Optimized Sampling Strategies for Isoniazid in East Asian Pediatric Populations Using Population Pharmacokinetics-Informed Approaches

Objective: Isoniazid exposure in vivo is significantly affected by NAT2 genotypes and has ethnic differences. To optimize the sampling strategy for isoniazid in East Asian pediatric populations. We employed a model-informed optimization approach based on INH population pharmacokinetic (PopPK) models. Methods: We selected PopPK models for children and East Asian adults and optimized the sampling strategy using PopED (Population Experimental Design), a method that helps identify the most efficient sampling points for maximizing parameter estimation accuracy. Virtual patients with varying NAT2 phenotypes were created, and real-world pediatric scenarios were evaluated using questionnaire data, sampling windows, and stochastic simulations. Results: From eight analyzed models (four for East Asian adults and four for non-East Asian pediatrics), we simplified two over-parameterized models using lumping without loss of performance. The optimized clinical sampling strategy involved collecting samples at 0.25 [0-0.5], 1.5 [1-2], 6 [3-8], 12 [9-14], and 24 [22-24] hours post-dose. Simulation verification showed that re-estimated major PK parameters had acceptable relative biases and relative standard error (<30%). Conclusion: Traditional adult sampling strategies are inadequate for East Asian pediatric populations. A tailored strategy involving up to five samples can accurately estimate INH PopPK parameters and should be considered for clinical implementation to optimize treatment and reduce patient sampling burden.