Intraventricular Route

With increased meningeal inflammation, there will be greater antibiotic penetration (Table 36-3). Problems ofCSF penetration maybe overcome by direct instillation of antibiotics by intrathecal, intracisternal, or intraventricular routes of administration (Table 36-4). 

The use of intrathecal amphotericin B is not recommended for the treatment of cryptococcal meningitis except in very ill patients or in those with recurrent or progressive disease despite aggressive IV amphotericin B therapy. The dosage of amphotericin B employed is usually 0.5 mg administered via the lumbar, cisternal, or intraventricular (via an Ommaya reservoir) route two or three times weekly. 

Only the first three are discussed in any detail here. Most of these routes of administration place a drug directly or indirectly into systemic circulation. There are a number of these routes, however, by which the drug exerts a local effect, in which case most of the drug does not enter systemic circulation (e.g., intrathecal, intraventricular, intraocular, intraracistemal). Certain routes of administration may exert both local and systemic effects depending on the characteristics of the drug and excipients (e.g., subcutaneous). 

Other routes of administration can be employed in certain situations. Methotrexate and cytarabine are given intrathecally or intraventricularly to prevent relapses in the meninges in acute lymphocytic leukemia and to treat carcinomatous meningitis. Thiotepa and bleomycin have been administered by intravesical instillation to treat early bladder cancers. Fluorouracil can be applied topically for certain skin cancers. 

The formation of 0-methylated metabolites of THP, and of berbine 124, with rat liver microsomal enzymes was investigated in some detail 212,213). It was shown by Davis and colleagues that intraventricular application of racemic and optically active THP and of berbine 124 led after 1 hr to the formation of metabolites which were identified and quantitated by GC-MS methods. The results are summarized in Fig. 30. It can be seen that O-methylation of the hydroxy group at C-6 in both enantiomers of THP and the racemate necessary to connect with norreticuline (121) only was a minor pathway, and that O-methylation of the hydroxy group at C-7 was the preferred route. 0-MethyIation of the hydroxy group at C-11 in berbine 124 was preferred over that at C-10, as was the O-methylation of the hydroxy group at C-2 over that at C-3. 

Groothuis DR, Benalcazar H, Allen CV, Wise RM, Dills C, Dobrescu C, Rothholtz V, Levy RM. Comparison of cytosine arabinoside delivery to rat brain by intravenous, intrathecal, intraventricular and intra-parenchymal routes of administration. Brain Res 2000 856 281-90. 

Other routes of administration have been evaluated, such as inhalation, intrale-sional, intranasal, intraperitoneal, intraventricular, and intraocular rates, in clinical studies. For the most part, these alternative routes were attempts to improve the delivery of interferon to sites not easily accessible via the systemic circulation. These dosing strategies have provided adequate concentrations of interferon in cerebrospinal fluid, lymph, nasal mucosa, and peritoneal fluid, but have not led to clinical success, undoubtedly reflecting the lack of understanding of the inherent mechanism of interferon action [164]. 

Ease of use morphine and all the other injectable opioids are very easy to use. One major advantage of morphine that leads to its ease of use is the multiple routes of administration (IV, IM, SQ, IT epidural, intraventricular, rectal, oral, and inhalational). Morphine can easily be titrated to sedation levels, pain scores, and respiratory rate. 

In general, thymidine analogs can be administered via different routes, firom the less invasive (ingestion via drinking water, i.e., peroral (p.o.)) to the most invasive (direct intracerebroventricular or intraventricular (i.c.v.) injections). Of course, the most invasive routes are not the advisable ones for repeated administration. Most commonly, the thymidine analogs are administered intraperitoneally... 

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