Evaluation of Praziquantel Exposures in Children Dosed Using Different Body Weight Estimation Methods
Authors: Toyoshima Junko , Abdel-Rahman Susan , Bonate Peter 
Published: February 2025

Objectives: Weight-based dosing is difficult to accomplish in settings where weighing scales are unavailable, including many regions where schistosomiasis treatment is needed. However, the accuracy of pediatric weight-estimation strategies can vary widely. We aimed to simulate and compare praziquantel exposures that result from the use of various weight estimation methods.Methods: Sixteen body weight estimation methods were applied to a multinational dataset of children (n=1199; 2 to < 7 years old) in whom anthropometric measures were collected. These methods included ten age-based approaches, three length-based approaches, and three combined length and habitus (mid-upper arm circumference) approaches [1, 2]. The dosing regimen of 50 mg/kg, submitted to the European Medicines Agency (EMA) for S. mansoni infection, was utilized, and the actual drug dose was determined based on the number of 150 mg tablets specified by the manufacturer [3]. Utilizing an existing population pharmacokinetic (PK) model for praziquantel, characterized by a two-compartment disposition with allometric scaling and a dual first-order and transit absorption model [4], praziquantel exposures [maximum concentration (Cmax) and area under the concentration-time curve (AUC)] were simulated using NONMEM software after a single dose administration with the calculated dose. Results: The number of tablets based on the actual body weight was 3 - 7. It remained consistent (4 - 9) by age for its estimation methods and varied to a greater extent (1 - 17) with length- and combined approach. The summarized coefficient of variation (CV) by each estimation method was comparable across all methods with 64.0% - 77.9%, 63.6% – 77.4% and 62.9% – 79.3% for AUC and 70.7% - 96.0%, 71.4% - 94.2% and 70.5% - 96.8% for Cmax in the actual body weight based, age-based approach and length- and combined approach, respectively. The median CV by individuals accounting for the difference in estimation methods was only 5.6% and 5.9% for AUC and Cmax, respectively.Conclusions: Our findings suggest that, for praziquantel, inaccuracies introduced with pediatric weight estimation are eclipsed by the interindividual variability in PK for the drug. While this offers some flexibility in weight estimation strategy in praziquantel dose setting, these findings may not carry over to drugs with a narrower therapeutic index or a lower magnitude of interindividual variability.Citations: [1] Abdel-Rahman SM, Ridge A, Kearns GL. Estimation of body weight in children in the absence of scales: a necessary measurement to insure accurate drug dosing. Arch Dis Child. 2014 Jun;99(6):570-4.[2] Wells M, Goldstein LN, Bentley A. A systematic review and meta-analysis of the accuracy of weight estimation systems used in paediatric emergency care in developing countries. Afr J Emerg Med. 2017;7(Suppl):S36-S54.[3] https://www.ema.europa.eu/en/opinion-medicine-use-outside-EU/human/arpraziquantel[4] Falcoz C, Guzy S, Kovač J, et al. R-praziquantel integrated population pharmacokinetics in preschool- and school-aged African children infected with Schistosoma mansoni and S. haematobium and Lao adults infected with Opisthorchis viverrini. J Pharmacokinet Pharmacodyn. 2022 Jun;49(3):293-310.