{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,3,25]],"date-time":"2026-03-25T21:48:32Z","timestamp":1774475312291,"version":"3.50.1"},"reference-count":45,"publisher":"Wiley","issue":"9","license":[{"start":{"date-parts":[[2013,10,10]],"date-time":"2013-10-10T00:00:00Z","timestamp":1381363200000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/onlinelibrary.wiley.com\/termsAndConditions#vor"}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["Biopharm &amp; Drug Disp"],"published-print":{"date-parts":[[2013,12]]},"abstract":"<jats:title>ABSTRACT<\/jats:title><jats:p>Hydrochlorothiazide (HCTZ) is a thiazide diuretic used for the treatment of hypertension and edema associated with fluid overload conditions such as congestive heart failure (CHF). A population\u2010based meta\u2010analysis approach in NONMEM\u00ae was used to develop a PK model to characterize the time\u2010course of HCTZ concentrations in plasma and excretion into the urine for healthy subjects and CHF patients. Data from healthy subjects receiving 100\u2009mg of oral HCTZ were supplemented with additional plasma concentration and urinary excretion versus time data published in the literature following administration of oral HCTZ doses ranging from 10 to 500\u2009mg to healthy subjects or patients with renal failure, CHF or hypertension. A two\u2010compartment model with first\u2010order oral absorption, using a Weibull function, and first\u2010order elimination best described HCTZ PK. Creatinine clearance (<jats:italic>CL<\/jats:italic><jats:sub>CR<\/jats:sub>) was a statistically significant predictor of renal clearance (<jats:italic>CL<\/jats:italic><jats:sub>R<\/jats:sub>). Non\u2010renal clearance was estimated to be 2.44\u2009l\/h, <jats:italic>CL<\/jats:italic><jats:sub>R<\/jats:sub> was 18.3\u2009l\/h and <jats:italic>T<\/jats:italic><jats:sub>1\/2,\u03b1<\/jats:sub> was 1.6\u2009h and <jats:italic>T<\/jats:italic><jats:sub>1\/2,\u03b2<\/jats:sub> was 14.8\u2009h for a typical individual with normal renal function (<jats:italic>CL<\/jats:italic><jats:sub>CR<\/jats:sub>\u2009=\u2009120\u2009ml\/min). However, <jats:italic>CL<\/jats:italic><jats:sub>R<\/jats:sub> was reduced to 10.5, 5.47 and 2.70\u2009l\/h in mild (<jats:italic>CL<\/jats:italic><jats:sub>CR<\/jats:sub>\u2009=\u200980\u2009ml\/min), moderate (<jats:italic>CL<\/jats:italic><jats:sub>CR<\/jats:sub>\u2009=\u200950\u2009ml\/min) and severe (<jats:italic>CL<\/jats:italic><jats:sub>CR<\/jats:sub>\u2009=\u200930\u2009ml\/min) renal impairment, respectively. Model diagnostics helped to demonstrate that the population PK model reasonably predicts the rate of urinary HCTZ excretion over time using dosing history and estimated <jats:italic>CL<\/jats:italic><jats:sub>CR<\/jats:sub>, allowing for the convenient assessment of PK\u2013PD relationships for HCTZ when given alone or in combination with other agents used to treat fluid overload conditions. Copyright \u00a9 2013 John Wiley &amp; Sons, Ltd.<\/jats:p>","DOI":"10.1002\/bdd.1863","type":"journal-article","created":{"date-parts":[[2013,10,12]],"date-time":"2013-10-12T01:01:34Z","timestamp":1381539694000},"page":"527-539","source":"Crossref","is-referenced-by-count":20,"title":["Population\u2010based meta\u2010analysis of hydrochlorothiazide pharmacokinetics"],"prefix":"10.1002","volume":"34","author":[{"given":"Scott A.","family":"Van Wart","sequence":"first","affiliation":[{"name":"Institute for Clinical Pharmacodynamics  Latham NY USA"},{"name":"Department of Pharmaceutical Sciences University at Buffalo, State University of New York  Buffalo NY USA"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Susan E.","family":"Shoaf","sequence":"additional","affiliation":[{"name":"Otsuka Pharmaceutical Development and Commercialization, Inc.  Rockville MD USA"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Suresh","family":"Mallikaarjun","sequence":"additional","affiliation":[{"name":"Otsuka Pharmaceutical Development and Commercialization, Inc.  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