Singapore Drugs Database

Indication

Bicisate as a complex with technetium Tc-99m is used in single photon emission computerized tomography (SPECT) as an adjunct to conventional CT or MRI in the localization of stroke in patients whom the presence of a stroke has already been diagnosed. It is not indicated to assess the functional viability of brain tissue or to distinguish between a stroke and other brain lesions.[L2034] A stroke is defined as a condition in which the blood stops flowing to any part of the brain causing a damage to brain cells. The potential effect of a stroke depends on the part of the brain that was affected by it as well as the extension of the damage.[L2069]

Mechanism of Action

Bicisate is rapidly uptaken by the brain. The retention of bicisate in the brain is associated with stereospecific de-esterification to hydrophilic acid derivatives.[A32374] Even though both DD and LL isomers demonstrate brain uptake, only the LL presents brain retention.[T153] Bicisate brain localization is performed by passive diffusion and the presence of slow hydrolysis in the blood and rapid hydrolysis in the brain. The hydrolysis of bicisate forms the monoacid and diacid bicisate derivatives. The formation of these derivatives results in high brain uptake and retention.[T152, T153] The uptake of bicisate depends on the blood flow directed to the brain and thus the presence of a stroke will be translated into specific zones in the brain that would not include the complex of bicisate and technetium Tc-99m.

Pharmacokinetics

Absorption

After intravenous administration, bicisate presents a very large brain extraction.[A32374] About 5% of the administered dose remains in the blood one hour after administration. The highest concentration of radioactivity in blood was attained 0.5 minutes after intravenous injection and it represented 13.9% of the injected dose.[L2034] After intravenous administration of bicisate, the permeability surface area was 0.48 ml.g/min.[A32395]

Distribution

After intravenous administration of bicisate, the distribution volume was 0.74 L.[A32395]

Metabolism

Bicisate is metabolized to form mono- and di-acids by the action of esterases. The exact metabolic transformation has not been elucidated.[L2034, T154]

Elimination

Clearance

The clearance of bicisate from 1 to 24 hours, studied as a loss of hydrophilic tracer, is of approximate 3.5% per hour.[A32390]

Toxicity

In vitro, the complex of bicisate and technetium Tc-99m has been shown to cause unscheduled DNA synthesis and caused an increased frequency of chromatid exchange. Bicisate as a unique compound increased the apparent rate of gene mutation but it did not demonstrate clastogenic activity. Studies related to clastogenic potential or effects in fertility have not been performed.[L2034]

Active Ingredient/Synonyms

Bicisate | Bicisate |