FRINK Linked Data Fragments server

Matches in SemOpenAlex for { <https://semopenalex.org/work/W1567127141> ?p ?o ?g. }

• W1567127141 abstract "In the face of growing drug resistance, the World Health Organization (WHO) has issued recommendations strongly encouraging the use of combination therapies to combat uncomplicated malaria. Amongst the most effective treatments are those combining an artemisinin derivative with a longer acting component such as amodiaquine, lumefantrine or piperaquine. Despite the widespread use of these treatments there is a lack of understanding regarding both pharmacokinetics and pharmacodynamics of the combinations, particularly in pediatric patients. The aim of this thesis was to describe how the dosing of antimalarials during combination therapy correlates with the outcome of treatment and to investigate factors that may influence this relationship. In order to evaluate the pharmacokinetics and pharmacodynamics of the combinations artesunate + amodiaquine and artemether + lumefantrine in pediatric patients, a group particularly vulnerable to malaria, studies were conducted during the implementation of these new treatment strategies in Tanzania. The population approach to analysing the pharmacokinetics and pharmacodynamics was used in these studies. This method allows the determination of the typical values of pharmacokinetic and pharmacodynamic parameters, as well as the description of the variability in these estimates in the population, from sparse data. Importantly, the method also allows the investigation of how covariates, such as demographics (weight, age) or food intake influences pharmacokinetics and/or pharmacodynamics. An in vitro study was conducted to characterize the plasma protein binding of amodiaquine and its primary metabolite N-desethylamodiaquine. The influence of concomitant intake of a typical Vietnamese meal on the absorption of piperaquine was investigated in healthy subjects. There was a significant, albeit weak, correlation between the clinical outcome of the combination amodiaquine+artesunate and exposure to N-desethylamodiaquine. Amodiaquine and N-desethylamodiaquine were both shown to be extensively bound to plasma proteins in vitro, which may explain the difficulty in establishing a good concentration-effect relationship from total N-desethylamodiaquine concentrations. The proposed semi-mechanistic model of parasite dynamics adequately described the effect of artemether and its active metabolite DHA on the parasite density in malaria patients, with predicted median parasite clearance time corresponding well with the observed. To make full use of the model, however, stage-specific parasite counts should be obtained both prior to, and during, drug treatment. There was no significant impact on the exposure to piperaquine due to concomitant intake of a relatively low-fat meal. The 20-fold range in exposure in both fed and fasting subjects suggests that there are other factors contributing significantly to interindividual differences in piperaquine pharmacokinetics." @default.
• W1567127141 created "2016-06-24" @default.
• W1567127141 creator A5030330578 @default.
• W1567127141 date "2009-04-23" @default.
• W1567127141 modified "2023-09-26" @default.
• W1567127141 title "Clinical pharmacokinetics and pharmacodynamics of antimalarial combination therapy" @default.
• W1567127141 cites W1483203554 @default.
• W1567127141 cites W1525415484 @default.
• W1567127141 cites W1525774039 @default.
• W1567127141 cites W1527428657 @default.
• W1567127141 cites W1548735594 @default.
• W1567127141 cites W1550518551 @default.
• W1567127141 cites W1587707825 @default.
• W1567127141 cites W1588073060 @default.
• W1567127141 cites W1660290614 @default.
• W1567127141 cites W1795494388 @default.
• W1567127141 cites W1921967810 @default.
• W1567127141 cites W1945827446 @default.
• W1567127141 cites W1964860455 @default.
• W1567127141 cites W1965250537 @default.
• W1567127141 cites W1965987183 @default.
• W1567127141 cites W1966411384 @default.
• W1567127141 cites W1967723196 @default.
• W1567127141 cites W1968866616 @default.
• W1567127141 cites W1970856471 @default.
• W1567127141 cites W1982885575 @default.
• W1567127141 cites W1986075689 @default.
• W1567127141 cites W1988678216 @default.
• W1567127141 cites W1991072114 @default.
• W1567127141 cites W1998973191 @default.
• W1567127141 cites W1999531606 @default.
• W1567127141 cites W2005087339 @default.
• W1567127141 cites W2005769414 @default.
• W1567127141 cites W2008658167 @default.
• W1567127141 cites W2009038519 @default.
• W1567127141 cites W2010154952 @default.
• W1567127141 cites W2021371898 @default.
• W1567127141 cites W2027860481 @default.
• W1567127141 cites W2027962704 @default.
• W1567127141 cites W203031526 @default.
• W1567127141 cites W2033721665 @default.
• W1567127141 cites W2035183545 @default.
• W1567127141 cites W2039060251 @default.
• W1567127141 cites W2039639971 @default.
• W1567127141 cites W2040713555 @default.
• W1567127141 cites W2040751392 @default.
• W1567127141 cites W2045567622 @default.
• W1567127141 cites W2046415190 @default.
• W1567127141 cites W2046969631 @default.
• W1567127141 cites W2049557047 @default.
• W1567127141 cites W2049932853 @default.
• W1567127141 cites W2055517049 @default.
• W1567127141 cites W2057641375 @default.
• W1567127141 cites W2059149303 @default.
• W1567127141 cites W2059636803 @default.
• W1567127141 cites W2062432044 @default.
• W1567127141 cites W2063725332 @default.
• W1567127141 cites W2066464642 @default.
• W1567127141 cites W2070458547 @default.
• W1567127141 cites W2078108823 @default.
• W1567127141 cites W2079395738 @default.
• W1567127141 cites W2079901176 @default.
• W1567127141 cites W2083184969 @default.
• W1567127141 cites W2084147970 @default.
• W1567127141 cites W2088379477 @default.
• W1567127141 cites W2090726723 @default.
• W1567127141 cites W2092661856 @default.
• W1567127141 cites W2093949878 @default.
• W1567127141 cites W2098184601 @default.
• W1567127141 cites W2103049577 @default.
• W1567127141 cites W2105136979 @default.
• W1567127141 cites W2107958611 @default.
• W1567127141 cites W2108972405 @default.
• W1567127141 cites W2111813303 @default.
• W1567127141 cites W2114903378 @default.
• W1567127141 cites W2116219018 @default.
• W1567127141 cites W2116913457 @default.
• W1567127141 cites W2120605254 @default.
• W1567127141 cites W2123960222 @default.
• W1567127141 cites W2126755683 @default.
• W1567127141 cites W2128371334 @default.
• W1567127141 cites W2129421857 @default.
• W1567127141 cites W2129723380 @default.
• W1567127141 cites W2139729859 @default.
• W1567127141 cites W2139957409 @default.
• W1567127141 cites W2146859121 @default.
• W1567127141 cites W2152669826 @default.
• W1567127141 cites W2156295588 @default.
• W1567127141 cites W2159056342 @default.
• W1567127141 cites W2162729310 @default.
• W1567127141 cites W2166363384 @default.
• W1567127141 cites W2166602226 @default.
• W1567127141 cites W2168202960 @default.
• W1567127141 cites W2208255752 @default.
• W1567127141 cites W2230049830 @default.
• W1567127141 cites W2301023468 @default.
• W1567127141 cites W2402608199 @default.
• W1567127141 cites W2403514952 @default.
• W1567127141 cites W2424782909 @default.
• W1567127141 cites W2437899067 @default.

• next