Intracerebroventricular Administration of Drugs

Abstract

Intracerebroventricular drug administration is a method that bypasses the blood-brain barrier and other mechanisms that limit drug distribution into the brain, allowing high drug concentrations to enter the central compartment. Instillation of drugs directly into the ventricles of the brain must be done carefully and with full consideration of factors affecting the efficacy and safety of this route of administration. These factors include the osmolarity, pH, volume, and presence of preservatives and diluents of the drug solution being administered. Very few studies have formally investigated intraventricular therapies, and dosing recommendations may vary widely depending on the agent and the patient. Many antimicrobials have been given intraventricularly, although very few prospective studies have evaluated this strategy. There are wide variations among the reports regarding dosage regimens and the pharmacokinetics of the antimicrobials used. Guidance on appropriate formulations and their use is lacking. Clinicians should be aware of their patients' ongoing disease processes and neurologic status, as well as pertinent physiochemical properties of drugs when formulating them for intracerebroventricular administration; a high index of suspicion should be maintained when monitoring patients for adverse drug events after instillation.

Whole body correction of mucopolysaccharidosis IIIA by intracerebrospinal fluid gene therapy

“…Global CNS gene delivery following intrathecal AAV administration has been documented in cynomolgus macaques, a nonhuman primate species of small size (~3-7 kg), using self-complementary AAV vectors diluted in a hyperosmotic buffer (64); while the study provides evidence that the approach is potentially feasible, detailed confirmatory studies in larger animal models are needed. In humans, a comparison of aminoglycoside therapies after CSF administration indicates that lumbar delivery results in high aminoglycoside concentration in lumbar CSF, but rather low concentrations in ventricular CSF, whereas instillation in the lateral ventricles results in high ventricular and lumbar CSF concentrations (65). The results of these studies confirm the concept of unidirectional flow of CSF and suggest that i.c.v.…”

“…The results of these studies confirm the concept of unidirectional flow of CSF and suggest that i.c.v. administration of products may result in the most widespread distribution of drugs within CSF-containing compartments (63,65).…”

Pharmacokinetics of Colistin in Cerebrospinal Fluid after Intraventricular Administration of Colistin Methanesulfonate

“…Blank human CSF (250 l) was spiked with CMS at concentrations of 10, 20, 50, 100, and 200 g/ml and kept at 37°C. Assuming that the total volume of CSF in adult humans is 150 ml (5,23), the daily dose of CMS administered IVT to our patients was within this range. At 0.5, 1, 2, 4, 8, and 16 h, samples (250 l) were removed and analyzed immediately.…”

A2A adenosine receptor modulates drug efflux transporter P-glycoprotein at the blood-brain barrier

“…Many available drugs with the potential to treat these diseases are not effectively delivered to the brain due to the physical hindrance and efflux transporters imposed by the BBB. There have been numerous attempts to overcome the hindrance of drug delivery by the BBB that include physical disruption of the BBB, drug modification for easier passage across the BBB, and intrathecal injection of drugs into the brain (7)(8)(9)(10). However, these approaches have suffered from shortcomings, including toxicity, decreased drug efficacy, and invasiveness, that can result in permanent brain damage.…”