Paliperidone palmitate
[CAS# 199739-10-1]

Identification

• Classification: API >> Nervous system medication
• Name: Paliperidone palmitate
• Synonyms: 9-Hydroxyrisperidone palmitate; Hexadecanoic acid 3-[2-[4-(6-fluoro-1,2-benzisoxazol-3-yl)-1-piperidinyl]ethyl]-6,7,8,9-tetrahydro-2-methyl-4-oxo-4H-pyrido[1,2-a]pyrimidin-9-yl ester
• Molecular Formula: C₃₉H₅₇FN₄O₄
• Molecular Weight: 664.89
• CAS Registry Number: 199739-10-1
• EC Number: 682-873-3
• SMILES: CCCCCCCCCCCCCCCC(=O)OC1CCCN2C1=NC(=C(C2=O)CCN3CCC(CC3)C4=NOC5=C4C=CC(=C5)F)C

Properties

• Density: 1.19±0.1 g/cm³, Calc.^*
• Index of Refraction: 1.590, Calc.^*
• Boiling Point: 736.3±70.0 °C (760 mmHg), Calc.^*
• Flash Point: 399.1±35.7 °C, Calc.^*

^* Calculated using Advanced Chemistry Development (ACD/Labs) Software.

Safety Data

• Hazard Symbols: GHS06;GHS08 Danger
• Risk Statements: H301-H361-H362
• Safety Statements: P203-P260-P263-P264-P270-P280-P301+P316-P318-P321-P330-P405-P501

Hazard Classification

Hazard	Class	Category Code	Hazard Statement
Acute toxicity	Acute Tox.	3	H301
Reproductive toxicity	Lact.	-	H362
Reproductive toxicity	Repr.	2	H361
Chronic hazardous to the aquatic environment	Aquatic Chronic	2	H411
Specific target organ toxicity - repeated exposure	STOT RE	1	H372
Specific target organ toxicity - single exposure	STOT SE	3	H336

Discovery and Applications

Paliperidone palmitate is a long-acting injectable formulation of paliperidone, an atypical antipsychotic used in the treatment of schizophrenia and schizoaffective disorder. It is a prodrug, meaning that it is metabolized into the active form of paliperidone in the body. Paliperidone itself is the active metabolite of risperidone, another widely used antipsychotic. The development of paliperidone palmitate aimed to provide a more convenient and effective treatment option for patients with schizophrenia, reducing the need for daily oral medication and improving adherence to treatment.

The discovery and development of paliperidone palmitate followed extensive research into the limitations of oral antipsychotic medications, particularly issues related to patient non-adherence. Non-adherence is a significant problem in the management of schizophrenia, often leading to relapse and hospitalization. The goal was to create a medication that would be effective in maintaining therapeutic drug levels over an extended period, thus improving patient outcomes. Paliperidone palmitate was developed by Janssen Pharmaceuticals and first approved by the U.S. Food and Drug Administration (FDA) in 2009 for the treatment of schizophrenia.

Paliperidone palmitate is administered as an intramuscular injection, typically once a month or every three months, depending on the patient's needs. This long-acting formulation helps to maintain consistent drug levels in the body, reducing the fluctuations that can occur with oral medications. As a result, it helps to prevent relapse and improve the overall management of schizophrenia. The prolonged release of paliperidone from the palmitate ester form allows for a steady effect over time, providing a more stable treatment regimen for patients.

One of the key benefits of paliperidone palmitate is its ability to improve medication adherence in patients with schizophrenia. Many patients with schizophrenia face difficulties with daily medication regimens due to forgetfulness, stigma, or side effects. By offering a long-acting injectable option, paliperidone palmitate reduces the frequency of dosing, making it easier for patients to stick to their treatment plans. This, in turn, leads to better clinical outcomes, including a reduction in relapse rates and improvements in the overall quality of life for patients.

Paliperidone palmitate has been found to be effective in managing the positive and negative symptoms of schizophrenia. The positive symptoms, such as hallucinations and delusions, are typically more pronounced in the acute phase of the illness, while the negative symptoms, including social withdrawal and reduced emotional expression, can persist throughout the course of the disorder. Paliperidone palmitate has shown to be effective in both controlling these symptoms and preventing relapse, thus stabilizing the condition of patients with schizophrenia over time.

In addition to its use in schizophrenia, paliperidone palmitate has also been approved for the treatment of schizoaffective disorder, a condition characterized by both mood symptoms and psychosis. It is important to note that paliperidone palmitate should be used as part of a comprehensive treatment plan that includes psychotherapy and support for patients and their families.

The safety profile of paliperidone palmitate is generally favorable, with most side effects being similar to those of other atypical antipsychotics. Common side effects include weight gain, drowsiness, and injection site reactions. However, compared to other long-acting injectable antipsychotics, paliperidone palmitate has been associated with a lower risk of certain adverse effects, such as movement disorders, making it a preferable choice for many patients.

In conclusion, paliperidone palmitate represents a significant advancement in the treatment of schizophrenia and schizoaffective disorder. Its long-acting formulation allows for improved adherence to treatment, leading to better long-term outcomes for patients. With its proven efficacy and favorable safety profile, paliperidone palmitate is an important option in the management of these complex and chronic psychiatric conditions.

References

2024. Novel long-acting treatment for schizophrenia based on paliperidone dissolving and implantable microarray patches. European Journal of Pharmaceutics and Biopharmaceutics, 204. DOI: 10.1016/j.ejpb.2024.114481

2024. The development of paliperidone nanocrystals for the treatment of schizophrenia. Progress in Biomedical Engineering, 6(4). DOI: 10.1088/2516-1091/ad8fe7

2024. Model-Informed Clinical Development of 6-Monthly Injection of Paliperidone Palmitate in Patients with Schizophrenia: Dosing Strategies Guided by Population Pharmacokinetic Modeling and Simulation (Part II). European Journal of Drug Metabolism and Pharmacokinetics, 49(4). DOI: 10.1007/s13318-024-00899-z