Background
Soil-transmitted helminth infections, including trichuriasis, remain a major public health challenge in many tropical and subtropical low-income countries, including Africa. A recent study on exposure-response efficacy analysis of albendazole and ivermectin combination therapy among adolescents in Côte d’Ivoire and Tanzania reported that the pharmacokinetic (PK) profile of ivermectin was best described by a one-compartment model with first-order absorption (1). However, the model was constrained due to the small sample size and sparse sampling. Unlike the conventional (frequentist) population PK (popPK) modeling method, a Bayesian approach can provide accurate estimates and reliable error estimates in small datasets or sparse sampling (2). Herein, the present study aimed to conduct a Bayesian popPK analysis on ivermectin PK data.
Methods
The data used in this study were collected as part of larger studies. The details of the methodology were published elsewhere (3,4). Briefly, a randomized controlled trial among adolescents (12-19 years old) with Trichuris trichiura infections was conducted in Côte d’Ivoire and Tanzania, wherein participants were randomly assigned to receive ivermectin and/or albendazole. Bayesian popPK analysis was conducted in Stan. Weakly informative priors were constructed from the literature using Chebyshev’s inequality.
Results
A total of 24 participants (66.7% from Tanzania, 33.3% females) were included in the analysis. The mean age of the participants was 15.5 ± 1.9 years. A one-compartment PK model with first-order absorption and first-order elimination was fitted to the data. The model was parameterized as ka (absorption rate constant), Cl/F (apparent clearance), and V/F (apparent volume of distribution). As shown in Table 1, the typical apparent volume of distribution was 168.40 L, and the typical apparent clearance was 7.44 L/h. Posterior predictive checks suggested good agreement between observed and fitted concentrations.
Conclusion
The one-compartment Bayesian PopPK model adequately described the pharmacokinetics of ivermectin among adolescents infected with Trichuris trichiura in Côte d’Ivoire and Tanzania.
References
- Ajayi DT, Orherhe OM, Pillai G, Mouksassi S, Steffens B, Bräm D, et al. Pharmacometric Analysis to Describe Pharmacokinetics and Exposure-Efficacy Response of Ivermectin in Adolescents Infected with Trichuris trichiura. The Journal of Clinical Pharmacology. 2025;65(4):433–40.
- Wakefield J. The Bayesian analysis of population pharmacokinetic models. Journal of the American Statistical Association. 1996;91(433):62–75.
- Sprecher VP, Coulibaly JT, Hürlimann E, Hattendorf J, Keiser J. Efficacy and safety of moxidectin-albendazole and ivermectin-albendazole combination therapy compared to albendazole monotherapy in adolescents and adults infected with Trichuris trichiura: a randomized, controlled superiority trial. Clinical Infectious Diseases. 2023;77(9):1294–302.
- Welsche S, Mrimi EC, Hattendorf J, Hürlimann E, Ali SM, Keiser J. Efficacy and safety of moxidectin and albendazole compared with ivermectin and albendazole coadministration in adolescents infected with Trichuris trichiura in Tanzania: an open-label, non-inferiority, randomised, controlled, phase 2/3 trial. The Lancet infectious diseases. 2023;23(3):331–40.
