Page 76 - JCTR-11-1

Journal of Clinical and
Translational Research Pediatric dosing of antituberculosis medicines

this study, both methods provided an excellent prediction It is important to recognize that the physiology of
of pediatric doses for antituberculosis medicines, as adults differs significantly from that of younger children
recommended by WHO and the FDA and this may be (e.g., premature neonates, neonates, and toddlers). These
an indication that the recommended pediatric doses of physiological differences lead to variations in the PK
antituberculosis by WHO and FDA are not based on per of medicines and, consequently, dosing strategies. In
kg body weight but still requires optimization. this study, there were 12 observations in children aged
≤12 months, and both methods predicted the dose with
Neonates or very young children can also be infected
by TB through adults or other unknown sources. Preterm the same level of accuracy in this age group as in older
children. However, the sample size in this study is too
and term neonates, as well as neonates with extremely low
birth weight or very low birth weight, may have entirely small to draw definitive conclusions about the impact of
different exposure of antituberculosis medicines than the age on the accuracy of dose predictions for antituberculosis
medicines using these two models.
older children. Since TB is common to all ages, clinical
trials should include very young children after safety and 5. Conclusion
efficacy of an antituberculosis medicines is established in
adults. All models are erratic and uncertainty remains in Robust PK studies are needed to determine the ‘right
the predictive power of these models therefore, dedicated dose’ for antituberculosis medicines both in adults and
35
clinical studies at least in terms of PK should be conducted children. Isoniazid dosing both in adults and children
in the neonates and toddlers. require re-evaluation considering the PK characteristics of
different acetylator categories.
Since TB is common to all ages, clinical trials should
include very young children after safety and efficacy of In this report, two simple methods to predict first-
an antituberculosis medicines is established in adults. in-pediatric dose to initiate a pediatric clinical trial for
All models are erratic and uncertainty remains in the antituberculosis medicines were evaluated. The predictive
predictive power of these models35 therefore, dedicated power of both methods are robust and accurate since more
clinical studies at least in terms of PK should be conducted than 80% observations were within 30% prediction error.
in the neonates and toddlers. Considering the accuracy of these two methods, they could
be used in clinical settings in emergency situations when
Population PK studies can be conducted with sparse clinical trial-based pediatric doses are unavailable. Both
sampling across the age groups. Many such population PK methods are straightforward to implement, demonstrating
studies for antituberculosis medicines have been conducted that simple approaches can be as accurate as more complex
with a claim that allometric scaling was used in these studies. and elaborate methods. Complexity does not necessarily
In fact, in these studies, theoretical exponents 0.75 and 1.0 guarantee greater accuracy than simplicity.
for clearance and volume distribution, respectively, were
used. Allometry is not defined by some fixed theoretical Acknowledgments
exponents. Over the years, dozens of manuscripts by the None.
experts in the field have identified the limitations of the
theoretical exponents. 36-38 It is incomprehensible that the Funding
slope or exponent of a regression line will never change
rather will remain same irrespective of the data. The No government or private source provided any funds for
exponents of allometry are data dependent and are not this research.
fixed. There are enough data and wide body weight range Conflict of interest
in a population PK study to determine the exponents for
both clearance and volume of distribution. Therefore, the The author declares no conflicts of interest.
exponents of allometry in population PK studies should be Author contributions
determined rather than fixed because there will be enough
data points and wider body weight range (children to This is a single-authored article.
adults) to determine the allometric exponent.
Ethics approval and consent to participate
The WHO and FDA recommend the dosing for
antituberculosis medicines based on weight bands. The Not applicable.
weight bands should be revaluated especially, in the
younger children since some weight bands are very wide Consent for publication
and there may be concerns with safety and efficacy. Not applicable.

Volume 11 Issue 1 (2025) 70 doi: 10.36922/jctr.24.00070