Cytosine arabinoside (ara-C) is a component of many protocols for the treatment of CNS (central nervous system) leukemia and lymphoma in humans and dogs. It is also used for the prophylaxis of CNS metastasis in acute lymphoblastic leukemia. Although ara-C enters the cerebrospinal fluid (CSF) of human cancer patients after i.v. administration, it is unclear whether a similar CNS distribution occurs in humans whose blood-brain barrier has not been compromised by invasive disease. No information on the penetration of ara-C into the CSF in dogs is available. We studied the plasma and CSF pharmacokinetics of 600 mg/m2 ara-C in ten healthy male dogs after its administration as a rapid i.v. bolus (six dogs) or as a 12-h i.v. infusion (four dogs). Ara-C concentration in blood and CSF samples was determined by high-performance liquid chromatography (HPLC). After an i.v. bolus of ara-C, the mean plasma distribution half-life was 7.1 +/- 4.5 min and the mean elimination half-life was 69 +/- 28 min. The mean plasma clearance was 227 +/- 125 ml min-1 m-2. The peak concentration of ara-C in the CSF was 29 +/- 11 microM, which occurred at 57 +/- 13 min after the ara-C bolus. The CSF elimination half-life was 113 +/- 26 min. During a 12-h infusion of ara-C (50 mg m-2 h-1), the plasma steady-state concentration was 14.1 +/- 4.2 microM, the CSF steady-state concentration was 8.3 +/- 1.1 microM, and the CSF: plasma ratio was 0.62 +/- 0.14. The plasma elimination half-life was 64 +/- 19 min and the plasma clearance was 214 +/- 69 ml min-1 m-2. The CSF elimination half-life was 165 +/- 28 min. No clinically significant toxicity was observed over a 21-day period following drug administration in either of the treatment groups. Our data indicate that ara-C crosses the blood-brain barrier in normal dogs and that i.v. administration of this drug has potential as a treatment modality for neoplasia involving the CNS.

It is hoped that we have demonstrated that collection, handling, and limited analysis of CSF samples from the dog and cat are relatively simple. No special equipment or handling is required, and the procedures are within the capabilities of any veterinarian interested in performing them. In addition, although this article was not intended to present a detailed discussion on the interpretation of the analysis of CSF, we have demonstrated some very practical interpretations to the various aspects of a routine CSF analysis. When combined with a signalment, complete history, and thorough general physical and neurologic examination, CSF analysis can prove invaluable in the workup of an animal with a neurologic disorder. Relatively simple laboratory procedures can be helpful in differentiating peripheral blood contamination from true intrathecal hemorrhage, in identifying an active inflammatory process, in potentially characterizing an etiologic agent, and, on rare occasions, in identifying primary or metastatic neoplastic disease involving the CNS. In many cases, the above is not directly possible, because the changes observed in our routine analysis are nonspecific. Yet, documenting and following these "nonspecific" alterations are helpful in determining if there is progression or regression of the disease process. In turn, these changes or lack of changes are helpful in identifying if the proper therapy has been instituted and if additional or different therapy is required.

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