Treatment of acetaminophen poisoning. The use of oral methionine

Abstract

One hundred thirty-two cases of severe acetaminophen (paracetamol) poisoning were treated with oral methionine. Seven of 96 patients who received the antidote within ten hours of ingestion of the overdose had severe liver damage (aspartate transaminase level, greater than 1,000 IU/L), but none of these patients died. Thirty-six patients received methionine between ten and 24 hours of ingestion; severe liver damage occurred in 47%, and two patients died. The treatment protocol for oral methionine is simple, and therapy is complete within 12 hours as compared with three days for oral acetylcysteine and 20 hours for intravenous acetylcysteine. Side effects from methionine were unimportant. Oral methionine is as effective as acetylcysteine in preventing severe liver damage and death after acetaminophen overdose. However, as with acetylcysteine, it must be given within ten hours of ingestion to be effective.

Pharmacokinetic Analysis and Phase 1 Study of MRX-1024 in Patients Treated with Radiation Therapy with or without Cisplatinum for Head and Neck Cancer

“…Oral methionine has been used for the treatment of liver toxicity following acetaminophen overdose (32)(33)(34)(35)(36), arthritis (37), or AIDS-related neuropathy (38,40), but most typically, it has been administered as the L-isomer or racemic mixture. Therefore, given previously shown prolonged clearance and reduced toxicity when using the Disomer in humans compared with the L-isomer, we set about evaluating the pharmacokinetics of D-met when administered as a high-concentration oral solution (MRX-1024; refs.…”

“…If DLT was observed, then the dose would be deescalated. The reasons for this change in protocol were as follows: (a) the excellent tolerability of MRX-1024 during the normal human volunteer studies where six patients had received 50 mg/kg and six had received 100 mg/kg with no evidence for toxicity; (b) the previous 30-year experience using oral methionine for treatment of acetaminophen overdose (32)(33)(34)(35)(36); (c) the previous experience administering pharmacologic doses of L-met to patients for as long as 6 months without toxicity for the treatment of rheumatoid arthritis (37) or AIDS-related peripheral neuropathy (38,40); (d) the previous data documenting toxicity associated with D-met only after conversion to L-met with >60% of D-met excreted unchanged in humans such that treatment on this study would result in lower exposure to L-met over a shorter period of time compared with accepted treatment schedules (24-28, 31, 38, 40); and (e) the previous dose-dependent mucosal protection observed in preclinical models (23) where maximal protection was observed with peak plasma concentrations analogous to those observed at the highest dose administered to patients in the pharmacokinetic portion of the study.…”

“…Clinically, L-met has been available for decades for treatment of dermatitis using an over-the-counter preparation with a recommended dose of 200 to 400 mg orally three to four times per day. The racemic mixture may also be used to treat acetaminophen overdose, where a total oral dose of 10 g is administered over 12 hours (32)(33)(34)(35)(36). Oral methionine was also previously evaluated for treatment of rheumatoid arthritis, where 24 patients were treated with 5 or 10 g of L-met daily for 16 or 8 weeks, respectively.…”

Effect of N-acetylcysteine on the pulmonary response to endotoxin in the awake sheep and upon in vitro granulocyte function.

“…These highly reactive radicals will preferentially bind to glutathione, thereby converting it to a nontoxic conjugate of cysteine, but the detoxifying mechanisms can be exhausted ifcysteine or glutathione stores are depleted (22). The sulfhydryl bond of cysteine seems to be the important element because similar results have been obtained with methionine and cysteamine (23,24). These compounds, along with NAC, are thought to work by providing substrate to replenish glutathione stores, or by competitively binding directly to the free radical species.…”

Hepatoprotective effect of DL-methionine on diclofenac-induced hepatotoxicity in albino rats: an experimental study

“…5 Hepatocytes death is a characteristic presentation that occurs in case of liver injury, mainly due to the fibrosis and necrosis, which are generally prevented by NAcetylcysteine, particularly in case of Acetaminophen toxicity. [6][7][8][9]3 Similarly, the essential amino acid, Methionine has also found to be a beneficial hepatoprotective agent which is also been proposed for the treatment of certain disease condition. 3,[10][11][12] Hence, the present study was taken up to demonstrate its hepatoprotective effect on Diclofenacinduced hepatotoxicity.…”