Chemical stability of an admixture combining ziconotide and bupivacaine during simulated intrathecal administration.

Objective. To determine the stability of an admixture combining ziconotide with bupivacaine hydrochloride during simulated intrathecal infusion under laboratory conditions at 37°. Materials and Methods. An admixture containing ziconotide (25 µg/mL) and bupivacaine hydrochloride (5 mg/mL) was stored in SynchroMed® II pumps at 37° and in control vials at either 37° or 5°. Using high-performance liquid chromatography, drug concentrations were determined from samples obtained at varying intervals during the 30-day study. Results. After 30 days, pump ziconotide and bupivacaine hydrochloride concentrations measured an average of 86.9% and 99.4% of their initial concentrations, respectively. Control vials displayed similar degradation rates for both drugs. Statistical evaluation of the ziconotide 95% confidence interval indicated that the ziconotide concentration would meet or exceed 90% and 80% of initial concentration for 22 days and 45 days, respectively. Conclusions. An admixture containing 25 µg/mL ziconotide and 5 mg/mL bupivacaine hydrochloride was 90% stable for 22 days and 80% stable for 45 days (extrapolated) in SynchroMed® II infusion pumps.

Chemical stability of admixtures combining ziconotide with baclofen during simulated intrathecal administration.

Objective. To determine the stability of admixtures combining ziconotide with commercially formulated or powdered baclofen during simulated intrathecal infusion under laboratory conditions at 37°. Materials and Methods. Admixtures of ziconotide (25 µg/mL) with commercially formulated (1.5 mg/mL) or powdered (2.0 mg/mL) baclofen were stored in implantable intrathecal pumps at 37°. Drug concentrations were determined with high-performance liquid chromatography, and the length of time that the concentrations of both drugs remained ≥90% and ≥80% of initial (ie, the 90% and 80% stability, respectively) was estimated based on lower 95% confidence bounds obtained via linear regression. Results. Baclofen was stable in both admixtures. In the commercially formulated baclofen admixture, the mean ziconotide concentration declined to 82.2% of initial in 30 days; the estimates for 90% and 80% stability were 12 and 29 days, respectively. In the powdered baclofen admixture, the mean ziconotide concentration declined to 87.4% of initial in 30 days; the estimates for 90% and 80% stability were 20 and 41 days, respectively. Conclusion. Ziconotide-baclofen admixtures were more stable when prepared using powdered baclofen rather than a commercial baclofen formulation.

Chemical stability of ziconotide-clonidine hydrochloride admixtures with and without morphine sulfate during simulated intrathecal administration.

Objective. To determine the stability of ziconotide-clonidine hydrochloride admixtures with and without morphine sulfate during simulated intrathecal infusion under laboratory conditions at 37°. Materials and Methods. Admixtures of ziconotide (25 µg/mL) and clonidine hydrochloride (2 mg/mL) with and without morphine sulfate (35 mg/mL) were stored in Medtronic SynchroMed® II pumps at 37°. Pumps were sampled immediately after filling and at four additional time points over the course of 28 (ziconotide-clonidine hydrochloride admixture) or 20 (ziconotide-clonidine hydrochloride-morphine sulfate admixture) days. Drug concentrations were determined using high-performance liquid chromatography. Results. Ziconotide concentration exceeded 97% of initial at all time points when combined with clonidine alone; statistical evaluation indicated that both ziconotide and clonidine concentrations would remain above 90% of initial for more than 60 days. When compounded with both clonidine and morphine, ziconotide and clonidine concentrations declined; statistical evaluation indicated that the ziconotide concentration was 70% of initial after 20 days, and that clonidine would remain 90% stable for 42 days. Morphine was stable in the presence of ziconotide and clonidine. Conclusions. A ziconotide-clonidine admixture was 90% stable for 60 days (extrapolated), and a ziconotide-clonidine-morphine admixture was 70% stable for 20 days.

Chemical Stability of Admixtures Combining Ziconotide with Morphine or Hydromorphone During Simul ated Intrathecal Administration.

Objective. To determine the stability of admixtures combining ziconotide with morphine or hydromorphone under simulated intrathecal infusions. Materials and Methods. Admixtures of ziconotide (25 µg/mL) with morphine or hydromorphone (both at 35 mg/mL) were stored in Medtronic SynchroMed® II pumps at 37°C, and in control vials at 37°C and 5°C. Drug concentrations were determined using high-performance liquid chromatography. Results. The ziconotide pump concentration with morphine declined to 79% of initial in 17 days, and to 88% of initial after 25 days with hydromorphone. Ziconotide concentrations in control vials stored at 37°C displayed similar rates of decay, but vials stored at 5°C exhibited no ziconotide loss. A statistical evaluation of the two combinations shows ziconotide-hydromorphone retaining 80% stability for 40 days (extrapolated), compared to 15 days for ziconotide-morphine. Morphine and hydromorphone were stable in the presence of ziconotide under all conditions. Conclusions. Ziconotide-hydromorphone admixtures were more stable than ziconotide-morphine admixtures.