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General Description:

Gadopiclenol, identified by CAS number 933983-75-6, is a notable compound with significant therapeutic applications. Gadopiclenol is a gadolinium-based contrast agent (GBCA) based on a pyclen macrocyclic structure. It is indicated for use with magnetic resonance imaging (MRI) to detect and visualize lesions with abnormal vascularity in the central nervous system and the body. In 2006, the use of GBCAs was associated with the development of nephrogenic systemic fibrosis (NSF), a rare disorder characterized by the thickening and hardening of skin and subcutaneous tissues. However, studies revealed that NSF was associated with linear GBCAs, not macrocyclic GBCAs, such as gadopiclenol. Gadopiclenol has high kinetic stability and a high r1 relaxivity, allowing it to be used at lower doses than classic extracellular GBCAs. In September 2022, the use of gadopiclenol was approved by the FDA. The product label includes a black box warning regarding the increased risk for NSF among patients with impaired elimination of the drugs.

Indications:

This drug is primarily indicated for: Gadopiclenol is indicated in adult and pediatric patients aged 2 years and older for use with magnetic resonance imaging (MRI) to detect and visualize lesions with abnormal vascularity in the central nervous system (brain, spine, and associated tissues) and the body (head and neck, thorax, abdomen, pelvis, and musculoskeletal system). Its use in specific medical scenarios underscores its importance in the therapeutic landscape.

Metabolism:

Gadopiclenol undergoes metabolic processing primarily in: Gadopiclenol is not metabolized and is eliminated unchanged. This metabolic pathway ensures efficient processing of the drug, helping to minimize potential toxicity and side effects.

Absorption:

The absorption characteristics of Gadopiclenol are crucial for its therapeutic efficacy: At a dose range between 0.025 mmol/kg and 0.3 mmol/kg (0.5 times to 6 times the recommended dosage), the C_max and AUC_inf of gadopiclenol increases in a dose-proportional manner. At the recommended dose, gadopiclenol has a C_max of 525 µg/mL and an AUC_inf of 569 µg·h/mL. A study that evaluated the pharmacokinetic parameters of gadopiclenol in healthy subjects and patients with brain lesions did not detect significant differences between the two groups. The drug's ability to rapidly penetrate into cells ensures quick onset of action.

Half-life:

The half-life of Gadopiclenol is an important consideration for its dosing schedule: Gadopiclenol has a mean elimination half-life of is 1.5 hours. This determines the duration of action and helps in formulating effective dosing regimens.

Protein Binding:

Gadopiclenol exhibits a strong affinity for binding with plasma proteins: At clinically relevant concentrations, the protein binding of gadopiclenol is ≤ 1.8%. This property plays a key role in the drug's pharmacokinetics and distribution within the body.

Route of Elimination:

The elimination of Gadopiclenol from the body primarily occurs through: Gadopiclenol is mainly excreted in urine by glomerular filtration. Within 48 hours after administration, approximately 98% of the gadopiclenol dose was recovered in urine. Understanding this pathway is essential for assessing potential drug accumulation and toxicity risks.

Volume of Distribution:

Gadopiclenol is distributed throughout the body with a volume of distribution of: At steady state, the mean volume of distribution of gadopiclenol is 13 L. This metric indicates how extensively the drug permeates into body tissues.

Clearance:

The clearance rate of Gadopiclenol is a critical factor in determining its safe and effective dosage: Gadopiclenol has a total body clearance of 100 mL/min and a renal clearance of 81 mL/min. It reflects the efficiency with which the drug is removed from the systemic circulation.

Pharmacodynamics:

Gadopiclenol exerts its therapeutic effects through: Variations in radiofrequency signal intensity allow the visualization of normal and pathological tissues during magnetic resonance imaging (MRI). These variations occur due to differences in proton density, differences of the spin-lattice or longitudinal relaxation times (T1), or differences in the spin-spin or transverse relaxation time (T2). Gadopiclenol shortens the T1 and T2 relaxation times and allows the visualization of targeted tissues during an MRI. The extent to which a contrast agent can affect the relaxation rate of tissue water (1/T1 or 1/T2) is termed relaxivity (r1 or r2). Gadopiclenol has a high r1 relaxivity compared to other gadolinium-based contrast agents. The use of gadopiclenol is not associated with QT interval prolongation; however, it can increase the risk for nephrogenic systemic fibrosis in patients with impaired elimination of the drugs. The use of gadopiclenol may also cause hypersensitivity reactions and acute kidney injury. The drug's ability to modulate various physiological processes underscores its efficacy in treating specific conditions.

Mechanism of Action:

Gadopiclenol functions by: Gadopiclenol is a macrocyclic non-ionic complex of gadolinium and a paramagnetic molecule that develops a magnetic moment when placed in a magnetic field. The magnetic moment alters the relaxation rates of water protons in its vicinity in the body. Its use in magnetic resonance imaging (MRI) allows to selectively increase contrast in tissues where gadopiclenol accumulates. This mechanism highlights the drug's role in inhibiting or promoting specific biological pathways, contributing to its therapeutic effects.

Toxicity:

Categories:

Gadopiclenol is categorized under the following therapeutic classes: Contrast Media, Diagnostic Uses of Chemicals, Gadolinium-based Contrast Agent, Lanthanoid Series Elements, Magnetic Resonance Contrast Activity, Magnetic Resonance Imaging Contrast Media, Paramagnetic Contrast Agent, Paramagnetic Contrast Media. These classifications highlight the drug's diverse therapeutic applications and its importance in treating various conditions.