{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,1,8]],"date-time":"2026-01-08T04:26:22Z","timestamp":1767846382936,"version":"3.49.0"},"reference-count":64,"publisher":"Wiley","issue":"11","license":[{"start":{"date-parts":[[2020,6,17]],"date-time":"2020-06-17T00:00:00Z","timestamp":1592352000000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/onlinelibrary.wiley.com\/termsAndConditions#vor"}],"content-domain":{"domain":["accp1.onlinelibrary.wiley.com"],"crossmark-restriction":true},"short-container-title":["The Journal of Clinical Pharma"],"published-print":{"date-parts":[[2020,11]]},"abstract":"<jats:title>Abstract<\/jats:title><jats:p>Cyclosporine is a primary drug in transplant immunosuppression regimens. It has a narrow therapeutic index and variable pharmacokinetic behavior. This study aimed to develop a population pharmacokinetic model of cyclosporine in Malaysian renal transplant recipients as well as to evaluate the performances of different methodsfor handling missing doses. A total of 2804 concentrationts predose and 2 hours after doses were collected retrospectively from 113 renal transplant patients on cyclosporine in Penang General Hospital. Model structure and pharmacokinetic parameters were estimated using nonlinear mixed\u2010effects modeling software. Missing doses were handled using different methods to evaluate their performance. Covariate analysis was performed using stepwise forward addition (<jats:italic>P<\/jats:italic>&lt; .05) followed by backward elimination (<jats:italic>P<\/jats:italic>&lt; .001). Prediction\u2010corrected visual predictive check and sampling\u2010importance resampling methods were used to validate the final model. A 1\u2010compartment model with first\u2010order absorption and elimination best fitted the data. All methods to handle missing doses performed well with the missing dose method being superior to other methods and thus was applied in the final model. Cyclosporine clearance (CL\/F) was estimated as 15.1 L\/h, and volume of distribution (V\/F) was 108 L. Postoperative time, sex, and calcium channel blockers were identified as significant covariates on CL\/F, whereas sex and cholesterol level were identified as significant covariates on V\/F. This is the first population pharmacokinetic model developed in Malaysian renal transplant patients using a large sample with an evaluation of different methods to handle missing doses in less informative conventional therapeutic drug\u2010monitoring data.<\/jats:p>","DOI":"10.1002\/jcph.1670","type":"journal-article","created":{"date-parts":[[2020,6,17]],"date-time":"2020-06-17T09:36:44Z","timestamp":1592386604000},"page":"1474-1482","update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":6,"title":["Population Pharmacokinetic Modeling of Cyclosporine Among Malaysian Renal Transplant Patients: An Evaluation of Methods to Handle Missing Doses in Conventional Drug\u2010Monitoring Data"],"prefix":"10.1002","volume":"60","author":[{"ORCID":"https:\/\/orcid.org\/0000-0003-4676-1334","authenticated-orcid":false,"given":"Orwa","family":"Albitar","sequence":"first","affiliation":[{"name":"School of Pharmaceutical Sciences Universiti Sains Malaysia Penang Malaysia"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Rama","family":"Ballouze","sequence":"additional","affiliation":[{"name":"Advanced Medical and Dental Institute Universiti Sains Malaysia Penang Malaysia"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Sabariah Noor","family":"Harun","sequence":"additional","affiliation":[{"name":"School of Pharmaceutical Sciences Universiti Sains Malaysia Penang Malaysia"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Dzul Azri","family":"Mohamed Noor","sequence":"additional","affiliation":[{"name":"School of Pharmaceutical Sciences Universiti Sains Malaysia Penang Malaysia"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Siti Maisharah","family":"Sheikh Ghadzi","sequence":"additional","affiliation":[{"name":"School of Pharmaceutical Sciences Universiti Sains Malaysia Penang Malaysia"}],"role":[{"role":"author","vocabulary":"crossref"}]}],"member":"311","published-online":{"date-parts":[[2020,6,17]]},"reference":[{"key":"e_1_2_10_2_1","doi-asserted-by":"publisher","DOI":"10.1111\/j.1600-6143.2009.02834.x"},{"key":"e_1_2_10_3_1","doi-asserted-by":"publisher","DOI":"10.1056\/NEJM200003023420901"},{"key":"e_1_2_10_4_1","first-page":"619","volume-title":"Pharmacology","author":"Tuteja S","year":"2014"},{"key":"e_1_2_10_5_1","first-page":"205","volume-title":"Clinical Pharmacokinetics","author":"Kiang TKL","year":"2017"},{"key":"e_1_2_10_6_1","doi-asserted-by":"publisher","DOI":"10.1111\/bcp.13431"},{"key":"e_1_2_10_7_1","doi-asserted-by":"publisher","DOI":"10.1208\/s12248-013-9500-8"},{"key":"e_1_2_10_8_1","doi-asserted-by":"publisher","DOI":"10.1038\/clpt.1988.42"},{"key":"e_1_2_10_9_1","doi-asserted-by":"publisher","DOI":"10.1056\/NEJMoa067411"},{"key":"e_1_2_10_10_1","doi-asserted-by":"publisher","DOI":"10.1155\/2020\/9872936"},{"key":"e_1_2_10_11_1","doi-asserted-by":"publisher","DOI":"10.2165\/00003088-199222060-00004"},{"key":"e_1_2_10_12_1","first-page":"183","volume-title":"Report of the Malaysian Dialysis and Transplant Registry","author":"Ghazali R","year":"2018"},{"key":"e_1_2_10_13_1","unstructured":"AbdAY AzizNA HassanY Bin SalihMRM GhazaliR.Therapeutic monitoring of cyclosporine in renal transplant patients. 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