1. J Antimicrob Chemother. 2018 Jun 1;73(6):1630-1638. doi: 10.1093/jac/dky078. Temocillin dosing in haemodialysis patients based on population pharmacokinetics of total and unbound concentrations and Monte Carlo simulations. Miranda Bastos AC(1)(2), Vandecasteele SJ(3), Spinewine A(2), Tulkens PM(1), Van Bambeke F(1). Author information: (1)Pharmacologie cellulaire et moléculaire, Louvain Drug Research Institute, Université catholique de Louvain, Brussels, Belgium. (2)Clinical Pharmacy Research Group, Louvain Drug Research Institute, Université catholique de Louvain, Brussels, Belgium. (3)Department of Nephrology and Infectious Diseases, AZ Sint-Jan Brugge-Oostende AV, Bruges, Belgium. Objectives: To develop a population model describing temocillin pharmacokinetics (PK) in patients undergoing haemodialysis and investigate how pharmacokinetic/pharmacodynamic (PD) targets can be met with different dosage regimens. Patients and methods: Sixteen patients received the currently licenced dosing of 1, 2 or 3 g of temocillin (total of 61 doses) corresponding to an inter-dialytic period of 20, 44 or 68 h, respectively, and a dialysis period of 4 h. A non-linear mixed-effects model was developed jointly for total and unbound temocillin serum concentrations. The performance of clinically feasible dosing regimens was evaluated using a 5000-subject Monte Carlo (MC) simulation for determining the highest MIC for which the PK/PD target of 40%ƒT>MIC would be reached in 90% of patients [probability of target attainment (PTA)]. This PK study was registered at ClinicalTrials.gov (NCT02285075). Results: Temocillin unbound and total serum concentrations (429 samples) were used to fit an open two-compartment model with non-linear albumin binding and first-order elimination. In addition to total body clearance, dialysis clearance was modelled using the Michaels function. The currently licenced dosing achieved a 90% PTA for an MIC up to 8 mg/L. A new temocillin dosage regimen was designed that would achieve a 90% PTA for an MIC of 16 mg/L (MIC90 of target organisms) adjusted to patient weight and inter-dialytic period. Conclusions: Currently licensed dosage regimen is suboptimal for MICs >8 mg/L (frequently found in clinical isolates). Model-based simulations allowed suggestion of a new dosage regimen with improved probability of microbiological success, applicability in routine clinical practice and more appropriate for empirical therapy. DOI: 10.1093/jac/dky078 PMID: 29579214