Novel Patient-Friendly Orodispersible Formulation of Ivermectin is Associated With Enhanced Palatability, Controlled Absorption, and Less Variability: High Potential for Pediatric Use.
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State: Public
Version: Final published version
License: CC BY-NC-ND 4.0
State: Public
Version: Final published version
License: CC BY-NC-ND 4.0
Serval ID
serval:BIB_6FBF4894C204
Type
Article: article from journal or magazin.
Collection
Publications
Institution
Title
Novel Patient-Friendly Orodispersible Formulation of Ivermectin is Associated With Enhanced Palatability, Controlled Absorption, and Less Variability: High Potential for Pediatric Use.
Journal
Journal of clinical pharmacology
ISSN
1552-4604 (Electronic)
ISSN-L
0091-2700
Publication state
Published
Issued date
10/2024
Peer-reviewed
Oui
Volume
64
Number
10
Pages
1295-1303
Language
english
Notes
Publication types: Journal Article ; Randomized Controlled Trial ; Clinical Trial, Phase I
Publication Status: ppublish
Publication Status: ppublish
Abstract
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 C <sub>max</sub> , AUC <sub>0-∞</sub> , and AUC <sub>0-last</sub> , 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 T <sub>max</sub> 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.
Keywords
Humans, Ivermectin/pharmacokinetics, Ivermectin/administration & dosage, Ivermectin/adverse effects, Male, Cross-Over Studies, Female, Biological Availability, Administration, Oral, Adult, Tablets, Antiparasitic Agents/pharmacokinetics, Antiparasitic Agents/administration & dosage, Antiparasitic Agents/adverse effects, Area Under Curve, Young Adult, Middle Aged, STROMECTOL, TIP‐based technology, bioavailability, children, ivermectin, orodispersible formulation (ODT), palatability, pharmacokinetics, variability
Pubmed
Web of science
Open Access
Yes
Create date
14/06/2024 14:32
Last modification date
01/10/2024 7:15