ProjektportalTranslational pharmacometrics for the parasitic disease cutaneous leishmaniasis
Terrmin
HT25
Beskrivning
Cutaneous Leishmaniasis (CL) is the most common disease manifestation of the neglected tropical disease leishmaniasis, caused by various species of the protozoan parasite genus Leishmania. Despite potentially causing lifelong scarring, serious disability, and social stigmatization, current treatment options have severe limitations in terms of safety, efficacy, and cost. Consequently, there is an urgent need for new, safe, and effective drug therapies to combat CL.
The Drugs for Neglected Diseases Initiative (DNDi) has identified the nitroimidazole DNDI-0690 as a drug candidate, demonstrating excellent anti-leishmanial activity in various in vitro and in vivo CL models. The overall aim of this project is to develop a pharmacokinetic-pharmacodynamic (PK/PD) model for the preclinical-to-clinical translation of the oral drug DNDI-0690 for CL. Specifically, an established nonlinear mixed-effects modeling framework will be used to quantify the relationship between plasma/skin exposure and repeated individual longitudinal parasite loads over time, as measured by bioluminescence imaging in a mouse model infected with luciferase expressing Leishmania major parasites. Additionally, the relationship between parasite clearance and lesion size reduction will be characterized.
The murine exposure-response relationship will be integrated with scaled human PK, and dosing scenarios in humans will be simulated to determine an effective clinical dose of DNDI-0690.
The project involves data-driven, computer-based pharmacometric modeling and simulation techniques, primarily conducted in the statistical software R and the nonlinear mixed-effects modeling software NONMEM. Experience in R is considered necessary, while experience in NONMEM is not required but considered a merit.
The work will be carried out in Uppsala in a research group that offers an international environment. The working language, including supervision, will be English.
Does this project sounds like something for you? Apply here or contact the supervisor (see below) or Maria Kjellsson (maria.kjellsson@uu.se) if you have additional questions. We look forward to your application!
Huvudområde
Farmaceutisk vetenskap
Ämne
Farmakometri
Typ
Beräkningsstudie
Företag
Uppsala University
Ort/Plats
Uppsala
Handledarens namn
Rasmus Henninger, Thomas Dorlo
Handledarens e-post
rasmus.henninger@uu.se, thomas.dorlo@uu.se
Institution
Institutionen för farmaci
Program
Masterprogram i läkemedelsmodellering
Kurs
Degree Project in Pharmaceutical Modeling within Pharmacometrics 45 c - 3FB029
Omfattning/hp
45hp
Hur många studenter kan antagas för detta projekt?
1