According to wiki, 98% of pregabalin is excreted unchanged. The body doesn't have a metabolic pathway to cope with it.
Glycine supplementation increases metabolism and excretion of aspirin and benzoic acid, and high aspirin doses suppress plasma glycine. Coadministration of nicotinic acid and aspirin yields higher plasma NA levels, presumably due to competition for limited glycine conjugation capacity. It appears glycine availabilty is rate-limiting for excretion of drugs metabolized via glycine conjugation. The last link, which I've only skimmed, appears to offer an novel rationale for why this rate limitation evolved: glycine also serves as a neurotransmitter. Indeed, many of the effects of aspirin intoxication may be due to CNS hypoglycinemia.
Patel, D. K., et al. "Depletion of plasma glycine and effect of glycine by mouth on salicylate metabolism during aspirin overdose." Human & experimental toxicology 9.6 (1990): 389-395.
Ding, Reinhard W., et al. "Pharmacokinetics of nicotinic acid–salicylic acid interaction." Clinical Pharmacology & Therapeutics 46.6 (1989): 642-647.
Gregus, Z., et al. "Dependence of glycine conjugation on availability of glycine: role of the glycine cleavage system." Xenobiotica 23.2 (1993): 141-153.
Beyoğlu, Diren, and Jeffrey R. Idle. "The glycine deportation system and its pharmacological consequences." Pharmacology & therapeutics 135.2 (2012): 151-167.
As nicotinic acid + salicylate has such interesting synergies in longevity promotion (CVD prevention, AMPK activation, NAD+/Sirtuin activation), the whole glycine issue is one I've mulled over for the past couple months (as glycine itself has so many attractive qualities). Right now, it seems wisest to me to take GLY separate from NA+SA and hope that excess GLY is metabolized to pyruvate (a nice H2O2 scavenger) before the evening NA+SA.
Edited by Darryl, 15 April 2014 - 07:50 PM.