Dataset Information

Dose evaluation of lamivudine in human immunodeficiency virus-infected children aged 5 months to 18 years based on a population pharmacokinetic analysis.

ABSTRACT:

Aim

The objectives of this study were to characterize age-related changes in lamivudine pharmacokinetics in children and evaluate lamivudine exposure, followed by dose recommendations for subgroups in which target steady state area under the daily plasma concentration-time curve (AUC_0-24h ) is not reached.

Methods

Population pharmacokinetic modelling was performed in NONMEM using data from two model-building datasets and two external datasets [n = 180 (age 0.4-18 years, body weight 3.4-60.5 kg); 2061 samples (median 12 per child); daily oral dose 60-300 mg (3.9-17.6 mg kg^-1 )]. Steady state AUC_0-24h was calculated per individual (adult target 8.9 mg·h l^-1 ).

Results

A two-compartment model with sequential zero order and first order absorption best described the data. Apparent clearance and central volume of distribution (% RSE) were 13.2 l h^-1 (4.2%) and 38.9 l (7.0%) for a median individual of 16.6 kg, respectively. Bodyweight was identified as covariate on apparent clearance and volume of distribution using power functions (exponents 0.506 (20.2%) and 0.489 (32.3%), respectively). The external evaluation supported the predictive ability of the final model. In 94.5% and 35.8% of the children with a body weight >14 kg and <14 kg, respectively, the target AUC_0-24h was reached.

Conclusion

Bodyweight best predicted the developmental changes in apparent lamivudine clearance and volume of distribution. For children aged 5 months-18 years with a body weight <14 kg, the dose should be increased from 8 to 10 mg kg^-1 day^-1 if the adult target for AUC_0-24h is aimed for. In order to identify whether bodyweight influences bioavailability, clearance and/or volume of distribution, future analysis including data on intravenously administered lamivudine is needed.

SUBMITTER: Janssen EJH

PROVIDER: S-EPMC5427247 | biostudies-literature | 2017 Jun

REPOSITORIES: biostudies-literature

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Publications

Dose evaluation of lamivudine in human immunodeficiency virus-infected children aged 5 months to 18 years based on a population pharmacokinetic analysis.

Janssen Esther J H EJH Bastiaans Diane E T DET Välitalo Pyry A J PAJ van Rossum Annemarie M C AMC Jacqz-Aigrain Evelyne E Lyall Hermione H Knibbe Catherijne A J CAJ Burger David M DM

British journal of clinical pharmacology 20170214 6

<h4>Aim</h4>The objectives of this study were to characterize age-related changes in lamivudine pharmacokinetics in children and evaluate lamivudine exposure, followed by dose recommendations for subgroups in which target steady state area under the daily plasma concentration-time curve (AUC<sub>0-24h</sub> ) is not reached.<h4>Methods</h4>Population pharmacokinetic modelling was performed in NONMEM using data from two model-building datasets and two external datasets [n = 180 (age 0.4-18 years, ...[more]

PMID: 28079918

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Project description:BackgroundUp to 15% of deaths of people living with HIV is attributable to meningeal cryptococcosis, with nearly 75% occuring in sub-Saharan Africa. Although rare in children, it is a major cause of morbidity and mortality in people living with HIV. A strong association between cryptococcal antigenemia and the development of meningeal cryptococcosis has been shown in adults. Thus, in 2018, the World Health Organization published an updated version of its guidelines for the diagnosis, prevention and management of cryptococcal infection in adults, adolescents and the HIV-infected child.GoalTo determine the prevalence of cryptococcal antigenemia and to identify its determinants in children infected with HIV.MethodsAn analytical cross-sectional study was carried out at the approved treatment center of Laquintinie hospital in Douala over a period of 4 months. Children were recruited consecutively after informed parental consent. Cryptococcal antigenemia and CD4 assay were performed using a Cryptops® immunochromatographic rapid diagnostic test and flow cytometry, respectively. The data collected included the socio-demographic, clinical and paraclinical variables of the children, as well as their antecedents. Data analysis was performed using Epiinfo software version 3.1 and SPSS 21.0. The significance threshold was set at 5%.ResultsA total of 147 children were enrolled. The mean age was 9.8 ± 4.09 years. The majority were on antiretroviral therapy (142, 96.60%). Only 13 (8.80%) were in severe immunosuppression. No child showed signs of meningeal cryptococcosis. The prevalence of cryptococcal antigenemia was 6.12%. Severe immunosuppression [OR: 10.03 (1.52-65.91), p = 0.016] and contact with pigeons [OR: 9.76 (1.14-83.65), p = 0.037] were independent factors significantly associated with the carriage of the cryptococcal antigen.ConclusionWe recommend screening for cryptococcal antigenemia and routine treatment with fluconazole of all HIV positive children with cryptococcal antigen whether symptomatic or not.

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Dataset Information

Dose evaluation of lamivudine in human immunodeficiency virus-infected children aged 5 months to 18 years based on a population pharmacokinetic analysis.

Aim

Methods

Results

Conclusion

Publications

Dose evaluation of lamivudine in human immunodeficiency virus-infected children aged 5 months to 18 years based on a population pharmacokinetic analysis.

Similar Datasets

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