Published in:
01-07-2009 | Original Article
Plasma and cerebrospinal fluid pharmacokinetics of tasidotin (ILX-651) and its metabolites in non-human primates
Published in: Cancer Chemotherapy and Pharmacology | Issue 2/2009
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Purpose
To evaluate the plasma and cerebrospinal fluid (CSF) pharmacokinetics and CSF penetration of tasidotin and metabolites in a nonhuman primate model.
Methods
Tasidotin 0.75 mg/kg was administered intravenously. The plasma and CSF concentrations of tasidotin and its metabolites were determined. Pharmacokinetic parameters were estimated using model-independent and model-dependent methods.
Results
The mean (±SD) CSF:plasma AUC ratio for tasidotin was 1.1 ± 0.4. For tasidotin, tasidotin-C-carboxylate and desprolyl-tasidotin-C-carboxylate the plasma AUCs (mean ± SD) were 30 ± 10, 54 ± 19 and 12 ± 2 μM min, and apparent plasma half-lives were 27 ± 4, 229 ± 73 and 100 ± 29 min. The plasma clearance of tasidotin was 44 ± 14 ml/min/kg. The CSF AUC and half-life of tasidotin was 28 ± 10 μM min and 96 ± 40 min. The model-dependent plasma clearance was 35 ml/min/kg for tasidotin and 2 ml/min/kg for tasidotin-C-carboxylate.
Conclusions
Tasidotin penetrates into the CSF well and further evaluation of its activity in the treatment of central nervous system malignancies should be considered.