{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2025,6,6]],"date-time":"2025-06-06T08:10:37Z","timestamp":1749197437390},"reference-count":48,"publisher":"Ovid Technologies (Wolters Kluwer Health)","issue":"6","content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":[],"published-print":{"date-parts":[[2020,12]]},"abstract":"<jats:sec>\n            <jats:title>Background:<\/jats:title>\n            <jats:p>Theophylline, a xanthine derivative drug, is used for the treatment of respiratory diseases, such as asthma, and is primarily eliminated by hepatic metabolism. There is marked interindividual variability in theophylline clearance. Therefore, the aim of this study was to evaluate the influence of chronic hepatitis (CH), liver cirrhosis (LC), and other covariates on theophylline clearance by population pharmacokinetic (PPK) analysis.<\/jats:p>\n          <\/jats:sec>\n          <jats:sec>\n            <jats:title>Methods:<\/jats:title>\n            <jats:p>The authors retrospectively obtained 496 trough concentrations of theophylline at steady state from 226 adult patients with bronchial asthma. The liver functions of the patients were classified into 3 categories: normal hepatic function, CH, and LC. The PPK analysis was performed using the NONMEM program. CH, LC, age, smoking status, coadministration of clarithromycin (CAM), and sex were considered as covariates that affected theophylline clearance.<\/jats:p>\n          <\/jats:sec>\n          <jats:sec>\n            <jats:title>Results:<\/jats:title>\n            <jats:p>Theophylline clearance (CL\/F per kg) was significantly influenced by CH, LC, smoking, and CAM. The final model of theophylline clearance was as follows: CL\/F (L\/h\u00b7kg<jats:sup>\u22121<\/jats:sup>) = 0.0484 \u00d7 1.40<jats:sup>SMK<\/jats:sup> \u00d7 0.861<jats:sup>CAM<\/jats:sup> \u00d7 0.889<jats:sup>CH<\/jats:sup> \u00d7 0.557<jats:sup>LC<\/jats:sup>. Smoking is a well-known factor that markedly enhances CL\/F through the induction of CYP1A enzymes, whereas CAM has been reported to inhibit CYP3A4. The final model for hepatic function showed that CL\/F in CH and LC patients was 0.043 and 0.027 L\/h\/kg, respectively, and it was lower than that in patients with normal hepatic function. As theophylline clearance depends on intrinsic hepatic clearance, lower CL\/F in patients with LC than in those with CH may be due to a decrease in the metabolic enzymatic capability of LC patients.<\/jats:p>\n          <\/jats:sec>\n          <jats:sec>\n            <jats:title>Conclusions:<\/jats:title>\n            <jats:p>Differences exist in theophylline clearance between CH and LC patients as per the PPK analysis.<\/jats:p>\n          <\/jats:sec>","DOI":"10.1097\/ftd.0000000000000787","type":"journal-article","created":{"date-parts":[[2020,7,23]],"date-time":"2020-07-23T05:01:33Z","timestamp":1595480493000},"page":"829-834","source":"Crossref","is-referenced-by-count":4,"title":["Differences in Theophylline Clearance Between Patients With Chronic Hepatitis and Those With Liver Cirrhosis"],"prefix":"10.1097","volume":"42","author":[{"given":"Yasuo","family":"Kurata","sequence":"first","affiliation":[{"name":"Department of Pharmacy, Fukuoka City Hospital, Fukuoka City Hospital Organization, Local Incorporated Administrative Agency; and"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Shota","family":"Muraki","sequence":"additional","affiliation":[{"name":"Department of Clinical Pharmacokinetics, Graduate School of Kyushu University, Fukuoka, Japan."}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Yushi","family":"Kashihara","sequence":"additional","affiliation":[{"name":"Department of Clinical Pharmacokinetics, Graduate School of Kyushu University, Fukuoka, Japan."}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Takeshi","family":"Hirota","sequence":"additional","affiliation":[{"name":"Department of Clinical Pharmacokinetics, Graduate School of Kyushu University, Fukuoka, Japan."}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Hiroshi","family":"Araki","sequence":"additional","affiliation":[{"name":"Department of Pharmacy, Fukuoka City Hospital, Fukuoka City Hospital Organization, Local Incorporated Administrative Agency; and"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Ichiro","family":"Ieiri","sequence":"additional","affiliation":[{"name":"Department of Clinical Pharmacokinetics, Graduate School of Kyushu University, Fukuoka, Japan."}],"role":[{"role":"author","vocabulary":"crossref"}]}],"member":"276","reference":[{"key":"R1-20230814","doi-asserted-by":"crossref","first-page":"518","DOI":"10.1164\/ajrccm\/147.3.518","article-title":"Theophylline-an immunomodulatory role in asthma?","volume":"147","author":"Ward","year":"1993","journal-title":"Am Rev Respir Dis."},{"key":"R2-20230814","doi-asserted-by":"crossref","first-page":"1907","DOI":"10.1164\/ajrccm.151.6.7767539","article-title":"Immunomodulation by theophylline in asthma: demonstration by withdrawal of therapy","volume":"151","author":"Kidney","year":"1995","journal-title":"Am J Respir Crit Care Med."},{"key":"R3-20230814","doi-asserted-by":"crossref","first-page":"579","DOI":"10.1183\/09031936.94.07030579","article-title":"Theophylline in the management of asthma: time for reappraisal?","volume":"7","author":"Barnes","year":"1994","journal-title":"Eur Respir J."},{"key":"R4-20230814","doi-asserted-by":"crossref","first-page":"495","DOI":"10.2165\/00003088-199325060-00007","article-title":"Theophylline target concentration in severe airways obstruction\u201410 or 20 mg\/L? 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