nd\/4.0\/"}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["Brit J Clinical Pharma"],"published-print":{"date-parts":[[2025,4]]},"abstract":"<jats:sec><jats:title>Aims<\/jats:title><jats:p>A 42\u2010year\u2010old male developed chronic primary hypoparathyroidism after total thyroidectomy. Conventional therapy led to recurrent nephrolithiasis and therefore rhPTH(1\u201084) (parathyroid hormone [PTH]) treatment was considered. According to the dosing guideline for PTH, calcium plasma levels are adequately controlled with once\u2010daily administration. However, the effect on urinary calcium excretion is only transient and hence does not lower the risk of nephrolithiasis. This raises the question of whether multiple\u2010daily or continuous administration of PTH is more effective in lowering urinary calcium excretion. We aimed to construct a pharmacokinetic\u2010pharmacodynamic (PKPD) model to answer this question.<\/jats:p><\/jats:sec><jats:sec><jats:title>Methods<\/jats:title><jats:p>A single patient was treated with intermittent PTH followed by off\u2010label continuous infusion of PTH. PTH was measured in plasma, calcium and phosphate in plasma and urine. A one\u2010compartment PKPD model for PTH was developed with Edsim++. The effect of PTH was described by the relative clearance of calcium and phosphate.<\/jats:p><\/jats:sec><jats:sec><jats:title>Results<\/jats:title><jats:p>The PKPD model for PTH showed visually a marked effect on phosphate clearance, but less on calcium clearance. During the study, the patient also received medication that influenced calcium homeostasis but to a lesser extent phosphate homeostasis. Therefore, phosphate was chosen as the effect parameter, resulting in an EC50 of 6.3\u00a0pmol\/L PTH.<\/jats:p><\/jats:sec><jats:sec><jats:title>Conclusions<\/jats:title><jats:p>The PKPD model for PTH was completed with the unique data of a single patient who received PTH according to various dosing regimens, including continuous infusion. Continuous administration of PTH is favoured because it permanently increases the phosphate clearance and therefore needs to be further investigated.<\/jats:p><\/jats:sec>","DOI":"10.1111\/bcp.16342","type":"journal-article","created":{"date-parts":[[2024,12,5]],"date-time":"2024-12-05T06:00:32Z","timestamp":1733378432000},"page":"1233-1240","source":"Crossref","is-referenced-by-count":1,"title":["Personalized parathyroid hormone therapy for hypoparathyroidism: Insights from pharmacokinetic\u2010pharmacodynamic modelling"],"prefix":"10.1111","volume":"91","author":[{"ORCID":"https:\/\/orcid.org\/0000-0002-6766-1570","authenticated-orcid":false,"given":"Maira","family":"Visscher","sequence":"first","affiliation":[{"name":"Department of Clinical Pharmacy and Pharmacology, University of Groningen University Medical Center Groningen  Groningen the Netherlands"},{"name":"Department of Pharmaceutical Technology and Biopharmacy University of Groningen  Groningen the Netherlands"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Manon","family":"Schuls\u2010Fouchier","sequence":"additional","affiliation":[{"name":"Department of Clinical Pharmacy and Pharmacology, University of Groningen University Medical Center Groningen  Groningen the Netherlands"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Annika M. A.","family":"Berends","sequence":"additional","affiliation":[{"name":"Department of Endocrinology, University of Groningen University Medical Center Groningen  Groningen the Netherlands"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Anneke C.","family":"Muller Kobold","sequence":"additional","affiliation":[{"name":"Department of Laboratory Medicine, University of Groningen University Medical Center Groningen  Groningen the Netherlands"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Nieko C.","family":"Punt","sequence":"additional","affiliation":[{"name":"Department of Clinical Pharmacy and Pharmacology, University of Groningen University Medical Center Groningen  Groningen the Netherlands"},{"name":"Medimatics  Maastricht the Netherlands"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Daan J.","family":"Touw","sequence":"additional","affiliation":[{"name":"Department of Clinical Pharmacy and Pharmacology, University of Groningen University Medical Center Groningen  Groningen the Netherlands"},{"name":"Department of Pharmaceutical Analysis University of Groningen  Groningen the Netherlands"}],"role":[{"role":"author","vocabulary":"crossref"}]}],"member":"311","published-online":{"date-parts":[[2024,12,4]]},"reference":[{"key":"e_1_2_10_2_1","volume-title":"Parathyroid imaging","author":"Kluijfhout WP","year":"2017"},{"key":"e_1_2_10_3_1","doi-asserted-by":"publisher","DOI":"10.1007\/s00424\u2010018\u20102231\u2010z"},{"key":"e_1_2_10_4_1","doi-asserted-by":"publisher","DOI":"10.1172\/JCI110106"},{"key":"e_1_2_10_5_1","doi-asserted-by":"publisher","DOI":"10.1002\/jbmr.483"},{"key":"e_1_2_10_6_1","doi-asserted-by":"publisher","DOI":"10.17691\/stm2020.12.2.13"},{"key":"e_1_2_10_7_1","doi-asserted-by":"publisher","DOI":"10.1210\/jc.2015\u20103907"},{"key":"e_1_2_10_8_1","volume-title":"Harrison's principles of internal medicine, 20e","author":"Potts JJT","year":"2018"},{"key":"e_1_2_10_9_1","doi-asserted-by":"publisher","DOI":"10.1002\/jbmr.4691"},{"key":"e_1_2_10_10_1","volume-title":"Natpar: EPAR \u2013 product information: European Medicines Agency"},{"key":"e_1_2_10_11_1","doi-asserted-by":"publisher","DOI":"10.1002\/jbmr.1964"},{"key":"e_1_2_10_12_1","doi-asserted-by":"publisher","DOI":"10.1002\/cpt.1200"},{"key":"e_1_2_10_13_1","doi-asserted-by":"publisher","DOI":"10.3390\/pharmaceutics14061161"},{"key":"e_1_2_10_14_1","doi-asserted-by":"publisher","DOI":"10.1128\/aac.00003\u201022"},{"key":"e_1_2_10_15_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.clinthera.2014.04.001"},{"key":"e_1_2_10_16_1","volume-title":"Prescribing information NATPARA: NPS pharma"},{"key":"e_1_2_10_17_1","doi-asserted-by":"publisher","DOI":"10.1111\/bph.16179"},{"key":"e_1_2_10_18_1","first-page":"165","volume-title":"Regulatie en stoornissen van calcium\u2010, fosfaat\u2010 en magnesiumhuishouding","author":"Woittiez AJJ","year":"2005"},{"key":"e_1_2_10_19_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.bone.2009.08.053"},{"key":"e_1_2_10_20_1","volume-title":"Parathormoon (PTH, intact) in bloed 2024","author":"University Medical Center Groningen"},{"key":"e_1_2_10_21_1","volume-title":"FDA approves new drug for hypoparathyroidism, a rare disorder 2024","author":"US Food and Drug Administration"},{"key":"e_1_2_10_22_1","doi-asserted-by":"publisher","DOI":"10.1002\/jbmr.3824"}],"container-title":["British Journal of Clinical Pharmacology"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/bpspubs.onlinelibrary.wiley.com\/doi\/pdf\/10.1111\/bcp.16342","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2025,4,12]],"date-time":"2025-04-12T09:43:01Z","timestamp":1744450981000},"score":1,"resource":{"primary":{"URL":"https:\/\/bpspubs.onlinelibrary.wiley.com\/doi\/10.1111\/bcp.16342"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2024,12,4]]},"references-count":21,"journal-issue":{"issue":"4","published-print":{"date-parts":[[2025,4]]}},"alternative-id":["10.1111\/bcp.16342"],"URL":"https:\/\/doi.org\/10.1111\/bcp.16342","archive":["Portico"],"relation":{},"ISSN":["0306-5251","1365-2125"],"issn-type":[{"value":"0306-5251","type":"print"},{"value":"1365-2125","type":"electronic"}],"subject":[],"published":{"date-parts":[[2024,12,4]]}}}