* Modelling the time course of antimalarial parasite killing: a tour of animal and human models, translation and challenges.
- Malaria remains a global public health concern and current treatment options are suboptimal in some clinical settings. For effective chemotherapy, antimalarial drug concentrations must be sufficient to remove completely all of the parasites in the infected host. Optimized dosing therefore requires a detailed understanding of the time course of antimalarial response, whilst simultaneously considering the parasite life cycle and host immune elimination. Recently, the World Health Organization (WHO) has recommended the development of mathematical models for understanding better antimalarial drug resistance and management. Other international groups have also suggested that mechanistic pharmacokinetic (PK) and pharmacodynamic (PD) models can support the rationalization of antimalarial dosing strategies. At present, artemisinin-based combination therapy (ACT) is recommended as first line treatment of falciparum malaria for all patient groups. This review summarizes the PK-PD characterization of artemisinin derivatives and other partner drugs from both preclinical studies and human clinical trials. We outline the continuous and discrete time models that have been proposed to describe antimalarial activity on specific stages of the parasite life cycle. The translation of PK-PD predictions from animals to humans is considered, because preclinical studies can provide rich data for detailed mechanism-based modelling. While similar sampling techniques are limited in clinical studies, PK-PD models can be used to optimize the design of experiments to improve estimation of the parameters of interest. Ultimately, we propose that fully developed mechanistic models can simulate and rationalize ACT or other treatment strategies in antimalarial chemotherapy.
=>初めて, 最初の, 第一の, はじめに, 最初, 第1
Overview of noun first
The noun first has 6 senses (first 4 from tagged texts)
1. (9) first, number one -- (the first or highest in an ordering or series; "He wanted to be the
first")
2. (5) first, number one, number 1 -- (the first element in a countable series; "the first of the
month")
3. (1) beginning, commencement, first, outset, get-go, start, kickoff, starting time, showtime,
offset -- (the time at which something is supposed to begin; "they got an early start"; "she knew
from the get-go that he was the man for her")
4. (1) first base, first -- (the fielding position of the player on a baseball team who is stationed
at first of the bases in the infield (counting counterclockwise from home plate))
5. first, first-class honours degree -- (an honours degree of the highest class)
6. first gear, first, low gear, low -- (the lowest forward gear ratio in the gear box of a motor
vehicle; used to start a car moving)
Overview of adj first
The adj first has 6 senses (first 5 from tagged texts)
1. (232) first -- (preceding all others in time or space or degree; "the first house on the right";
"the first day of spring"; "his first political race"; "her first baby"; "the first time"; "the
first meetings of the new party"; "the first phase of his training")
2. (61) first, 1st -- (indicating the beginning unit in a series)
3. (4) inaugural, initiative, initiatory, first, maiden -- (serving to set in motion; "the
magazine's inaugural issue"; "the initiative phase in the negotiations"; "an initiatory step toward
a treaty"; "his first (or maiden) speech in Congress"; "the liner's maiden voyage")
4. (4) beginning, first -- (serving to begin; "the beginning canto of the poem"; "the first verse")
5. (3) first, foremost, world-class -- (ranking above all others; "was first in her class"; "the
foremost figure among marine artists"; "the top graduate")
6. first -- (highest in pitch or chief among parts or voices or instruments or orchestra sections;
"first soprano"; "the first violin section"; "played first horn")
Overview of adv first
The adv first has 4 senses (first 4 from tagged texts)
1. (58) first, firstly, foremost, first of all, first off -- (before anything else; "first we must
consider the garter snake")
2. (40) first, for the first time -- (the initial time; "when Felix first saw a garter snake")
3. (9) first -- (before another in time, space, or importance; "I was here first"; "let's do this
job first")
4. (4) foremost, first -- (prominently forward; "he put his best foot foremost")
--- WordNet end ---