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Pharmacokinetics of ascending doses of ivermectin in Trichuris trichiura-infected children aged 2-12 years

Schulz, Jessica D. and Coulibaly, Jean T. and Schindler, Christian and Wimmersberger, David and Keiser, Jennifer. (2019) Pharmacokinetics of ascending doses of ivermectin in Trichuris trichiura-infected children aged 2-12 years. The journal of antimicrobial chemotherapy, 74 (6). pp. 1642-1647.

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Abstract

Yearly, millions of children are treated globally with ivermectin mainly for neglected tropical diseases. Anatomical, physiological and biochemical differences between children and adults may result in changes in pharmacokinetics. However, paediatric pharmacokinetic data of ivermectin are lacking.; In the framework of a randomized controlled dose-finding trial in rural Côte d'Ivoire, Trichuris trichiura-infected pre-school-aged children (PSAC, 2-5 years) and school-aged children (SAC, 6-12 years) were assigned to 100 or 200 μg/kg and 200, 400 or 600 μg/kg ivermectin, respectively (ISRCTN registry no. ISRCTN15871729). Capillary blood was collected on dried blood spot cards until 72 h post-treatment. Ivermectin was quantified by LC-MS/MS, and pharmacokinetic parameters were evaluated by non-compartmental analysis.; C max and AUC increased in PSAC and SAC with ascending doses and were similar in both age groups when the current standard dose (200 μg/kg) was administered (∼23 ng/mL and ∼350 ng×h/mL, respectively). PSAC with lower BMI were associated with significantly higher AUCs. AUC and Cmax were ∼2-fold lower in children compared with parameters previously studied in adults, whereas body weight-adjusted CL/F (∼0.35 L/h/kg) was significantly higher in children. Tmax (∼6 h), t1/2 (∼18 h), mean residence time (MRTINF) (∼28 h) and V/F (∼8 L/kg) were similar in all paediatric treatment arms.; A positive association of AUC or Cmax with dose was observed in both age groups. Undernutrition might influence the AUC of ivermectin in PSAC. Ivermectin shows a lower exposure profile in children compared with adults, highlighting the need to establish dosing recommendations for different age groups.
Faculties and Departments:09 Associated Institutions > Swiss Tropical and Public Health Institute (Swiss TPH)
09 Associated Institutions > Swiss Tropical and Public Health Institute (Swiss TPH) > Department of Medical Parasitology and Infection Biology > Helminth Drug Development (Keiser)
UniBasel Contributors:Schulz, Jessica and Coulibaly, Jean and Schindler, Christian and Wimmersberger, David and Keiser, Jennifer
Item Type:Article, refereed
Article Subtype:Research Article
Publisher:Academic Press
ISSN:0305-7453
Note:Publication type according to Uni Basel Research Database: Journal article
Language:English
Identification Number:
Last Modified:10 Jul 2019 12:49
Deposited On:10 Jul 2019 12:49

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