Peer-reviewed article
Repeated-Dose High-Dose Ivermectin Pharmacokinetics and Safety in Children with Acute Dengue
Keswadee Lapphra, Dumrong Mairiang, Joel Tärning, Dararat Prayongkul, Chunya Puttikhunt et al. ·
Summary
Written by AI, not yet AICS's view · claude-haiku-4-5-20251001This study examined how children's bodies process high-dose ivermectin, an experimental treatment for dengue fever. Twenty-four Thai children aged 1-15 years with acute dengue received ivermectin for 3 days at two different dose levels, and researchers measured drug levels in their blood and monitored safety. Most adverse events were consistent with dengue itself, though six children had low white blood cell counts that resolved without treatment. The study was not designed to test whether ivermectin actually treats dengue, only to understand how it moves through children's bodies and whether it is safe.
Key points
- All 24 children completed the study and experienced at least one adverse event, most consistent with acute dengue
- Six participants (25%) had grade 4 neutropenia (low white blood cells), but all were clinically well and required no specific treatment
- Drug exposure increased with dose: median AUC was 1316.49 ng·h/mL at 400 μg/kg and 2129.41 ng·h/mL at 600 μg/kg
- No clear relationship was found between ivermectin exposure and viremia or NS1 (viral marker) trajectories in the first 48 hours
- No serious adverse events were assessed as related to ivermectin
Limitations
The study was explicitly not designed or powered to evaluate whether ivermectin actually works against dengue or improves clinical outcomes. The small sample size (24 children) and open-label design without a control group limit what can be concluded about the drug's effectiveness.
Abstract
Ivermectin has shown anti-dengue virus activity in experimental systems, and an adult dengue trial found faster clearance of circulating non-structural protein 1 (NS1) without improvement in viremia or clinical outcomes. Pediatric pharmacokinetic and safety data for repeated high-dose regimens remain limited. We characterized repeated-dose ivermectin pharmacokinetics and safety in children with acute uncomplicated dengue weighing ≥15 kg. In this prospective, open-label, sequential dose-escalation study, children aged 1–15 years who presented within 72 h of fever onset and met the protocol laboratory-confirmation criteria for dengue received ivermectin 400 or 600 μg/kg once daily for 3 days. Noncompartmental analyses estimated exposure and peak concentrations from intensive plasma sampling. Exploratory analyses examined associations between exposure and viremia and NS1 trajectories during the first 48 h after dose 1; the study was not designed or powered to evaluate antiviral efficacy. All 24 children completed follow-up and experienced at least one adverse event; most events were consistent with acute dengue. Six participants (25%) experienced serious adverse events consisting of grade 4 neutropenia; all participants were clinically well, required no neutropenia-specific treatment, and showed improvement at the next available assessment or follow-up. No serious adverse event was assessed as related to ivermectin. One asymptomatic grade 1 QTc-prolongation adverse event was recorded and required no intervention. Exposure increased with dose: median 0–48-h area under the concentration–time curve (AUC last ) was 1316.49 and 2129.41 ng·h/mL at 400 and 600 μg/kg, respectively, and corresponding maximum observed concentrations ( C max ) were 107.50 and 165.50 ng/mL. Dose-normalized parameters showed no clear relationship with body weight. Analyses confined to the first 48 h identified no clear exposure–response association with viremia or NS1 trajectories. In children weighing ≥15 kg with acute uncomplicated dengue, ivermectin exposure increased with administered dose, while dose-normalized AUC last and C max showed no clear relationship with body weight across the studied range. Pharmacokinetics and Pharmacodynamics of Ivermectin in Pediatric Dengue Patients (PKIDEN) therefore fills an important dengue-specific pediatric clinical pharmacology gap and provides repeated-dose exposure and safety reference data that may inform dose selection, exposure interpretation, and safety monitoring in future studies. The study was not designed to determine antiviral efficacy or clinical benefit. ClinicalTrials.gov: NCT03432442; first posted February 14, 2018.
Findings the Hub has extracted
Each claim below is labelled by its type of design and links back to this report.
- Intervention
- Repeated daily doses of ivermectin 400 or 600 μg/kg for 3 days in children with acute uncomplicated dengue
- Population
- 24 children aged 1-15 years weighing ≥15 kg, presenting within 72 hours of fever onset with laboratory-confirmed dengue
Key finding
Drug exposure increased predictably with dose escalation (400 to 600 μg/kg)