The Pharmacokinetics of the Conopeptide Contulakin-G (CGX-1160) After Intrathecal Administration: An Analysis of Data from Studies in Beagles

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BACKGROUND:The synthetic peptide agent Contulakin-G (CGX-1160), isolated from the toxin of the snail Conus Geographus, produces significant analgesia in animals. Its peptide structure requires intrathecal administration for effectiveness, therefore we determined the intrathecal pharmacokinetics of CGX-1160 after bolus dose and multiple day infusions to beagles.METHODS:For the bolus dose study, eight animals received a dose ranging from 16.7 to 1000 nmol under isoflurane anesthesia. Cerebral spinal fluid sampling for drug assay occurred up to 24 h. For the multiple day infusion study, three animals received infusions of 10, 40, and 160 μg/h respectively for 24 h at each rate. Cerebral spinal fluid sampling occurred during the infusion rate and the washout period after the 72 h of cumulative drug delivery. Data from the two study designs were modeled separately using NONMEM.RESULTS:The results showed a biexponential disposition profile for both experiments with a rapid rate constant that was an order of magnitude greater than the slow rate constant. The bolus results showed a nonlinear dependence of the slow rate constant on administered dose due to the large bolus range used in the study.CONCLUSION:These data, coupled with clinical pharmacology results, provide a basis for determining appropriate dosing strategies to achieve therapeutic intrathecal concentrations of Contulakin-G.

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