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This study characterized the pharmacokinetic (PK) profile of atacicept using a population PK model and identified covariates explaining the PK variability. Total atacicept concentrations from a phase I study in healthy volunteers and two phase II studies in patients with SLE, using subcutaneous administration, were modeled using a quasi\u2010steady\u2010state approximation of the target\u2010mediated drug disposition model with first\u2010order absorption. The model included 3640 serum atacicept concentration records from 37 healthy volunteers and 503 patients with SLE and described total atacicept concentrations of the three trials, providing precise estimates of all parameters. Body weight and baseline BLyS concentration were the only statistically significant covariates, whereas no differences were found between patients and healthy volunteers. Apparent clearance and volume of the central compartment increased with body weight and initial target concentration increased with baseline BLyS. The change on atacicept exposure was moderate, with a difference in area under the curve compared with the median of 20%\u201332% for body weight, and 7%\u201318% for BLyS. Therefore, the effects of these covariates on atacicept exposure are not expected to be clinically relevant. The model described the complete total atacicept concentration\u2013time profiles without finding any differences between healthy subjects and patients with SLE and supports the 150\u2009mg once weekly dose for further trials.<\/jats:p>","DOI":"10.1002\/psp4.12982","type":"journal-article","created":{"date-parts":[[2023,6,19]],"date-time":"2023-06-19T04:28:55Z","timestamp":1687148935000},"page":"1157-1169","update-policy":"http:\/\/dx.doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":1,"title":["Population pharmacokinetics of atacicept in systemic lupus erythematosus: An analysis of three clinical trials"],"prefix":"10.1002","volume":"12","author":[{"given":"Maria","family":"Pitsiu","sequence":"first","affiliation":[{"name":"Quantitative Pharmacology and Pharmacometrics ICON Clinical Research UK Ltd  Marlow UK"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"\u00d6zkan","family":"Yalkinoglu","sequence":"additional","affiliation":[{"name":"Translational Medicine the healthcare business of Merck KGaA  Darmstadt Germany"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Colm","family":"Farrell","sequence":"additional","affiliation":[{"name":"Quantitative Pharmacology and Pharmacometrics ICON Clinical Research UK Ltd  Marlow UK"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Pascal","family":"Girard","sequence":"additional","affiliation":[{"name":"Merck Institute of Pharmacometrics, Lausanne, Switzerland, an Affiliate of Merck KGaA, Darmstadt, Germany Ares Trading S.A.  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