Pharmacokinetics and brain entry of alaptide, a novel nootropic agent, in mice, rats and rabbits

Abstract

Pharmacokinetics of a novel nootropic agent, alaptide, have been examined in plasma and brain of mice, rats and rabbits following an intravenous dose (1 mg kg-1). First-order equilibration rate constants between plasma and brain (kBO) were calculated by a two-compartment model with a linked compartment (brain). Brain alaptide equilibrates rapidly with the central compartment in mice and rats due to the high kBO/beta ratio. In rabbits the equilibration is much slower (kBO/beta approximately 1). Partition coefficients between brain and plasma calculated from areas under the brain and plasma concentration-time curves, are 0.479, 0.549 and 0.864, in mice, rats and rabbits, respectively.

Rapid Screening of Mupirocin Skin Permeation Modification by Micronized and Nanonized Alaptide

“…Metabolic studies in rats showed that alaptide is readily absorbed from the gastrointestinal tract and penetrates the blood-brain barrier [17,21]. It is excreted unchanged, mostly via urine (90%); a similar metabolic profile was also found in humans [29]. Any toxicity (acute, subchronic and chronic) as well as genotoxic, teratogenic and embryotoxic effects of alaptide were not observed [17,21,30].…”

In Vitro Permeation of Micronized and Nanonized Alaptide from Semisolid Formulations

“…Keratinocytes migrate from stratum basale to stratum spinosum and stratum granulosum to stratum corneum , where they support epidermis regeneration [15]. It is excreted unchanged, mostly via urine; a similar metabolic profile was also found in man [8, 16, 17]. No toxic effects of alaptide (including skin irritation) were observed.…”

Permeation of Indomethacin through Skin Using Nanonized Alaptide

“…Although bulk alaptide is absorbed from the gastrointestinal tract or permeates through the skin [5,12], nanonized alaptide (NALA) permeates through the skin insignificantly [12]. Alaptide is not metabolized and is excreted mostly via urine [13]. Alaptide demonstrated very low acute toxicity; no subchronic and chronic toxicity, genotoxic, teratogenic and embryotoxic effects were observed [5,14,15].…”