Amiparen-10 Mechanism of Action

Pharmacology: The value of AMIPAREN as a source of amino acids in the nutritional support was assessed in hyperalimentation therapy using normal rate and insulted rats.
AMIPAREN promptly improved and maintained nitrogen balance and exhibited a pronounced nitrogen sparing effect in these models.
The solution promoted synthesis of plasma total protein and albumin.
The urinary 3-methylhistidine/creatinine ratio, an indicator of protein catabolism in the muscle under insult, was low after infusion treatment, indicating a very potent inhibitory effect of the solution on muscle protein breakdown.
The plasma concentrations of free amino acids including branched-chain amino acids showed minor fluctuation during infusion treatment. Amino acid metabolism was judged to be steady during AMIPAREN therapy.
CLINICAL STUDIES: Clinical studies of AMIPAREN were conducted in a total of 546 patients undergoing central of peripheral venous nutritional management.
These studies provided evidence of the high clinical value of the solution as a source of amino acids in terms of major protein metabolism-related indexes including nitrogen balance, serum total protein and albumin levels, rapid turnover protein level and urinary 3-methylhistidine/creatinine ratio.
Adverse reactions and Abnormal Laboratory Values: In 546 patients treated, 17 cases of side effects were reported, Complaints included vascular pain (0.4%) and nausea and vomiting (0.4%). Abnormal laboratory tests showed an increase in GOT and/or GPT (0.7%), an increase in BUN (0.5%) and an increase in total bilirubin (0.4%).
Pharmacokinetics: ¹⁴C-Amino acids formulated in AMIPAREN were readily taken up into plasma protein fraction after intravenous infusion in all normal rats at 3, 7 and 57 weeks of age. The radioactivity was distributed in higher concentrations to protein fractions of the spleen, liver and kidneys as well as muscles.
Respiratory excretion accounted for 37.1%-44.2% over 72 hours postinfusion. As other major routes of elimination, 3.9%-5.2% and 1.2%-3.1% of the radioactivity were recovered from the urine and feces, respectively. Amino acid fractions in the urine contained only 1.1%-1.5% of the amino acids given. The overall retention of amino acids in the body amounted to more than 98.5% of the dose.
Toxicology: Acute toxicity: LD₅₀ values (intravenous, infusion rate: 4 mL/minute): 170 mL/kg male rabbits; 120 mL/kg female rabbits.
Long term toxicity studies (rabbits, intravenous, 13 weeks and 26 weeks, an antigenicity study and a local irritation study did not reveal any AMIPAREN related specific toxic symptoms).