Dataset Information

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

ABSTRACT:

Background

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.

Methods

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??g/kg and 200, 400 or 600??g/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.

Results

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??g/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.

Conclusions

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.

SUBMITTER: Schulz JD

PROVIDER: S-EPMC6524481 | biostudies-literature | 2019 Jun

REPOSITORIES: biostudies-literature

ACCESS DATA

Publications

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

Schulz Jessica D JD Coulibaly Jean T JT Schindler Christian C Wimmersberger David D Keiser Jennifer J

The Journal of antimicrobial chemotherapy 20190601 6

<h4>Background</h4>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.<h4>Methods</h4>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 scho ...[more]

PMID: 30859185

Similar Datasets

Project description:BackgroundSoil-transmitted helminthiasis affects almost 2 billion people worldwide in tropical climates. Preventive chemotherapy, using the benzimidazoles (albendazole and mebendazole) is the current main recommended control strategy. Nevertheless, there is limited efficacy of these drugs against hookworm infection and, to a greater extent, against trichuriasis. We describe a protocol for a trial investigating the efficacy and safety of the co-administration of ivermectin and albendazole against trichuriasis.MethodsA double-blind, placebo-controlled randomized controlled trial will be conducted in three countries (Côte d'Ivoire, Tanzania and Lao PDR) with the aim to determine the efficacy, safety and extended effects of co-administered ivermectin and albendazole compared to standard albendazole monotherapy. We will enroll 600 participants aged 6-60 years in each setting. The primary outcome is cure rate (CR) against Trichuris trichiura infection as assessed by Kato-Katz 14-21 days after treatment. Secondary outcomes include CRs against concomitant soil-transmitted helminth (STH) infections (Ascaris lumbricoides, hookworm and Strongyloides stercoralis) and egg reduction rates (ERRs) against STH at 14-21 days, 180 days and 360 days. Tolerability of treatment, infection status assessed by polymerase chain reaction (PCR), and potential benefits of deworming on nutritional and morbidity indicators will be assessed. The primary analysis will include an available-case set and use logistic regression models adjusted for age, sex and weight.DiscussionThis trial will provide robust results on the efficacy and safety of co-administration of ivermectin and albendazole with the aim to better inform WHO recommendations on control of STHs. Furthermore, secondary and explanatory outcomes will provide direct evidence on the extended effects of combination therapy and insight on the relationship between nutrition and morbidity parameters and infection status and intensity.Trial registrationNCT03527732 (date assigned: 17 May 2018).

Project description:Background: Infections with soil-transmitted helminths (STHs) predominantly affect impoverished populations in tropical environments. The periodic administration of single dose benzimidazoles (i.e., albendazole, mebendazole) to at-risk individuals in endemic regions is at the center of STH control strategies. Given the low efficacy of these drugs against trichuriasis, investigation of drug combinations including moxidectin and ivermectin has recently been initiated, yet the identification of the best treatment option requires more research. We present the protocol for a trial investigating the efficacy and safety of co-administered moxidectin and albendazole compared to co-administered ivermectin and albendazole against Trichuris trichiura. Methods: We will conduct a randomized controlled trial enrolling 540 T. trichiura-infected adolescents aged 12-19 years on Pemba Island (Tanzania). The primary objective is to demonstrate non-inferiority of orally co-administered single-dose moxidectin (8 mg)/albendazole (400 mg) compared to orally co-administered single-dose ivermectin (200 µg/kg)/albendazole (400 mg) in terms of egg reduction rates (ERRs) against T. trichiura infections assessed by Kato-Katz at 14-21 days post-treatment. Secondary objectives include the assessment of the drug combinations' superiority compared to their respective monotherapies, of the cure rates (CRs) against T. trichiura, and the safety and tolerability of all treatments, as well as CRs and ERRs against concomitant STH infections ( Ascaris lumbricoides and hookworm). Potential effects of the treatment regimens on follow-up prevalences of STH at 5-6 weeks and 3 months post-treatment, infection status derived by quantitative polymerase chain reaction (qPCR), and pharmacokinetic/ pharmacodynamic parameters will also be assessed. Furthermore, a subsample of stool specimens will be analyzed by an updated version of the FECPAK G2 platform. Conclusions: Results from this trial will help to inform decision- and policymakers on which anthelminthic combination therapy might improve existing deworming programs and provide a valuable adjunct tool for interrupting STH transmission. Clinicaltrials.govregistration: NCT04700423 (07/01/2021).

Project description:IntroductionSoil-transmitted helminth (STH) infections are predominately controlled by providing children with preventive chemotherapy with either albendazole or mebendazole. However, neither has a high efficacy against Trichuris trichiura. This low efficacy limits the overall effectiveness of the current STH control programmes against T. trichiura. It has been demonstrated that co-administering ivermectin with albendazole or mebendazole significantly increases the efficacy of current treatments, which may increase the overall effectiveness of control programmes.MethodsUsing a STH transmission mathematical model, we evaluated the potential impact of co-administering ivermectin with albendazole or mebendazole to treat T. trichiura within a preventive chemotherapy programme targeting children (2-15 year olds). We evaluated the impact in terms of reduction in prevalent infections, mean worm burden, and prevalence of heavy infections.ResultsAlthough the current treatment strategy reduced T. trichiura worm burden and prevalence of heavy infections, due to their poor efficacy the long term impact of preventive chemotherapy for children was smaller compared to the other STH. Co-administering ivermectin increased the projected impact of the preventive chemotherapy programme in terms of all three of the explored metrics, practically in high transmission settings. Furthermore, ivermectin co-administration greatly increased the feasibility of and timeframe for breaking transmission.ConclusionsCo-administering ivermectin notably increased the projected impact of preventive chemotherapy in high transmission settings and increased the feasibility for breaking transmission. This has important implications for control programmes, some of which may be shifting focus from morbidity control to interruption of transmission, and some of which may be logistically unable to provide preventive chemotherapy twice a year as recommended. However, the benefit of co-administering ivermectin is limited by the fact that 2-5 year olds are often ineligible to receive treatment.

Dataset Information

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

Background

Methods

Results

Conclusions

Publications

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

Similar Datasets

OmicsDI is part of the ELIXIR infrastructure

Tweets