ROCMALINE, oral solution, ampoule

Indications

• Urea cycle disorders
• Hyperammonaemia types I and II
• Citrullinaemia
• Arginosuccinic aciduria
• Deficiency of N-acetyl glutamate synthetase
• Acute hyperammonaemia in carbamylphosphate synthetase deficiency
• Acute hyperammonaemia in ornithine transcarbamylase deficiency

Dosage

Children: Neonate: 100–300 mg/kg daily in 3–4 divided doses; Child (body-weight up to 40 kg): 6 mg/kg/hour; Child (body-weight 40 kg and above): 4 mg/kg/hour.

Adults: Refer to BNF for specific dosing based on condition; typically administered as 5–50 mg/kg twice daily, adjusted according to plasma ammonia concentration.

Mechanism of action

Arginine serves as a substrate for the synthesis of nitric oxide (NO), a crucial signaling molecule, and contributes to the urea cycle, facilitating the detoxification of ammonia in the liver.

Pharmacodynamics

As a precursor for nitric oxide, arginine plays a vital role in vasodilation and modulating blood flow. It also aids in protein synthesis and supports metabolic processes in the body.

Pharmacokinetics

Arginine is absorbed from the gastrointestinal tract and is distributed throughout the body. It undergoes hepatic metabolism, primarily via the urea cycle, and its half-life is influenced by renal function.

Pregnancy

Use only if clearly needed; consult specialist.

Breast-feeding

Use with caution; benefits should outweigh risks.

Storage

Store in a cool, dry place away from direct sunlight.

Formulations

• L-Arginine 500 mg tablets
• L-Arginine 1 gram tablets
• L-Arginine powder for solution
• L-Arginine 500 mg capsules
• L-Arginine 21% concentrate for solution for infusion

Dosage

Children: Refer to specific product information or clinical guidelines for pediatric dosing.

Adults: Refer to specific product information or clinical guidelines for dosing.

Mechanism of action

Drugs' mechanisms of action vary widely depending on their class and target. Common mechanisms include receptor agonism or antagonism, enzyme inhibition, or modulation of ion channels. For example, many analgesics work by inhibiting cyclooxygenase enzymes, reducing the synthesis of prostaglandins, which are mediators of pain and inflammation.

Pharmacodynamics

Pharmacodynamics refers to the effects of the drug on the body, including the relationship between drug concentration and effect. It encompasses the drug's efficacy, potency, and therapeutic index. For example, a drug's efficacy is indicated by its ability to produce a desired effect, while potency refers to the amount of drug needed to produce that effect. Additionally, the therapeutic index is a measure of the safety of the drug, comparing the dose that produces toxicity to the dose that produces the desired therapeutic effect.

Pharmacokinetics

Pharmacokinetics involves the study of how the body absorbs, distributes, metabolizes, and excretes a drug. Key processes include absorption from the site of administration, distribution throughout the body's tissues, metabolism primarily by the liver, and excretion mainly via the kidneys. Factors such as bioavailability, volume of distribution, clearance rate, and half-life are crucial for understanding a drug's pharmacokinetics. Variability in these parameters can be influenced by age, sex, genetic factors, and the presence of other medications.

Pregnancy

Consult with a healthcare professional before use, as safety during pregnancy is not well established.

Breast-feeding

Consult with a healthcare professional before use, as it is not known if this drug passes into breast milk.

Storage

Store at room temperature, away from moisture and heat. Keep out of reach of children.

Indications

• Chronic fatigue syndrome
• Fibromyalgia
• Muscle fatigue
• Energy metabolism support

Dosage

Children: Refer to established clinical guidelines for specific dosing recommendations.

Adults: Refer to established clinical guidelines for specific dosing recommendations.

Mechanism of action

Malic acid enhances the availability of energy by participating in the Krebs cycle, where it contributes to the production of ATP (adenosine triphosphate), the energy currency of the cell. It may also facilitate the transport of nutrients across cell membranes and has been suggested to improve muscle function and reduce muscle fatigue through its role in mitochondrial energy production.

Pharmacodynamics

Malic acid is known to have a mild alkalizing effect, which may help reduce lactic acid buildup in muscles during exercise, thus potentially decreasing muscle soreness and improving endurance. Its antioxidant properties may also help in reducing oxidative stress, contributing to overall cellular health.

Pharmacokinetics

Malic acid is absorbed in the gastrointestinal tract after oral administration. It is distributed throughout the body, where it participates in various metabolic processes. The elimination half-life of malic acid is not well-defined, but it is primarily metabolized in the liver and excreted via urine as a result of its involvement in the Krebs cycle.

Adverse effects

• Nausea
• Diarrhea
• Abdominal discomfort
• Headache

Interactions

• May interact with certain medications that affect kidney function
• Potential interactions with medications metabolized by the liver

Precautions

• Use with caution in patients with renal impairment
• Consider potential interactions with other dietary supplements

Pregnancy

Insufficient data on the safety of malic acid during pregnancy. Consult healthcare providers before use.

Breast-feeding

Limited information available on the excretion of malic acid in human milk. Caution is advised if used during breastfeeding.

Storage

Store in a cool, dry place away from direct sunlight.

Formulations

• Oral tablets
• Powder for oral solution
• Capsules

Mechanism of action

Many of supplemental L-arginine's activities, including its possible anti-atherogenic actions, may be accounted for by its role as the precursor to nitric oxide or NO. NO is produced by all tissues of the body and plays very important roles in the cardiovascular system, immune system and nervous system. NO is formed from L-arginine via the enzyme nitric oxide synthase or synthetase (NOS), and the effects of NO are mainly mediated by 3,'5' -cyclic guanylate or cyclic GMP. NO activates the enzyme guanylate cyclase, which catalyzes the synthesis of cyclic GMP from guanosine triphosphate or GTP. Cyclic GMP is converted to guanylic acid via the enzyme cyclic GMP phosphodiesterase. NOS is a heme-containing enzyme with some sequences similar to cytochrome P-450 reductase. Several isoforms of NOS exist, two of which are constitutive and one of which is inducible by immunological stimuli. The constitutive NOS found in the vascular endothelium is designated eNOS and that present in the brain, spinal cord and peripheral nervous system is designated nNOS. The form of NOS induced by immunological or inflammatory stimuli is known as iNOS. iNOS may be expressed constitutively in select tissues such as lung epithelium. All the nitric oxide synthases use NADPH (reduced nicotinamide adenine dinucleotide phosphate) and oxygen (O2) as cosubstrates, as well as the cofactors FAD (flavin adenine dinucleotide), FMN (flavin mononucleotide), tetrahydrobiopterin and heme. Interestingly, ascorbic acid appears to enhance NOS activity by increasing intracellular tetrahydrobiopterin. eNOS and nNOS synthesize NO in response to an increased concentration of calcium ions or in some cases in response to calcium-independent stimuli, such as shear stress. In vitro studies of NOS indicate that the Km of the enzyme for L-arginine is in the micromolar range. The concentration of L-arginine in endothelial cells, as well as in other cells, and in plasma is in the millimolar range. What this means is that, under physiological conditions, NOS is saturated with its L-arginine substrate. In other words, L-arginine would not be expected to be rate-limiting for the enzyme, and it would not appear that supraphysiological levels of L-arginine which could occur with oral supplementation of the amino acid^would make any difference with regard to NO production. The reaction would appear to have reached its maximum level. However, in vivo studies have demonstrated that, under certain conditions, e.g. hypercholesterolemia, supplemental L-arginine could enhance endothelial-dependent vasodilation and NO production.

Pharmacodynamics

Studies have shown that is has improved immune responses to bacteria, viruses and tumor cells; promotes wound healing and regeneration of the liver; causes the release of growth hormones; considered crucial for optimal muscle growth and tissue repair.