Pharmacometrics
We develop and use mathematical models to understand drug and disease mechanisms, and to optimise drug development and therapy.
Our research
Pharmacometric research focuses on nonlinear mixed effects (”population”) models. Such models describe data, generally the response-time profiles observed in a clinical trial, by a basic model, accounting for the general structure of the underlying system, and a set of hierarchical variability components, accounting for variability between subjects, within subjects over time and remaining between observation variability.
Research at the pharmacometrics group is divided into four main areas:
- We develop and evaluate methods for efficient and robust model building. This involves development of estimation algorithms, methods for model diagnosis and sequential procedures for model building. The result of the research, when applicable, is made available as free software.
- We develop platform models for the use in specific therapeutic areas or particular therapeutic/ pharmacological principles. Such models may involve the time-course of a biomarker or a system of biomarkers during normal, diseased and/or provoked conditions.
- We utilize the developed models for the purpose of designing studies, deciding upon dosing strategies and other developmental decisions.
- We analyse dose-concentration-response data from trials to understand therapies with existing drugs with the aim of allowing improved therapy.
Faculty News
- Four thumbs up for SweDeliver summer internship at AstraZeneca
- SweDeliver's summer internships adding value to all parties
- Maria Kjellsson has been appointed Professor of Pharmacokinetics
- Christel Bergström: "Uppsala's Life science hub is at the highest international level"
- Paarkavi Udayakumar and Yuming Zhang win Best Poster Awards at CRS 2023
Department Calendar
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Half-time seminar: Artificial colonic mucus development as in vitro drug diffusion testing platform
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Half-time seminar: Drug delivery platform for optimal intestinal absorption of oral antibiotics
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New Horizons in Drug Delivery and Formulations 2023
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Half-time seminar: Influence of intra- and extracellular free drug concentrations in the human colon on local and systemic drug exposure
Group Publications
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de Jong, Karen; Damoiseaux, David; Pluim, Dick; Rosing, Hilde; Beijnen, Jos H.; van Thienen, Hans; Dorlo, Thomas P. C.; Huitema, Alwin D. R.; Amant, Frederic
High accumulation of nivolumab in human breast milk: A case report
2023
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Damoiseaux, David; Centanni, Daniel; Beijnen, Jos H.; Amant, Frédéric; Huitema, Alwin D. R.; Dorlo, Thomas P. C.
Predicting Chemotherapy Distribution into Breast Milk for Breastfeeding Women Using a Population Pharmacokinetic Approach
2023
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Chu, Wan-Yu; Dorlo, Thomas P. C.
Pyronaridine: a review of its clinical pharmacology in the treatment of malaria
2023
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Janssen, J. M.; Damoiseaux, D.; van Hasselt, J. G. C.; Amant, F. C. H.; van Calsteren, K.; Beijnen, J. H.; Huitema, A. D. R.; Dorlo, Thomas P. C.
Semi-physiological Enriched Population Pharmacokinetic Modelling to Predict the Effects of Pregnancy on the Pharmacokinetics of Cytotoxic Drugs
2023
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Mim, Sabiha R.; Hussein, Haneen; Vidadi, Samira; Leisegang, Rory; Karamchand, Sumanth; Rambiritch, Virendra; Cotton, Mark F.; Naidoo, Poobalan; Kjellsson, Maria C.
Optimal dosing of gliclazide-A model-based approach
2023
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Llanos-Paez, Carolina; Ambery, Claire; Yang, Shuying; Beerahee, Misba; Plan, Elodie L.; Karlsson, Mats O.
Joint longitudinal model-based meta-analysis of FEV1 and exacerbation rate in randomized COPD trials
2023
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Gafar, Fajri; Wasmann, Roeland E.; McIlleron, Helen M.; Aarnoutse, Rob E.; Schaaf, H. Simon; Marais, Ben J.; Agarwal, Dipti; Antwi, Sampson; Bang, Nguyen D.; Bekker, Adrie; Bell, David J.; Chabala, Chishala; Choo, Louise; Davies, Geraint R.; Day, Jeremy N.; Dayal, Rajeshwar; Denti, Paolo; Donald, Peter R.; Engidawork, Ephrem; Garcia-Prats, Anthony J.; Gibb, Diana; Graham, Stephen M.; Hesseling, Anneke C.; Heysell, Scott K.; Idris, Misgana I.; Kabra, Sushil K.; Kinikar, Aarti; Kumar, Agibothu K. Hemanth; Kwara, Awewura; Lodha, Rakesh; Magis-Escurra, Cecile; Martinez, Nilza; Mathew, Binu S.; Mave, Vidya; Mduma, Estomih; Mlotha-Mitole, Rachel; Mpagama, Stellah G.; Mukherjee, Aparna; Nataprawira, Heda M.; Peloquin, Charles A.; Pouplin, Thomas; Ramachandran, Geetha; Ranjalkar, Jaya; Roy, Vandana; Ruslami, Rovina; Shah, Ira; Singh, Yatish; Sturkenboom, Marieke G. G.; Svensson, Elin M.; Swaminathan, Soumya; Thatte, Urmila; Thee, Stephanie; Thomas, Tania A.; Tikiso, Tjokosela; Touw, Daan J.; Turkova, Anna; Velpandian, Thirumurthy; Verhagen, Lilly M.; Winckler, Jana L.; Yang, Hongmei; Yunivita, Vycke; Taxis, Katja; Stevens, Jasper; Alffenaar, Jan-Willem C.
Global estimates and determinants of antituberculosis drug pharmacokinetics in children and adolescents: a systematic review and individual patient data meta-analysis
2023
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Van der Heijden, Lisa T.; Nijstad, A. Laura; Uittenboogaard, Aniek; Beijnen, Jos H.; Dorlo, Thomas P. C.; Kaspers, Gertjan J. L.; Huitema, Alwin D. R.
Development of a Therapeutic Drug Monitoring Strategy for the Optimization of Vincristine Treatment in Pediatric Oncology Populations in Africa
2023
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Bukkems, Laura H.; Versloot, Olav; Cnossen, Marjon H.; Jönsson, Siv; Karlsson, Mats O.; Mathot, Ron A. A.; Fischer, Kathelijn
Association between Sports Participation, Factor VIII Levels and Bleeding in Hemophilia A
2023
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Eriksson, Jan; Emad, Reem A.; Lundqvist, Martin H.; Abrahamsson, Niclas; Kjellsson, Maria C.
Altered glucose-dependent secretion of glucagon and ACTH is associated with insulin resistance, assessed by population analysis
2023
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Bahnasawy, Salma M.; Skorup, Paul; Hanslin, Katja; Friberg, Lena; Lipcsey, Miklós; Nielsen, Elisabet I.
Predicting cytokine kinetics during sepsis; a modelling framework from a porcine sepsis model with live Escherichia coli
2023
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Singh, K. P.; Carvalho, A. C. C.; Centis, R.; D'Ambrosio, L.; Migliori, G. B.; Mpagama, S. G.; Nguyen, B. C.; Aarnoutse, R. E.; Aleksa, A.; van Altena, R.; Bhavani, P. K.; Bolhuis, M. S.; Borisov, S.; van't Boveneind-Vrubleuskaya, N.; Bruchfeld, J.; Caminero, J. A.; Carvalho, I.; Cho, J. G.; Forsman, L. Davies; Dedicoat, M.; Dheda, K.; Dooley, K.; Furin, J.; Garcia-Garcia, J. M.; Garcia-Prats, A.; Hesseling, A. C.; Heysell, S. K.; Hu, Y.; Kim, H. Y.; Manga, S.; Marais, B. J.; Margineanu, I.; Martson, A-G; Torrico, M. Munoz; Nataprawira, H. M.; Nunes, E.; Ong, C. W. M.; Otto-Knapp, R.; Palmero, D. J.; Peloquin, C. A.; Rendon, A.; Silva, D. Rossato; Ruslami, R.; Saktiawati, A. M. I.; Santoso, P.; Schaaf, H. S.; Seaworth, B.; Simonsson, Ulrika S. H.; Singla, R.; Skrahina, A.; Solovic, I.; Srivastava, S.; Stocker, S. L.; Stukenboom, M. G. G.; Svensson, Elin; Tadolini, M.; Thomas, T. A.; Tiberi, S.; Trubiano, J.; Udwadia, Z. F.; Verhage, A. R.; Vu, D. H.; Akkerman, O. W.; Alffenaar, J. W. C.; Denholm, J. T.
Clinical standards for the management of adverse effects during treatment for TB
2023
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Garcia-Prats, Anthony J.; Hoddinott, Graeme; Howell, Pauline; Hughes, Jennifer; Jean-Philippe, Patrick; Kim, Soyeon; Palmer, Megan; Schaaf, H. Simon; Seddon, James A.; Svensson, Elin; Hesseling, Anneke C.
Children deserve simple, short, safe, and effective treatment for rifampicin-resistant tuberculosis
2023
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Dierig, A.; Hoelscher, M.; Schultz, S.; Hoffmann, L.; Jarchow-MacDonald, A.; Svensson, Elin; Te Brake, L.; Aarnoutse, R.; Boeree, M.; McHugh, T. D.; Wildner, L. M.; Gong, X.; Phillips, P. P. J.; Minja, L. T.; Ntinginya, N.; Mpagama, S.; Liyoyo, A.; Wallis, R. S.; Sebe, M.; Mhimbira, F. A.; Mbeya, B.; Rassool, M.; Geiter, L.; Cho, Y. L.; Heinrich, N.
A phase IIb, open-label, randomized controlled dose ranging multi-centre trial to evaluate the safety, tolerability, pharmacokinetics and exposure-response relationship of different doses of delpazolid in combination with bedaquiline delamanid moxifloxacin in adult subjects with newly diagnosed, uncomplicated, smear-positive, drug-sensitive pulmonary tuberculosis
2023
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Bukkems, Laura; Jönsson, Siv; Cnossen, Marjon O.; Karlsson, Mats; Mathot, Ron A. A.
Relationship between factor VIII levels and bleeding for rFVIII-SingleChain in severe hemophilia A: A repeated time-to-event analysis
2023
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Susanto, Budi O.; Svensson, Elin M.; te Brake, Lindsey; Aarnoutse, Rob E.; Boeree, Martin J.; Simonsson, Ulrika S. H.
Model-based analysis of bactericidal activity and a new dosing strategy for optimised-dose rifampicin
2023
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Koele, Simon E.; Phillips, Patrick P. J.; Upton, Caryn M.; van Ingen, Jakko; Simonsson, Ulrika S. H.; Diacon, Andreas H.; Aarnoutse, Rob E.; Svensson, Elin M.
Early bactericidal activity studies for pulmonary tuberculosis: A systematic review of methodological aspects
2023
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Diaz, Jessica M. Aguilar; Abulfathi, Ahmed A.; te Brake, Lindsey H. M.; van Ingen, Jakko; Kuipers, Saskia; Magis-Escurra, Cecile; Raaijmakers, Jelmer; Svensson, Elin; Boeree, Martin J.
New and Repurposed Drugs for the Treatment of Active Tuberculosis: An Update for Clinicians
2023
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Litjens, Carlijn H. C.; Verscheijden, Laurens F. M.; Svensson, Elin M.; van den Broek, Petra H. H.; van Hove, Hedwig; Koenderink, Jan B.; Russel, Frans G. M.; Aarnoutse, Rob E.; te Brake, Lindsey H. M.
Physiologically-Based Pharmacokinetic Modelling to Predict the Pharmacokinetics and Pharmacodynamics of Linezolid in Adults and Children with Tuberculous Meningitis
2023
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Albitar, Orwa; Ghadzi, Siti Maisharah Sheikh; Harun, Sabariah Noor; Ahmad, Siti Nor Aizah; Kjellsson, Maria C.
Pharmacometric modeling of drug adverse effects: an application of mixture models in schizophrenia spectrum disorder patients treated with clozapine
2023
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Centanni, Maddalena; Thijs, Abel; Desar, Ingrid; Karlsson, Mats O.; Friberg, Lena E.
Optimization of blood pressure measurement practices for pharmacodynamic analyses of tyrosine-kinase inhibitors
2023
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Madathil Krishnan, Sreenath; Friberg, Lena; Mercier, Francois; Zhang, Rong; Wu, Ben; Jin, Jin Y.; Hoang, Tien; Ballinger, Marcus; Bruno, Rene; Karlsson, Mats
Multistate Pharmacometric Model to Define the Impact of Second-Line Immunotherapies on the Survival Outcome of the IMpower131 Study
2023
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Chasseloup, Estelle; Karlsson, Mats
Comparison of Seven Non-Linear Mixed Effect Model-Based Approaches to Test for Treatment Effect
2023
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Swen, JesseJ; van der Wouden, Cathelijne H.; Manson, Lisanne E. N.; Abdullah-Koolmees, Heshu; Blagec, Kathrin; Blagus, Tanja; Böhringer, Stefan; Cambon-Thomsen, Anne; Cecchin, Erika; Cheung, Ka-Chun; Deneer, Vera H. M.; Dupui, Mathilde; Ingelman-Sundberg, Magnus; Jönsson, Siv; Joefield-Roka, Candace; Just, Katja S.; Karlsson, Mats; Konta, Lidija; Koopmann, Rudolf; Kriek, Marjolein; Lehr, Thorsten; Mitropoulou, Christina; Rial-Sebbag, Emmanuelle; Rollinson, Victoria; Roncato, Rossana; Samwald, Matthias; Schaeffeler, Elke; Skokou, Maria; Schwab, Matthias; Steinberger, Daniela; Stingl, Julia C.; Tremmel, Roman; Turner, Richard M.; van Rhenen, Mandy H.; Fajardo, Cristina L. Davila; Dolzan, Vita; Patrinos, George P.; Pirmohamed, Munir; Sunder-Plassmann, Gere; Toffoli, Giuseppe; Guchelaar, Henk-Jan
A 12-gene pharmacogenetic panel to prevent adverse drug reactions: an open-label, multicentre, controlled, cluster-randomised crossover implementation study
2023
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Kempen, Thomas; Hedman, Anton N.; Hadziosmanovic, Nermin; Lindner, Karl‐Johan; Melhus, Håkan; Nielsen, Elisabet I.; Sulku, Johanna; Gillespie, Ulrika
Risk factors for and preventability of drug‐related hospital revisits in older patients: A post‐hoc analysis of a randomized clinical trial
2023
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Ayoun Alsoud, Rami; Svensson, Robin J.; Svensson, Elin; Gillespie, Stephen H. H.; Boeree, Martin J. J.; Diacon, Andreas H. H.; Dawson, Rodney; Aarnoutse, Rob E. E.; Simonsson, Ulrika S. H.
Combined quantitative tuberculosis biomarker model for time-to-positivity and colony forming unit to support tuberculosis drug development
2023
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Siebinga, Hinke; de Wit-van der Veen, Berlinda J. J.; Beijnen, Jos H.; Dorlo, Thomas P. C.; Huitema, Alwin D. R.; Hendrikx, Jeroen J. M. A.
A physiologically based pharmacokinetic model for [Ga-68]Ga-(HA-)DOTATATE to predict whole-body distribution and tumor sink effects in GEP-NET patients
2023
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Prins, H. A. B.; Zino, L.; Svensson, Elin M.; Verbon, A.; de Bree, G. J.; Prins, J. M.; Reiss, P.; Burger, D. M.; Rokx, C.; Colbers, A.; Team, NOVA Study
Exposure and virologic outcomes of dolutegravir combined with ritonavir boosted darunavir in treatment-naive individuals enrolled in the Netherlands Cohort Study on Acute HIV infection (NOVA)
2023
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Chu, Wan-Yu; Annink, Kim V; Nijstad, A Laura; Maiwald, Christian A; Schroth, Michael; Bakkali, Loubna El; van Bel, Frank; Benders, Manon J N L; van Weissenbruch, Mirjam M; Hagen, Anja; Franz, Axel R; Dorlo, Thomas P. C.; Allegaert, Karel; Huitema, Alwin D R
Pharmacokinetic/Pharmacodynamic Modelling of Allopurinol, its Active Metabolite Oxypurinol, and Biomarkers Hypoxanthine, Xanthine and Uric Acid in Hypoxic-Ischemic Encephalopathy Neonates
2022
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Damoiseaux, David; Calpe, Silvia; Rosing, Hilde; Beijnen, Jos H; Huitema, Alwin D R; Lok, Christianne; Dorlo, Thomas P. C.; Amant, Frédéric
Presence of Five Chemotherapeutic Drugs in Breast Milk as a Guide for the Safe Use of Chemotherapy During Breastfeeding: Results From a Case Series.
2022
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Damoiseaux, David; Li, Wenlong; Beijnen, Jos H; Schinkel, Alfred H; Huitema, Alwin D R; Dorlo, Thomas P. C.
Population Pharmacokinetic Modelling to Support the Evaluation of Preclinical Pharmacokinetic Experiments with Lorlatinib
2022
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Janssen, Julie M; Verheijen, Remy B; van Duijl, Tirsa T; Lin, Lishi; van den Heuvel, Michel M; Beijnen, Jos H; Steeghs, Neeltje; van den Broek, Daan; Huitema, Alwin D R; Dorlo, Thomas P. C.
Longitudinal nonlinear mixed effects modeling of EGFR mutations in ctDNA as predictor of disease progression in treatment of EGFR-mutant non-small cell lung cancer.
2022
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Tanneau, Lénaïg; Karlsson, Mats; Rosenkranz, Susan L.; Cramer, Yoninah S.; Shenje, Justin; Upton, Caryn M.; Morganroth, Joel; Diacon, Andreas H.; Maartens, Gary; Dooley, Kelly E.; Svensson, Elin
Assessing Prolongation of the Corrected QT Interval with Bedaquiline and Delamanid Coadministration to Predict the Cardiac Safety of Simplified Dosing Regimens
2022
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Molenaar-Kuijsten, Laura; Verheijen, Remy B; Jacobs, Bart A W; Thijssen, Bas; Rosing, Hilde; Dorlo, Thomas P. C.; Beijnen, Jos H; Steeghs, Neeltje; Huitema, Alwin D R
Everolimus Concentration in Saliva to Predict Stomatitis: A Feasibility Study in Patients with Cancer.
2022
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Roseboom, Ignace C; Thijssen, Bas; Rosing, Hilde; Alves, Fabiana; Sundar, Shyam; Beijnen, Jos H; Dorlo, Thomas P. C.
Development and validation of a high-performance liquid chromatography tandem mass spectrometry method for the quantification of the antiparasitic and antifungal drug amphotericin B in human skin tissue.
2022
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Roseboom, Ignace C; Thijssen, Bas; Rosing, Hilde; Alves, Fabiana; Mondal, Dinesh; Teunissen, Marcel B M; Beijnen, Jos H; Dorlo, Thomas P. C.
Development and validation of an HPLC-MS/MS method for the quantification of the anti-leishmanial drug miltefosine in human skin tissue.
2022
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Roseboom, Ignace C; Thijssen, Bas; Rosing, Hilde; Alves, Fabiana; Younis, Brima M; Musa, Ahmed M; Beijnen, Jos H; Dorlo, Thomas P. C.
Development and validation of an ultra-high performance liquid chromatography coupled to tandem mass spectrometry method for the quantification of the antileishmanial drug paromomycin in human skin tissue.
2022
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van Eijk, Maarten; Yu, Huixin; Sawicki, Emilia; de Weger, Vincent A; Nuijen, Bastiaan; Dorlo, Thomas P. C.; Beijnen, Jos H; Huitema, Alwin D R
Development of a population pharmacokinetic/pharmacodynamic model for various oral paclitaxel formulations co-administered with ritonavir and thrombospondin-1 based on data from early phase clinical studies.
2022
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Simeoli, Raffaele; Dorlo, Thomas P. C.; Hanff, Lidwien M; Huitema, Alwin D R; Dreesen, Erwin
Editorial: Therapeutic Drug Monitoring (TDM)
2022
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Palić, Semra; Beijnen, Jos H; Dorlo, Thomas P. C.
An update on the clinical pharmacology of miltefosine in the treatment of leishmaniasis.
2022
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Kempen, Thomas Gerardus Hendrik; Hedman, Anton; Gillespie, Ulrika
Drug-related emergency department visits in older patients: an applicability and reliability study of an existing assessment tool
2022
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Wilkins, Justin J.; Svensson, Elin; Ernest, Jacqueline P.; Savic, Radojka M.; Simonsson, Ulrika S. H.; McIlleron, Helen
Pharmacometrics in tuberculosis: progress and opportunities
2022
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Abulfathi, Ahmed A.; Chaba, Linda A.; Svensson, Elin; Pillai, Goonaseelan C.; Rosenkranz, Bernd
Pharmacometrics - tools to assure optimal medicine use in low- and middle-income countries: Editorial
2022
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Denti, Paolo; Wasmann, Roeland E.; van Rie, Annelies; Winckler, Jana; Bekker, Adrie; Rabie, Helena; Hesseling, Anneke C.; van der Laan, Louvina E.; Gonzalez-Martinez, Carmen; Zar, Heather J.; Davies, Gerry; Wiesner, Lubbe; Svensson, Elin; McIlleron, Helen M.
Optimizing Dosing and Fixed-Dose Combinations of Rifampicin, Isoniazid, and Pyrazinamide in Pediatric Patients With Tuberculosis: A Prospective Population Pharmacokinetic Study
2022
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Dreesen, Erwin; Gijsen, Matthias; Elkayal, Omar; Annaert, Pieter; Debaveye, Yves; Wauters, Joost; Karlsson, Mats O.; Spriet, Isabel
Ceftriaxone dosing based on the predicted probability of augmented renal clearance in critically ill patients with pneumonia
2022
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Bulman, Zackery P.; Wicha, Sebastian G.; Nielsen, Elisabet I.; Lenhard, Justin R.; Nation, Roger L.; Theuretzbacher, Ursula; Derendorf, Hartmut; Tängdén, Thomas; Zeitlinger, Markus; Landersdorfer, Cornelia B.; Bulitta, Jürgen B.; Friberg, Lena; Li, Jian; Tsuji, Brian T.
Research priorities towards precision antibiotic therapy to improve patient care
2022
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Musa, Ahmed M; Mbui, Jane; Mohammed, Rezika; Olobo, Joseph; Ritmeijer, Koert; Alcoba, Gabriel; Muthoni Ouattara, Gina; Egondi, Thaddaeus; Nakanwagi, Prossy; Omollo, Truphosa; Wasunna, Monique; Verrest, Luka; Dorlo, Thomas P. C.; Musa Younis, Brima; Nour, Ali; Taha Ahmed Elmukashfi, Elmukashfi; Ismail Omer Haroun, Ahmed; Khalil, Eltahir A G; Njenga, Simon; Fikre, Helina; Mekonnen, Tigist; Mersha, Dagnew; Sisay, Kasaye; Sagaki, Patrick; Alvar, Jorge; Solomos, Alexandra; Alves, Fabiana
Paromomycin and Miltefosine Combination as an Alternative to Treat Patients With Visceral Leishmaniasis in Eastern Africa: A Randomized, Controlled, Multicountry Trial.
2022
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van der Heijden, Lisa; van Nuland, Merel; Beijnen, Jos; Huitema, Alwin; Dorlo, Thomas P. C.
A naïve pooled data approach for extrapolation of Phase 0 microdose trials to therapeutic dosing regimens.
2022
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Roseboom, Ignace C; Rosing, Hilde; Beijnen, Jos H; Dorlo, Thomas P. C.
Bioanalytical methods for pharmacokinetic studies of antileishmanial drugs.
2022
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Hinds, Terry D.; Valoti, Massimo; Lai, Yurong; Dorlo, Thomas P. C.; Li, Yan
Emerging talents in Frontiers in Pharmacology: Drug metabolism and transport 2022
2022