Modafinil acid (code name CRL-40467), also known as modafinilic acid or modafinil carboxylate, is one of the two major metabolites of modafinil – the other being modafinil sulfone.[1] Modafinil acid is also a metabolite of the modafinil prodrug, adrafinil, and the (R)-(–)-enantiomer is a metabolite of armodafinil, the (R)-(–)-enantiomer of modafinil.[2] Between 30 - 60% of modafinil is converted to modafinil acid and its half life is roughly half that of modafinil (about 7 hours).[3] Modafinil acid seems to be inactive,[4] and similarly to modafinil sulfone, does not appear to contribute to the wakefulness-promoting/psychostimulant effects of modafinil.[5][6][7]
In the breakdown process of modafinil, modafinil is primarily hydrolyzed by an esterase or amidaseenzyme into modafinil acid.[8] The apparent clearance of modafinil acid is significantly higher than that of modafinil, following the hypothesis that metabolism increases the polarity and the clearance of modafinil.[9]
^Sousa A, Dinis-Oliveira RJ (2020). "Pharmacokinetic and pharmacodynamic of the cognitive enhancer modafinil: Relevant clinical and forensic aspects". Substance Abuse. 41 (2): 155–173. doi:10.1080/08897077.2019.1700584. PMID31951804. S2CID210709160.
^Wong YN, King SP, Simcoe D, Gorman S, Laughton W, McCormick GC, Grebow P (March 1999). "Open-label, single-dose pharmacokinetic study of modafinil tablets: influence of age and gender in normal subjects". Journal of Clinical Pharmacology. 39 (3): 281–288. doi:10.1177/009127009903900312. PMID10073328. S2CID30258993.
^Wong YN, Wang L, Hartman L, Simcoe D, Chen Y, Laughton W, et al. (October 1998). "Comparison of the single-dose pharmacokinetics and tolerability of modafinil and dextroamphetamine administered alone or in combination in healthy male volunteers". Journal of Clinical Pharmacology. 38 (10): 971–978. doi:10.1002/j.1552-4604.1998.tb04395.x. PMID9807980. S2CID32857213.
^Robertson P, Hellriegel ET, Arora S, Nelson M (January 2002). "Effect of modafinil on the pharmacokinetics of ethinyl estradiol and triazolam in healthy volunteers". Clinical Pharmacology and Therapeutics. 71 (1): 46–56. doi:10.1067/mcp.2002.121217. PMID11823757. S2CID21552865.