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Is the recommended dose of efavirenz optimal in young West African human immunodeficiency virus-infected children?

, : Is the recommended dose of efavirenz optimal in young West African human immunodeficiency virus-infected children?. Antimicrobial Agents and ChemoTherapy 53(10): 4407-4413

We aimed in this study to describe efavirenz concentration-time courses in treatment-naïve children after once-daily administration to study the effects of age and body weight on efavirenz pharmacokinetics and to test relationships between doses, plasma concentrations, and efficacy. For this purpose, efavirenz concentrations in 48 children were measured after 2 weeks of didanosine-lamivudine-efavirenz treatment, and samples were available for 9/48 children between months 2 and 5 of treatment. Efavirenz concentrations in 200 plasma specimens were measured using a validated high-performance liquid chromatography method. A population pharmacokinetic model was developed with NONMEM. The influence of individual characteristics was tested using a likelihood ratio test. The estimated minimal and maximal concentrations of efavirenz in plasma (Cmin and Cmax, respectively) and the area under the concentration-time curve (AUC) were correlated to the decrease in human immunodeficiency virus type 1 RNA levels after 3 months of treatment. The threshold Cmin (and AUC) that improved efficacy was determined. The target minimal concentration of 4 mg/liter was considered for toxicity. An optimized dosing schedule that would place the highest percentage of children in the interval of effective and nontoxic concentrations was simulated. The pharmacokinetics of efavirenz was best described by a one-compartment model with first-order absorption and elimination. The mean apparent clearance and volume of distribution for efavirenz were 0.211 liter/h/kg and 4.48 liters/kg, respectively. Clearance decreased significantly with age. When the recommended doses were given to 46 of the 48 children, 19% (44% of children weighing less than 15 kg) had C(min)s below 1 mg/liter. A significantly higher percentage of children with C(min)s of >1.1 mg/liter or AUCs of >51 mg/liter x h than of children with lower values had viral load decreases greater than 2 log10 copies/ml after 3 months of treatment. Therefore, to optimize the percentage of children with C(min)s between 1.1 and 4 mg/liter, children should receive the following once-daily efavirenz doses: 25 mg/kg of body weight from 2 to 6 years, 15 mg/kg from 6 to 10 years, and 10 mg/kg from 10 to 15 years. These assumptions should be prospectively confirmed.


PMID: 19635964

DOI: 10.1128/AAC.01594-08

Other references

Lee, W.; Gillies, J.P.; Jose, D.; Israels, B.A.; von Hippel, P.H.; Marcus, A.H., 2016: Single-molecule FRET studies of the cooperative and non-cooperative binding kinetics of the bacteriophage T4 single-stranded DNA binding protein (gp32) to ssDNA lattices at replication fork junctions. NlmCategory="UNASSIGNED">Gene 32 protein (gp32) is the single-stranded (ss) DNA binding protein of the bacteriophage T4. It binds transiently and cooperatively to ssDNA sequences exposed during the DNA replication process and regulate...

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Bohrmann, H.; Schneider, G.; Kern, H., 1975: Sweet sliceable sandwich spread and process for its manufacture. A product with a high protein content which is sold in slices in a transparent packaging for making sandwiches consists of glycerides of natural fatty acids, sodium caseinate, tri-sodium-hydrogen-diphosphate, emulsifying agents, sweeteners and wat...

L.R.chelle P.; Roy M.; Tavenas F., 1973: Field measurements of cohesion in Champlain clays. Proceedings of the International Conference on Soil Mechanics and Foundation Engineering = Comptes Rendus du Congres International de Mecanique des Sols et des Travaux de Fondations: l. 1, Part 1-2, Methods of investigating strength and deformability of soils, Pages 229-236. 1973.

Trulsson, U.; Strandmark, M.; Mohlin, B.; Berggren, U., 2002: A qualitative study of teenagers' decisions to undergo orthodontic treatment with fixed appliance. The aim of this study was to describe thoughts and values influencing young people's choices to undergo orthodontic treatment. Twenty-eight patients (11 boys), aged 13-19 years, at an orthodontic clinic in the western part of Sweden participa...

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