Getting drug doses right in children with tuberculosis (TB)

H. McIlleron
2014 International Journal of Infectious Diseases  
New drugs that could revolutionize the treatment of drugsensitive and drug-resistant TB are imminently available. Moreover recent research of pharmacokinetic-pharmacodynamic relationships in adults suggests that the doses of some currently used drugs should be changed. It is imperative that children access these improvements to TB treatment without delay. It is likely that children will respond well to a TB regimen if given drug formulations and doses that achieve comparable pharmacokinetics to
more » ... those in adults. Recent changes to the WHO-dosing guidelines for the first line TB drugs in children acknowledge that the traditional approach to pediatric dosing (using mg/kg doses approximating those in adults) resulted in under-dosing of children for decades. Efficient pharmacokinetic studies are necessary to support safe and effective doses for children. Contemporary modelbased pharmacometric analyses facilitate efficient studies, pooling of data across different studies, and prediction of pragmatic dosing approaches. Pediatric studies designed to describe the pharmacokinetics of new drugs need to be conducted during drug development, typically as soon as phase 2b studies in adults have been completed. The studies should include sufficient data in children across the range of ages, and should preferably be conducted in the target pediatric population using appropriate child-friendly formulations, which should be developed early. Treatment preparation and administration methods practiced by caregivers of infants and young children could affect the stability and bioavailability of the drugs administered. There is little knowledge of these practices, or treatment acceptability and taste preferences, which should be taken into account when developing suitable formulations and pragmatic advice on dose administration. Drug-drug interactions complicate the management of HIV and other comorbid conditions in children with TB. As the magnitude of pharmacokinetic drug-drug interactions may not be predicted by adult studies, studies in children are required to guide dose adjustments. The optimization of doses and formulations for children will improve care and cannot continue to be neglected. http://dx.Professor Kampmann leads a research team of clinicians and scientists in the UK and West Africa. Her group has been working on the difficult problem of childhood tuberculosis and has evaluated immune responses to natural infection and vaccination, including novel diagnostics. Her overview presentation today will summarise recent accomplishments in the development of new vaccine against TB, why these might or might not work and what lessons can be learned from the recent Phase IIb trial of a new anti-TB vaccine in South Africa, which unfortunately-or maybe predictively-did not show any protective efficacy in young children. She will present her thoughts on where this leaves the field now and what the next steps might be. She would not expect that everyone agrees. http://dx.
doi:10.1016/j.ijid.2014.03.535 fatcat:5wdbp4eenfdhlcnnpselvwa2xa