Pharmacokinetic Characterization and Comparative Bioavailability of an Innovative Orodispersible Fixed-Dose Combination of Ivermectin and Albendazole: A Single Dose, Open Label, Sequence Randomized, Crossover Clinical Trial in Healthy Volunteers

Algorta, Jaime; Krolewiecki, Alejandro; Pinto, Filipe; Gold, Silvia; Muñóz, José

doi:10.3389/fphar.2022.914886

Cited by 5 publications

(1 citation statement)

References 26 publications

Supporting

Mentioning

Contrasting

Order By: Relevance

“…To facilitate weight-based regimens, which are complex in preventive chemotherapy programs, a fixed-dose formulation of albendazole with a high dose of ivermectin is currently under development (31)(32)(33). An adaptive phase II/III randomized controlled trial has been undertaken in STH endemic sites in Ethiopia, Kenya, and Mozambique to evaluate an oral fixed-dose combination of 400 mg albendazole and either 9 or 18 mg ivermectin with the goal of providing a simplified treatment formulation (33).…”

Section: Drug Combinationsmentioning

confidence: 99%

Present drugs and future perspectives in treating soil-transmitted helminthiasis

Keiser

2023

Front. Trop. Dis

View full text Add to dashboard Cite

Soil-transmitted helminthiases caused by Ascaris lumbricoides, Trichuris trichiura, and hookworm (Ancylostoma duodenale and Necator americanus) are responsible for the infection of approximately 1.5 billion people worldwide, mostly in tropical and subtropical regions. Preventive chemotherapy is the mainstay of control, which is the regular administration of anthelminthic drugs, mainly albendazole and mebendazole to at-risk populations. As benzimidazoles face a risk of developing drug resistance and have shortcomings in their therapeutic profile, efforts have been made to develop alternative anthelminthics. The aim of this review is to provide a state-of-the-art update on available treatments and ongoing efforts in Research and Development (R&D) for the three main soil-transmitted helminth infections. Recent findings on the use of drug combinations and advanced drug candidates such as oxantel pamoate and emodepside and how these drugs fulfill the target product profile will be reviewed. Lastly, progress in drug discovery will be summarized.

show abstract

Section: Drug Combinationsmentioning

confidence: 99%

Present drugs and future perspectives in treating soil-transmitted helminthiasis

Keiser

2023

Front. Trop. Dis

View full text Add to dashboard Cite

show abstract

Population Pharmacokinetics and Exposure–Response Analysis of a Fixed‐Dose Combination of Ivermectin and Albendazole in Children, Adolescents, and Adults

Algorta,

Kepha,

Krolewiecki

et al. 2024

Clin Pharma and Therapeutics

View full text Add to dashboard Cite

Trichuris trichiura is a soil‐transmitted helminth causing intestinal disease. Albendazole is the standard treatment despite its moderate efficacy, which is improved when co‐administered with ivermectin. A fixed‐dose combination adds practical advantages mainly for mass drug administration. The aim of this article is to define the population pharmacokinetic models and exposure–response of an innovative albendazole/ivermectin combination. Data were obtained from a phase I clinical trial in healthy adults and from a phase II trial in children and adolescents infected with T. trichiura. Nonlinear mixed‐effects models were built for albendazole and ivermectin using NONMEM®. Area under the curve was calculated using the empirical Bayes estimates of the pharmacokinetic parameters of each individual and used for evaluation of exposure–response between cure rate and pharmacokinetic exposure. The pharmacokinetics of albendazole was described using a two‐compartmental model with first‐order absorption and the pharmacokinetics of ivermectin was described using a two‐compartmental model with zero‐order followed by first‐order absorption. Clearance and volume of distribution increased with body weight for both albendazole and ivermectin. Day 1 area under the curve of albendazole and ivermectin from the children and adolescents treated with the combination regimens were similar to the healthy adults treated with control drugs. A flat exposure–response relationship was observed between the cure rate and drug exposure. Population pharmacokinetic of a combination of albendazole and ivermectin in children, adolescents, and adults, either healthy or infected by T. trichiura was described. The dosage selected in the phase II trial was appropriate for the subsequent phase III.

show abstract

Novel Patient‐Friendly Orodispersible Formulation of Ivermectin is Associated With Enhanced Palatability, Controlled Absorption, and Less Variability: High Potential for Pediatric Use

Dao,

Buettcher,

Golhen

et al. 2024

The Journal of Clinical Pharma

View full text Add to dashboard Cite

Ivermectin has been used since the 1980s as an anthelmintic and antiectoparasite agent worldwide. Currently, the only available oral formulation is tablets designed for adult patients. A patient‐friendly orodispersible tablet formulation designed for pediatric use (CHILD‐IVITAB) has been developed and is entering early phase clinical trials. To inform the pediatric program of CHILD‐IVITAB, 16 healthy adults were enrolled in a phase I, single‐center, open‐label, randomized, 2‐period, crossover, single‐dose trial which aimed to compare palatability, tolerability, and bioavailability and pharmacokinetics of CHILD‐IVITAB and their variability against the marketed ivermectin tablets (STROMECTOL) at a single dose of 12 mg in a fasting state. Palatability with CHILD‐IVITAB was considerably enhanced as compared to STROMECTOL. Both ivermectin formulations were well tolerated and safe. Relative bioavailability of CHILD‐IVITAB compared to STROMECTOL was estimated as the ratios of geometric means for Cmax, AUC 0‐∞, and AUC0‐last, which were 1.52 [90% CI: 1.13‐2.04], 1.27 [0.99‐1.62], and 1.29 [1.00‐1.66], respectively. Maximum drug concentrations occurred earlier with the CHILD‐IVITAB formulation, with a median Tmax at 3.0 h [range 2.0‐4.0 h] versus 4.0 h [range 2.0‐5.0 h] with STROMECTOL (P = .004). With CHILD‐IVITAB, variability in exposure was cut in half (coefficient of variation: 37% vs 70%) compared to STROMECTOL. Consistent with a more controlled absorption process, CHILD‐IVITAB was associated with reduced variability in drug exposure as compared to STROMECTOL. Together with a favorable palatability and tolerability profile, these findings motivate for further clinical studies to evaluate benefits of such a patient‐friendly ODT formulation in pediatric patients with a parasitic disease, including infants and young children <15 kg.

show abstract

Pharmacokinetic Characterization and Comparative Bioavailability of an Innovative Orodispersible Fixed-Dose Combination of Ivermectin and Albendazole: A Single Dose, Open Label, Sequence Randomized, Crossover Clinical Trial in Healthy Volunteers

Cited by 5 publications

References 26 publications

Present drugs and future perspectives in treating soil-transmitted helminthiasis

Present drugs and future perspectives in treating soil-transmitted helminthiasis

Population Pharmacokinetics and Exposure–Response Analysis of a Fixed‐Dose Combination of Ivermectin and Albendazole in Children, Adolescents, and Adults

Novel Patient‐Friendly Orodispersible Formulation of Ivermectin is Associated With Enhanced Palatability, Controlled Absorption, and Less Variability: High Potential for Pediatric Use

Contact Info

Product

Resources

About