Direct cerebrospinal fluid delivery of an antiretroviral agent using multivesicular liposomes

Article Abstract:

It is generally understood that infection with human immunodeficiency virus (HIV, which causes AIDS) suppresses the immune system. However, HIV also infects the central nervous system (CNS). Therefore, drugs used to treat HIV infection must be able to penetrate cerebrospinal fluid (CSF, which protects the brain and spinal cord). Many antiviral agents, such as 2',3'-dideoxycytidine (DDC), do not readily cross the blood-brain barrier, which functions between the circulation and the brain to prevent certain substances from entering brain tissue and CSF. Direct injection of such drugs into the CSF has had limited success. In an attempt to improve drug delivery to the CNS, a method was developed to aid drug entry into the CSF. This procedure involves placing the drug inside of a small, circular, enclosed vesicle made from lipid cell membranes. The vesicle is designed to help the drug enter the CSF and be released slowly into the CNS. This procedure was tested in rats. DDC was encapsulated in a lipid vesicle and injected into the CSF of rats. The half-life (the time required for half of the drug to be metabolized) of encapsulated DDC in CSF was 23 hours, compared with a half-life of 1.1 hours for DDC that was injected directly into the CSF without a lipid vesicle capsule. These findings indicate that using lipid vesicles may provide a new method for administering drugs into CSF. (Consumer Summary produced by Reliance Medical Information, Inc.)

Drugs, HIV infection, Drug therapy, HIV infections, Drug delivery systems, Liposomes, Zalcitabine, Timed release drugs

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Instillation of vancomycin into a cerebrospinal fluid reservoir to clear infection: pharmacokinetic considerations

Article Abstract:

The development of the Ommaya reservoir, a surgically installed device by which drugs could be safely injected into the brain, allowed the direct introduction of medication beyond the blood-brain barrier. (The blood-brain barrier prevents certain harmful substances, and sometimes beneficial substances, in the blood from reaching brain tissue.) Unfortunately, reservoir-associated infections have been reported in some patients. Treatment difficulties have been attributed to the presence of antibiotic-resistant bacteria. The antibiotic vancomycin was used to treat a reservoir-associated infection in a 25-year-old man diagnosed with cancer. Because there were no available guidelines for injecting this antibiotic into the reservoir, an effective and safe dosage of vancomycin had to be determined. Clinicians relied on pharmacokinetics, the study of the action of drugs, with particular attention paid to the time required for absorption, duration of action, distribution in the body, and the method the body uses to excrete the drug. Their goal was to determine whether patient-specific dosing was possible. It was found that pharmacokinetics was useful to individualize dosing based on the patient's symptoms, rather than on standardized treatment guidelines, which may have resulted in vancomycin levels that were too low (ineffective) or too high (toxic). (Consumer Summary produced by Reliance Medical Information, Inc.)

Infection, Brain, Vancomycin, Pharmacokinetics

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