Portfolio

Professional portfolio showcasing pharmacometric modeling projects, software development, and scientific research in clinical pharmacology and drug development.

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Software

VSCode/VSX extension for NMTRAN (NONMEM)

https://github.com/vrognas/vscode-nmtran

An extension written in TypeScript, adding support for the NMTRAN language used in NONMEM control streams.

Available on the VSCode marketplace and Open VSX.

Programmatic Language Features

Diagnostics
Code completion proposals
Hover info

Declarative Language Features

Comment toggling using the VS Code command Toggle Line Comment
Folding (by control records)
Bracket matching
Bracket autoclosing
Bracket autosurrounding

Syntax Highlighting

By tokenization according to TextMate 1.5.1 naming conventions

Snippet Completion

Selection of available snippets

Subroutine selection
- ADVAN and TRANS
Modify $DATA on-the-fly (Credit: Simon Buatois)
RUV (normal or log-scale)
- RUV_add
- RUV_prop
- RUV_addprop
Creating an Xpose-friendly $TABLE scaffold (just type $TABLE).
MIXTURE-models (just type $MIX)
- 2-way mixture model
- 3-way mixture model
Including IIV on a parameter that is bound between 0 and 1 (type logit_iiv).
Baseline modeling (B1, B2, B3, B4) Dansirikul et al., 2008
BQL modeling (M3) Beal, 2001

NMTRAN syntax highlighting in VS Code showing control stream records with color-coded keywords, variables, and comments for better code readability

Animated demonstration of ADVAN snippet completion in VS Code, showing autocomplete suggestions for NONMEM subroutine selection with ADVAN and TRANS options

Science

Population pharmacokinetics of colistin and the relation to survival in critically ill patients infected with colistin susceptible and carbapenem-resistant bacteria

Kristoffersson AN^*, Rognås V^*, Brill MJE^*, et al. (^*shared first authorship)

Clin Microbiol Infect (2020)

https://doi.org/10.1016/j.cmi.2020.03.016

Objectives

The aim was to analyse the population pharmacokinetics of colistin and to explore the relationship between colistin exposure and time to death.

Methods

Patients included in the AIDA randomized controlled trial were treated with colistin for severe infections caused by carbapenem-resistant Gram-negative bacteria. All subjects received a 9 million units (MU) loading dose, followed by a 4.5 MU twice daily maintenance dose, with dose reduction if creatinine clearance (CrCL) <50 mL/min. Individual colistin exposures were estimated from the developed population pharmacokinetic model and an optimized two-sample per patient sampling design. Time to death was evaluated in a parametric survival analysis.

Results

Out of 406 randomized patients, 349 contributed pharmacokinetic data. The median (90% range) colistin plasma concentration was 0.44 (0.14–1.59) mg/L at 15 minutes after the end of first infusion. In samples drawn 10 h after a maintenance dose, concentrations were >2 mg/L in 94% (195/208) and 44% (38/87) of patients with CrCL ≤120 mL/min, and > 120 ml/min, respectively. Colistin methanesulfonate sodium (CMS) and colistin clearances were strongly dependent on CrCL. High colistin exposure to MIC ratio was associated with increased hazard of death in the multivariate analysis (adjusted hazard ratio (95% CI): 1.07 (1.03–1.12)). Other significant predictors included SOFA score at baseline (HR 1.24 (1.19–1.30) per score increase), age and Acinetobacter or Pseudomonas as index pathogen.

Discussion

The population pharmacokinetic model predicted that >90% of the patients had colistin concentrations >2 mg/L at steady state, but only 66% at 4 h after start of treatment. High colistin exposure was associated with poor kidney function, and was not related to a prolonged survival.

Turn-over model characterizing effect of colistin on serum-creatinine in critically ill patients

Rognås V et al.

https://www.page-meeting.org/default.asp?abstract=9869

Scientific poster showing turn-over model characterizing effect of colistin on serum creatinine in critically ill patients with mathematical equations and population pharmacokinetic modeling results

Bounded integer approach to model time-varying SOFA scores from patients with carbapenem resistant infections

Rognås V et al.

https://www.page-meeting.org/default.asp?abstract=9052

Scientific poster displaying bounded integer approach for modeling time-varying SOFA scores in patients with carbapenem-resistant infections, showing statistical methodology and clinical outcomes data

A semi-mechanistic population pharmacokinetic-pharmacodynamic model to assess downstream drug-target effects on erythropoiesis

Rognås SV et al.

J Pharmacokinet Pharmacodyn (2025)

https://doi.org/10.1007/s10928-025-09990-7

Erythropoiesis is a complex process that results in the production of erythrocytes from hematopoietic stem cells in the bone marrow. This work aimed to develop a population pharmacokinetic-pharmacodynamic (PKPD) model describing erythropoiesis and hemoglobin synthesis following bitopertin, an inhibitor of glycine transporter 1 (GlyT1), administration. Data from a Phase 1 clinical trial in 67 healthy subjects administered bitopertin (10, 30, or 60 mg) or placebo for 120 days were analyzed. Hematological assessments included erythrocyte and reticulocyte counts, immature reticulocyte fraction, hemoglobin concentration, and mean corpuscular hemoglobin. The proposed semi-mechanistic model, which leverages data and physiological knowledge, was found to adequately simultaneously describe the dose- and time-dependent changes in the biomarkers. The framework was used to illustrate the potential outcome of hypothetical drug-target interactions at distinct stages of erythropoiesis and hemoglobin synthesis, exemplifying its usefulness in a clinical setting.