Chemical formula: C₈H₁₅NO₃ Molecular mass: 173.105 g/mol PubChem compound: 70912
Levacetylleucine targets underlying processes of neurological dysfunction. Nonclinical studies demonstrated that levacetylleucine corrects energy metabolism, including improving adenosine triphosphate production.
After oral administration, levacetylleucine is rapidly absorbed. Median time to maximum concentration (Cmax), tmax, is 1 hour (ranging from 0.5 to 2.5 hours). Mean, dose-normalised (per gram of levacetylleucine) Cmax and area under the curve from time 0 to 24 hours (AUC0-24hrs) were 4 mcg/mL/g and 9 h*mcg/mL/g. The absolute oral bioavailability is unknown.
No studies on food effect on absorption have been conducted.
The mean (standard deviation [SD]) volume of distribution at steady state (Vss) was 253 (125) L. Levacetylleucine is taken up by ubiquitously expressed monocarboxylate transporters, thereby delivering levacetylleucine to all tissues including the central nervous system.
The mean (SD) clearance is 139 (59) L/h. The estimated half-life is around 1 hour. No or only minor accumulation was observed after repeat administration.
There were no clinically significant differences in the PK of levacetylleucine based on age (range: 6-67 years), sex, race/ethnicity or body weight (range: 20.5-98.4 kg).
The effect of renal or hepatic impairment on the PK of levacetylleucine has not been studied.
In vitro studies showed that levacetylleucine, at therapeutic concentrations, does not significantly inhibit the enzyme activity of cytochrome P450 (CYP450) isoforms. Levacetylleucine does not have induction potential towards CYP450 enzymes.
In vitro, levacetylleucine inhibited the efflux transporters P-glycoprotein (P-gp), breast cancer resistance protein (BCRP) or bile salt export pump (BSEP).
Levacetylleucine is a substrate and an in vitro inhibitor of organic anion transporter (OAT)1 and OAT3. The likelihood of clinically meaningful drug interactions is considered low.
Non-clinical data reveal no special hazard for humans based on conventional studies of safety pharmacology, repeated dose toxicity and genotoxicity.
No effect on fertility was seen in rats at doses up to 1 000 mg/kg/day (1.5- to 2.3-fold human exposure). In embryofoetal development studies, levacetylleucine did not induce adverse developmental effects at doses up to 1 000 mg/kg/day in rats (2.0-fold human exposure). In rabbits, external and skeletal malformations were observed at 1 250 mg/kg/day (7.1-fold of human exposure) with a no observed adverse effect level of 675 mg/kg/day (4.9-fold human exposure). No adverse effects were observed in a pre- and postnatal development study in rats at doses up to 1 000 mg/kg/day.
No carcinogenicity studies have been conducted. The carcinogenic risk is unknown.
© All content on this website, including data entry, data processing, decision support tools, "RxReasoner" logo and graphics, is the intellectual property of RxReasoner and is protected by copyright laws. Unauthorized reproduction or distribution of any part of this content without explicit written permission from RxReasoner is strictly prohibited. Any third-party content used on this site is acknowledged and utilized under fair use principles.