{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,1,12]],"date-time":"2026-01-12T13:39:15Z","timestamp":1768225155626,"version":"3.49.0"},"reference-count":36,"publisher":"MDPI AG","issue":"1","license":[{"start":{"date-parts":[[2026,1,12]],"date-time":"2026-01-12T00:00:00Z","timestamp":1768176000000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"name":"Ministry of Science, Technological Development and Innovation, Republic of Serbia","award":["451-03-136\/2025-03\/200161"],"award-info":[{"award-number":["451-03-136\/2025-03\/200161"]}]},{"name":"Ministry of Science, Technological Development and Innovation, Republic of Serbia","award":["451-03-137\/2025-03\/200161"],"award-info":[{"award-number":["451-03-137\/2025-03\/200161"]}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["Pharmaceutics"],"abstract":"<jats:p>Background\/Objectives: Cyclosporine A (CsA) is a key immunosuppressant in post-transplantation therapy protocol characterized by large interindividual and intraindividual pharmacokinetic (PK) variability and a narrow therapeutic range necessitating therapeutic drug monitoring (TDM) to prevent graft rejection and minimize side effects. TDM data can be used for developing PK models with the objective of identification and quantification of variability factors that contribute to the differences in CsA concentrations. Methods: Retrospectively collected data from medical records of 58 patients (children and young adults) regarding CsA blood concentrations, concomitant medications, and laboratory findings of significance were used for the population PK model development in NONMEM\u00ae (version 7.5) with first-order conditional estimation method with interaction (FOCE-I). Simulation of the concentrations and area under the curve (AUC) was performed in the web application e-campsis\u00ae. RStudio (version 4.5.0) was used for the purpose of descriptive statistics analysis and graphs plotting. Results: A one-compartment model with first-order absorption and elimination best described the data. Value of clearance (CL\/F) was estimated to be 15 L\/h, and volume of distribution (V\/F) was 71.1 L for a typical patient weighing 40 kg. Interindividual variability (IIV) on CL\/F and V\/F was 34.91% and 43.05%, respectively. Interoccasional variability (IOV) was 12.25%. Body weight (WT) was introduced allometrically on CL\/F and V\/F, with the estimated exponent of 0.89 for CL\/F and 1 (fixed) for V\/F. According to the final model, CL\/F decreases with increasing haemoglobin (HGB) value. A difference of almost 22.5% in CL\/F was observed among patients\u2019 HGB values reported in the study. Conclusions: Our findings indicate that HGB levels significantly influence CsA PK, particularly minimum concentration (Cmin), highlighting the importance of regular HGB levels monitoring together with CsA levels.<\/jats:p>","DOI":"10.3390\/pharmaceutics18010099","type":"journal-article","created":{"date-parts":[[2026,1,12]],"date-time":"2026-01-12T10:25:23Z","timestamp":1768213523000},"page":"99","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":0,"title":["Population Pharmacokinetics Model of Cyclosporin A in Children and Young Adult Renal Transplant Patients: Focus on Haemoglobin Contribution to Exposure Variability"],"prefix":"10.3390","volume":"18","author":[{"ORCID":"https:\/\/orcid.org\/0000-0003-2021-9897","authenticated-orcid":false,"given":"Ma\u0161a","family":"Roganovi\u0107","sequence":"first","affiliation":[{"name":"Department of Pharmacokinetics and Clinical Pharmacy, Faculty of Pharmacy, University of Belgrade, 11221 Belgrade, Serbia"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0009-0004-7600-2851","authenticated-orcid":false,"given":"Mirjana","family":"Cvetkovi\u0107","sequence":"additional","affiliation":[{"name":"Department of Nephrology, Dialysis, and Transplantation, University Children\u2019s Hospital, 11000 Belgrade, Serbia"},{"name":"Faculty of Medicine, University of Belgrade, 11000 Belgrade, Serbia"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0009-0006-0600-9454","authenticated-orcid":false,"given":"Ivana","family":"Gojkovi\u0107","sequence":"additional","affiliation":[{"name":"Department of Nephrology, Dialysis, and Transplantation, University Children\u2019s Hospital, 11000 Belgrade, Serbia"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-1070-8155","authenticated-orcid":false,"given":"Brankica","family":"Spasojevi\u0107","sequence":"additional","affiliation":[{"name":"Department of Nephrology, Dialysis, and Transplantation, University Children\u2019s Hospital, 11000 Belgrade, Serbia"},{"name":"Faculty of Medicine, University of Belgrade, 11000 Belgrade, Serbia"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-6267-7509","authenticated-orcid":false,"given":"Marija","family":"Jovanovi\u0107","sequence":"additional","affiliation":[{"name":"Department of Pharmacokinetics and Clinical Pharmacy, Faculty of Pharmacy, University of Belgrade, 11221 Belgrade, Serbia"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-5088-5976","authenticated-orcid":false,"given":"Branislava","family":"Miljkovi\u0107","sequence":"additional","affiliation":[{"name":"Department of Pharmacokinetics and Clinical Pharmacy, Faculty of Pharmacy, University of Belgrade, 11221 Belgrade, Serbia"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-9676-5785","authenticated-orcid":false,"given":"Katarina","family":"Vu\u010di\u0107evi\u0107","sequence":"additional","affiliation":[{"name":"Department of Pharmacokinetics and Clinical Pharmacy, Faculty of Pharmacy, University of Belgrade, 11221 Belgrade, Serbia"}],"role":[{"role":"author","vocabulary":"crossref"}]}],"member":"1968","published-online":{"date-parts":[[2026,1,12]]},"reference":[{"key":"ref_1","doi-asserted-by":"crossref","first-page":"165","DOI":"10.2165\/00148581-200709030-00005","article-title":"Calcineurin Inhibitors in Pediatric Renal Transplant Recipients","volume":"9","author":"Filler","year":"2007","journal-title":"Paediatr. 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