Farmakometri
Vi utvecklar och använder matematiska modeller för att förstå läkemedels- och sjukdomsmekanismer och för att optimera läkemedelsutveckling och terapi.
Vår forskning
Farmakometrisk forskning fokuserar på s k icke-linjära, blandade modeller, även kallade populationsmodeller. Modellerna vi utvecklar och använder beskriver tidsvarierande data, som oftast kommer från kliniska prövningar. Dessa modeller har en basstruktur som beskriver det underliggande systemet och en uppsättning hierarkiska variabilitetskomponenter, som beskriver variationer mellan individer, mellan tillfällen och mellan observationer.
Forskning inom farmakometrisk gruppen är uppdelad i fyra huvudområden:
- Vi utvecklar och utvärderar metoder för effektiv och robust modellbyggnad. Detta inbegriper utveckling av estimeringsalgoritmer, metoder för modelldiagnos och sekventiella förfaranden för modellbyggnad. Vi delar med oss av denna forskning genom "open source" mjukvara.
- Vi utvecklar plattformsmodeller för användning i specifika terapeutiska områden eller för särskilda terapeutiska / farmakologiska principer. Dessa modeller beskriver tidsförloppet hos en biomarkör eller ett system av biomarkörer under friska, sjuka och / eller provocerade tillstånd.
- Vi använder modeller för att utforma studier, besluta om doseringsstrategier och andra utvecklingsbeslut.
- Vi analyserar doskoncentrationsresponsdata från försök för att förstå terapier med existerande läkemedel i syfte att möjliggöra förbättrad terapi.
Nyheter
Kalendarium
- Inga kommande evenemang för tillfället
Publikationer
-
Yin, Anyue; van Hasselt, Johan G. C.; Guchelaar, Henk-Jan; Friberg, Lena; Moes, Dirk Jan A. R.
Anti-cancer treatment schedule optimization based on tumor dynamics modelling incorporating evolving resistance
2022
-
De Jager, Veronique; Gupte, Nikhil; Nunes, Silvia; Barnes, Grace L.; Van Wijk, Rob C; Mostert, Joni; Dorman, Susan E.; Abulfathi, Ahmed A.; Upton, Caryn M.; Faraj, Alan; Nuermberger, Eric L.; Lamichhane, Gyanu; Svensson, Elin; Simonsson, Ulrika S. H.; Diacon, Andreas H.; Dooley, Kelly E.
Early Bactericidal Activity of Meropenem plus Clavulanate (with or without Rifampin) for Tuberculosis: The COMRADE Randomized, Phase 2A Clinical Trial
2022
-
Brem, Jürgen; Panduwawala, Tharindi; Hansen, Jon Ulf; Hewitt, Joanne; Liepins, Edgars; Donets, Pawel; Espina, Laura; Farley, Alistair J M; Shubin, Kirill; Campillos, Gonzalo Gomez; Kiuru, Paula; Shishodia, Shifali; Krahn, Daniel; Leśniak, Robert K; Schmidt Adrian, Juliane; Calvopiña, Karina; Turrientes, María-Carmen; Kavanagh, Madeline E; Lubriks, Dmitrijs; Hinchliffe, Philip; Langley, Gareth W; Aboklaish, Ali F; Eneroth, Anders; Backlund, Maria; Baran, Andrei G; Nielsen, Elisabet I.; Speake, Michael; Kuka, Janis; Robinson, John; Grinberga, Solveiga; Robinson, Lindsay; McDonough, Michael A; Rydzik, Anna M; Leissing, Thomas M; Jimenez-Castellanos, Juan Carlos; Avison, Matthew B; Da Silva Pinto, Solange; Pannifer, Andrew D; Martjuga, Marina; Widlake, Emma; Priede, Martins; Hopkins Navratilova, Iva; Gniadkowski, Marek; Belfrage, Anna Karin; Brandt, Peter; Yli-Kauhaluoma, Jari; Bacque, Eric; Page, Malcolm G P; Björkling, Fredrik; Tyrrell, Jonathan M; Spencer, James; Lang, Pauline A; Baranczewski, Pawel; Cantón, Rafael; McElroy, Stuart P; Jones, Philip S; Baquero, Fernando; Suna, Edgars; Morrison, Angus; Walsh, Timothy R; Schofield, Christopher J
Imitation of β-lactam binding enables broad-spectrum metallo-β-lactamase inhibitors
2022
-
Nutman, Amir; Temkin, Elizabeth; Lellouche, Jonathan; Rakovitsky, Nadya; Hameir, Amichay; Daikos, George; Durante-Mangoni, Emanuele; Pavleas, Ioannis; Dishon, Yael; Petersiel, Neta; Yahav, Dafna; Eliakim, Noa; Bernardo, Mariano; Iossa, Domenico; Friberg, Lena; Theuretzbacher, Ursula; Leibovici, Leonard; Paul, Mical; Carmeli, Yehuda
In vivo fitness of carbapenem-resistant Acinetobacter baumannii strains in murine infection is associated with treatment failure in human infections
2022
-
Frenk, Sammy; Temkin, Elizabeth; Lurie-Weinberger, Mor N.; Keren-Paz, Alona; Rov, Reut; Rakovitsky, Nadya; Wullfhart, Liat; Nutman, Amir; Daikos, George L.; Skiada, Anna; Durante-Mangoni, Emanuele; Benattar, Yael Dishon; Bitterman, Roni; Yahav, Dafna; Daitch, Vered; Bernardo, Mariano; Iossa, Domenico; Zusman, Oren; Friberg, Lena; Mouton, Johan W.; Theuretzbacher, Ursula; Leibovici, Leonard; Geffen, Yuval; Gershon, Rina; Paul, Mical; Carmeli, Yehuda
Large-scale WGS of carbapenem-resistant Acinetobacter baumannii isolates reveals patterns of dissemination of ST clades associated with antibiotic resistance
2022
-
Grisic, Ana-Marija; Xiong, Wenyuan; Tanneau, Lénaïg; Jönsson, Siv; Friberg, Lena; Karlsson, Mats; Dai, Haiqing; Zheng, Jenny; Girard, Pascal; Khandelwal, Akash
Model-Based Characterization of the Bidirectional Interaction Between Pharmacokinetics and Tumor Growth Dynamics in Patients with Metastatic Merkel Cell Carcinoma Treated with Avelumab
2022
-
Koele, Simon E.; van Beek, Stijn W.; Maartens, Gary; Brust, James C. M.; Svensson, Elin
Optimized Loading Dose Strategies for Bedaquiline When Restarting Interrupted Drug-Resistant Tuberculosis Treatment
2022
-
Sasaki, Tomohiro; Svensson, Elin; Wang, Xiaofeng; Wang, Yanlin; Hafkin, Jeffrey; Karlsson, Mats; Mallikaarjun, Suresh
Population Pharmacokinetic and Concentration-QTc Analysis of Delamanid in Pediatric Participants with Multidrug-Resistant Tuberculosis
2022
-
Swartling, Maria; Smekal, Anna-Karin; Furebring, Mia; Lipcsey, Miklós; Jönsson, Siv; Nielsen, Elisabet I.
Population pharmacokinetics of cefotaxime in intensive care patients
2022
-
Litjens, Carlijn H. C.; Verscheijden, Laurens F. M.; Bolwerk, Celine; Greupink, Rick; Koenderink, Jan B.; van den Broek, Petra H. H.; van den Heuvel, Jeroen J. M. W.; Svensson, Elin; Boeree, Martin J.; Magis-Escurra, Cecile; Hoefsloot, Wouter; van Crevel, Reinout; van Laarhoven, Arjan; van Ingen, Jakko; Kuipers, Saskia; Ruslami, Rovina; Burger, David M.; Russel, Frans G. M.; Aarnoutse, Rob E.; Te Brake, Lindsey H. M.
Prediction of Moxifloxacin Concentrations in Tuberculosis Patient Populations by Physiologically Based Pharmacokinetic Modeling
2022
-
Gkoufa, Aikaterini; Sou, Tomas; Karaiskos, Ilias; Routsi, Christina; Lin, Yu-Wei; Psichogiou, Mina; Zakynthinos, Spyros; Giamarellou, Helen; Li, Jian; Friberg, Lena
Pulmonary and systemic pharmacokinetics of colistin methanesulfonate (CMS) and formed colistin following nebulisation of CMS among patients with ventilator-associated pneumonia
2022
-
Ruth, Mike Marvin; Raaijmakers, Jelmer; van den Hombergh, Erik; Aarnoutse, Rob; Svensson, Elin; Susanto, Budi Octasari; Simonsson, Ulrika S. H.; Wertheim, Heiman; Hoefsloot, Wouter; van Ingen, Jakko
Standard therapy of Mycobacterium avium complex pulmonary disease shows limited efficacy in an open source hollow fibre system that simulates human plasma and epithelial lining fluid pharmacokinetics
2022
-
van Beek, Stijn W.; ter Heine, Rob; Alffenaar, Jan-Willem C.; Magis-Escurra, Cecile; Aarnoutse, Rob E.; Svensson, Elin M.
A Model-Informed Method for the Purpose of Precision Dosing of Isoniazid in Pulmonary Tuberculosis
2021
-
Bukkems, Vera E.; Post, Teun M.; Colbers, Angela P.; Burger, David M.; Svensson, Elin
A population pharmacokinetics analysis assessing the exposure of raltegravir once-daily 1200 mg in pregnant women living with HIV
2021
-
Germovsek, Eva; Hansson, Anna; Karlsson, Mats O.; Westin, Ake; Soons, Paul A.; Vermeulen, An; Kjellsson, Maria C.
A Time-to-Event Model Relating Integrated Craving to Risk of Smoking Relapse Across Different Nicotine Replacement Therapy Formulations
2021
-
Sonawane, Vidhisha V.; Ruth, Mike M.; Pennings, Lian J.; Svensson, Elin; Wertheim, Heiman F. L.; Hoefsloot, Wouter; van Ingen, Jakko
An In Vitro Perspective on What Individual Antimicrobials Add to Mycobacterium avium Complex Therapies
2021
-
Wellhagen, Gustaf; Ueckert, Sebastian; Kjellsson, Maria C.; Karlsson, Mats
An Item Response Theory-Informed Strategy to Model Total Score Data from Composite Scales
2021
-
Becker, Katja; Cao, Sha; Nilsson, Anna; Erlandsson, Maria; Hotop, Sven-Kevin; Kuka, Janis; Hansen, Jon; Haldimann, Klara; Grinberga, Solveiga; Berruga Fernández, Talia; Huseby, Douglas L; Shariatgorji, Reza; Lindmark, Evelina; Platzack, Bjorn; Bottger, Erik C.; Crich, David; Friberg, Lena; Lundberg, Carina Vingsbo; Hughes, Diarmaid; Broenstrup, Mark; Andrén, Per E.; Liepinsh, Edgars; Hobbie, Sven N.
Antibacterial activity of apramycin at acidic pH warrants wide therapeutic window in the treatment of complicated urinary tract infections and acute pyelonephritis
2021
-
Cam, Henrik; Kempen, Thomas Gerardus Hendrik; Eriksson, Helena; Abdulreda, Kanar; Franzon, Kristin; Gillespie, Ulrika
Assessment of requests for medication-related follow-up after hospital discharge, and the relation to unplanned hospital revisits, in older patients: a multicentre retrospective chart review
2021
-
Lyauk, Yassine Kamal; Jonker, Daniel M.; Hooker, Andrew; Lund, Trine Meldgaard; Karlsson, Mats
Bounded Integer Modeling of Symptom Scales Specific to Lower Urinary Tract Symptoms Secondary to Benign Prostatic Hyperplasia
2021
-
Buatois, Simon; Ueckert, Sebastian; Frey, Nicolas; Retout, Sylvie; Mentre, France
cLRT-Mod: An efficient methodology for pharmacometric model-based analysis of longitudinal phase II dose finding studies under model uncertainty
2021
-
Wellhagen, Gustaf J.; Karlsson, Mats O.; Kjellsson, Maria C.
Comparison of Precision and Accuracy of Five Methods to Analyse Total Score Data
2021
-
Wasmann, Roeland E.; Svensson, Elin; Walker, A. Sarah; Clements, Michelle N.; Denti, Paolo
Constructing a representative in-silico population for paediatric simulations: Application to HIV-positive African children
2021
-
Sulku, Johanna; Bröms, Kristina; Högman, Marieann; Janson, Christer; Lisspers, Karin; Malinovschi, Andrei; Melhus, Håkan; Ställberg, Björn; Nielsen, Elisabet I.
Critical inhaler technique errors in Swedish patients with COPD: a cross-sectional study analysing video-recorded demonstrations
2021
-
Chen, Chao; Jönsson, Siv; Yang, Shuying; Plan, Elodie L.; Karlsson, Mats
Detecting placebo and drug effects on Parkinson's disease symptoms by longitudinal item-score models
2021
-
Abdelwahab, Mahmoud Tareq; Court, Richard; Everitt, Daniel; Diacon, Andreas H.; Dawson, Rodney; Svensson, Elin; Maartens, Gary; Denti, Paolo
Effect of Clofazimine Concentration on QT Prolongation in Patients Treated for Tuberculosis
2021
-
van Doorn, Leni; van Rosmalen, Mandy M.; van der Deure, Wendy M.; Oomen-de Hoop, Esther; Porrazzo, Robert; Wijngaard, Sophie M.; Boere, Ingrid A.; Veenstra, Paola; Ibrahim, Eman; de Bruijn, Peter; Friberg, Lena; Koolen, Stijn L. W.; Mathijssen, Ron H. J.; Jager, Agnes
Effect of Scalp Cooling on the Pharmacokinetics of Paclitaxel
2021
-
Kempen, Thomas; Bertilsson, Maria; Hadziosmanovic, Nermin; Lindner, Karl-Johan; Melhus, Håkan; Nielsen, Elisabet I.; Sulku, Johanna; Gillespie, Ulrika
Effects of Hospital-Based Comprehensive Medication Reviews Including Postdischarge Follow-up on Older Patients' Use of Health Care: A Cluster Randomized Clinical Trial
2021
-
Becker, Katja; Aranzana-Climent, Vincent; Cao, Sha; Nilsson, Anna; Shariatgorji, Reza; Haldimann, Klara; Platzack, Bjorn; Hughes, Diarmaid; Andrén, Per E.; Bottger, Erik C.; Friberg, Lena E.; Hobbie, Sven N.
Efficacy of EBL-1003 (apramycin) against Acinetobacter baumannii lung infections in mice
2021
-
Daitch, Vered; Paul, Mical; Daikos, George L.; Durante-Mangoni, Emanuele; Yahav, Dafna; Carmeli, Yehuda; Benattar, Yael Dishon; Skiada, Anna; Andini, Roberto; Eliakim-Raz, Noa; Nutman, Amir; Zusman, Oren; Antoniadou, Anastasia; Cavezza, Giusi; Adler, Amos; Dickstein, Yaakov; Pavleas, Ioannis; Zampino, Rosa; Bitterman, Roni; Zayyad, Hiba; Koppel, Fidi; Zak-Doron, Yael; Levi, Inbar; Babich, Tanya; Turjeman, Adi; Ben-Zvi, Haim; Friberg, Lena; Mouton, Johan W.; Theuretzbacher, Ursula; Leibovici, Leonard
Excluded versus included patients in a randomized controlled trial of infections caused by carbapenem-resistant Gram-negative bacteria: relevance to external validity
2021
-
Tanneau, Lénaïg; Svensson, Elin; Rossenu, Stefaan; Karlsson, Mats
Exposure–safety analysis of QTc interval and transaminase levels following bedaquiline administration in patients with drug‐resistant tuberculosis
2021
-
Wicha, Sebastian G.; Martson, Anne-Grete; Nielsen, Elisabet I.; Koch, Birgit C. P.; Friberg, Lena; Alffenaar, Jan-Willem; Minichmayr, Iris
From Therapeutic Drug Monitoring to Model-Informed Precision Dosing for Antibiotic
2021
-
Cresswell, Fiona, V; Meya, David B.; Kagimu, Enock; Grint, Daniel; Te Brake, Lindsey; Kasibante, John; Martyn, Emily; Rutakingirwa, Morris; Quinn, Carson M.; Okirwoth, Micheal; Tugume, Lillian; Ssembambulidde, Kenneth; Musubire, Abdu K.; Bangdiwala, Ananta S.; Buzibye, Allan; Muzoora, Conrad; Svensson, Elin; Aarnoutse, Rob; Boulware, David R.; Elliott, Alison M.
High-Dose Oral and Intravenous Rifampicin for the Treatment of Tuberculous Meningitis in Predominantly Human Immunodeficiency Virus (HIV)-Positive Ugandan Adults: A Phase II Open-Label Randomized Controlled Trial
2021
-
Pieterman, E. D.; van den Berg, S.; van der Meijden, A.; Svensson, Elin; Bax, H. , I; de Steenwinkel, J. E. M.
Higher Dosing of Rifamycins Does Not Increase Activity against Mycobacterium tuberculosis in the Hollow-Fiber Infection Model
2021
-
Llanos-Paez, Carolina; Ambery, Claire; Yang, Shuying; Tabberer, Maggie; Beerahee, Misba; Plan, Elodie L.; Karlsson, Mats O.
Improved Decision-Making Confidence Using Item-Based Pharmacometric Model: Illustration with a Phase II Placebo-Controlled Trial
2021
-
Ueckert, Sebastian; Karlsson, Mats
Improved numerical stability for the bounded integer model
2021
-
te Brake, Lindsey H. M.; de Jager, Veronique; Narunsky, Kim; Vanker, Naadira; Svensson, Elin; Phillips, Patrick P. J.; Gillespie, Stephen H.; Heinrich, Norbert; Hoelscher, Michael; Dawson, Rodney; Diacon, Andreas H.; Aamoutse, Rob E.; Boeree, Martin J.
Increased bactericidal activity but dose-limiting intolerability at 50 mg.kg(-1) rifampicin
2021
-
Leohr, Jennifer; Kjellsson, Maria C.
Linking categorical models for prediction of pleasantness score using individual predictions of sweetness and creaminess: An advancement of categorical modeling
2021
-
Kim, Seongho; Hooker, Andrew; Shi, Yu; Kim, Grace Hyun J.; Wong, Weng Kee
Metaheuristics for pharmacometrics
2021
-
van Beek, Stijn W.; Svensson, Elin; Tiono, Alfred B.; Okebe, Joseph; D'Alessandro, Umberto; Goncalves, Bronner P.; Bousema, Teun; Drakeley, Chris; ter Heine, Rob
Model-based assessment of the safety of community interventions with primaquine in sub-Saharan Africa
2021
-
Rayner, Craig R.; Smith, Patrick F.; Andes, David; Andrews, Kayla; Derendorf, Hartmut; Friberg, Lena E.; Hanna, Debra; Lepak, Alex; Mills, Edward; Polasek, Thomas M.; Roberts, Jason A.; Schuck, Virna; Shelton, Mark J.; Wesche, David; Rowland-Yeo, Karen
Model-Informed Drug Development for Anti-Infectives: State of the Art and Future
2021
-
Sou, Tomás; Hansen, Jon; Liepinsh, Edgars; Backlund, Maria; Ercan, Onur; Grinberga, Solveiga; Cao, Sha; Giachou, Paraskevi; Petersson, Anna; Tomczak, Magdalena; Urbas, Malgorzata; Zabicka, Dorota; Vingsbo Lundberg, Carina; Hughes, Diarmaid; Hobbie, Sven N; Friberg, Lena
Model-Informed Drug Development for Antimicrobials: Translational PK and PK/PD Modeling to Predict an Efficacious Human Dose for Apramycin
2021
-
Krishnan, Sreenath M.; Friberg, Lena E.; Bruno, René; Beyer, Ulrich; Jin, Jin Y.; Karlsson, Mats O.
Multistate model for pharmacometric analyses of overall survival in HER2-negative breast cancer patients treated with docetaxel
2021
-
Wasmann, Roeland E.; Svensson, Elin; Schalkwijk, Stein J.; Brüggemann, Roger J.; ter Heine, Rob
Normal fat mass cannot be reliably estimated in typical pharmacokinetic studies
2021
-
Ibrahim, Moustafa M. A.; Redestad, Erik; Kjellsson, Maria C.
Optimal Designs for Model-Based Assessment of Insulin Sensitivity and Glucose Effectiveness.
2021
-
Garcia-Prats, Anthony J.; Svensson, Elin; Winckler, Jana; Draper, Heather R.; Fairlie, Lee; van der Laan, Louvina E.; Masenya, Masebole; Schaaf, H. Simon; Wiesner, Lubbe; Norman, Jennifer; Aarnoutse, Rob E.; Karlsson, Mats O.; Denti, Paolo; Hesseling, Anneke C.
Pharmacokinetics and safety of high-dose rifampicin in children with TB: the Opti-Rif trial
2021
-
Ryeznik, Yevgen; Sverdlov, Oleksandr; Svensson, Elin; Montepiedra, Grace; Hooker, Andrew; Wong, Weng Kee
Pharmacometrics meets statistics-A synergy for modern drug development
2021
-
Minichmayr, Iris K.; Karlsson, Mats O.; Jönsson, Siv
Pharmacometrics-Based Considerations for the Design of a Pharmacogenomic Clinical Trial Assessing Irinotecan Safety
2021
-
Friberg, Lena E.
Pivotal Role of Translation in Anti-Infective Development
2021
-
Sturkenboom, Marieke G. G.; Martson, Anne-Grete; Svensson, Elin; Sloan, Derek J.; Dooley, Kelly E.; van den Elsen, Simone H. J.; Denti, Paolo; Peloquin, Charles A.; Aarnoutse, Rob E.; Alffenaar, Jan-Willem C.
Population Pharmacokinetics and Bayesian Dose Adjustment to Advance TDM of Anti-TB Drugs
2021