roquinimex

Action and Spectrum

Actions and Spectrum: 

Actions: 

Roquinimex, also known as Linomide, belongs to the category of quinoline-derivative immunostimulants. It enhances NK cell activity and macrophage cytotoxicity while concurrently inhibiting angiogenesis and diminishing the secretion of TNF-alpha. 

It has been under scrutiny as a potential treatment for various conditions, including certain cancers. This includes its exploration following bone marrow transplantation as adjuvant therapy in cases of acute leukemia. Additionally, Roquinimex has been investigated for its potential application in autoimmune diseases such as multiple sclerosis and recent-onset type I diabetes. 

Spectrum: 

Linomide, LS 2616, and roquinimex are quinoline-3-carboxamides that are well-known for their broad spectrum of immune-modulating properties. These compounds have shown therapeutic efficacy in a variety of experimental animal models of autoimmune disorders. Clinical experiments on limozide specifically for multiple sclerosis revealed significant results that inhibited the disease. Unfortunately, these clinical trials had to end early due to unanticipated adverse effects detected in treated patients.

The mechanism(s) Linomide uses to improve autoimmune disorders still needs to be determined. According to specific experimental findings, linomide may regulate cytokine profiles, which in turn suppresses inflammatory and autoimmune diseases. 

Furthermore, by preventing endothelial cell migration, proliferation, and basement membrane invasion, roquinimex may have anti-cancer effects. It inhibits angiogenesis and reduces tumor-associated macrophages (TAMs) release of the angiogenic factor tumor necrosis factor-alpha. Roquinimex proceeded to phase III clinical studies with Pharmacia Corporation, which were carried out in the US and Europe with the goal of determining how well it worked as a treatment for multiple sclerosis.

Drug Interaction

Adverse Reaction

Frequency not defined 

Nausea 

Musculoskeletal discomfort 

Pain 

Cardiovascular toxicity

Black Box Warning

N/A

Contraindication / Caution

Contraindication/Caution: 

Contraindications 

• Hypersensitivity 

Cautions 

• Renal impairment 
• Hepatic impairment 
• Drug interactions 
• Pregnancy  
• Breastfeeding

Pregnancy / Lactation

Pregnancy consideration:  

No data is available regarding the administration of the drug during pregnancy. 

Breastfeeding warnings:  

No data is available regarding the excretion of drug in breast milk. 

Pregnancy category: 

Category A: well-controlled and satisfactory studies show no risk to the fetus in the first or later trimester. 

Category B: there was no evidence of risk to the fetus in animal studies, and there were not enough studies on pregnant women. 

Category C: there was evidence of risk of adverse effects in animal reproduction studies, and no adequate evidence in human studies must take care of potential risks in pregnant women.    

Category D: adequate data with sufficient evidence of human fetal risk from various platforms, but despite the potential risk, and used only in emergency cases for potential benefits.    

Category X: Drugs listed in this category outweigh the risks over benefits. Hence these categories of drugs need to be avoided by pregnant women.    

Category N: No data is available for the drug under this category. 

Pharmacology

Pharmacology: 

Quinoline is the source of the immunostimulant roquinimex, commonly referred to as linomide. In addition to promoting macrophage cytotoxicity and NK cell function, it suppresses angiogenesis and lowers TNF-alpha release. 

Pharmacodynamics: 

Roquinimex (Linomide) has demonstrated its capacity to impede tumor growth in animal models, a phenomenon linked, at least in part, to the heightened numbers and activity of natural killer (NK) cells. In a clinical pilot study encompassing 13 patients with various malignant disorders and performance status ranging from 0 to 3, escalating doses of roquinimex (ranging from 0.05 mg/kg to 0.6 mg/kg) were administered. Throughout the study, parameters related to immunology were closely monitored, and side effects were meticulously documented. At the 0.2 mg/kg dose level, an exploration of plasma pharmacokinetics was undertaken.

Clinical side effects predominantly presented as musculoskeletal discomfort, nausea, and pain, with no discernible hematological or biochemical toxicity. A pharmacokinetic analysis at the 0.2 mg/kg dose level unveiled a Cmax of 4.0 mumol/L at tmax of 1.2 hr and an elimination half-life of 42 hr. Notably, the administration of roquinimex led to increased numbers of phenotypic NK cells, activated T (DR+CD4+) cells, and monocytes compared to baseline values. This suggests that Roquinimex functions as an active immunomodulator with manageable toxicity, prompting consideration for further exploration of its therapeutic efficacy. 

Pharmacokinetics: 

Absorption 

The bioavailability is 99% 

Distribution 

The volume of distribution is 0.21 L/kg 

Metabolism 

N/A 

Elimination and Excretion 

The half-life is 31 hours 

Adminstartion

Administration: 

Roquinimex is administered orally one time a day. If tolerated at a minimum dose, it is escalated to higher doses by monitoring side effects.

Patient Information Leaflet

Patient information leaflet 

Generic Name: roquinimex 

Pronounced: roh-kwuh-ni-meks 

Why do we use roquinimex? 

Roquinimex (Linomide) is a synthetic immunomodulator that has demonstrated effectiveness in animal models of diverse autoimmune diseases. Its principal actions are believed to occur through the suppression of interferon-gamma (IFN-γ) and tumor necrosis factor-alpha (TNF-α) release from natural killer (NK) cells and the modulation of macrophage activity.