Compatibility and Stability of the Investigational Polypeptide Marine Anticancer Agent Kahalalide F in Infusion Devices
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Kahalalide F is a novel marine-derivedantitumor agent isolated from the marinemollusk Elysia rufescens, an organismliving in the seas near Hawaii. Thecompound has shown highly selective invitro activity against prostate tumors andphase I trials in patients with androgenindependent prostate tumors incorporating adaily times five and weekly schedule have been initiated.Kahalalide F is pharmaceuticallyformulated as a lyophilized productcontaining 150 μg active substance perdosage unit. Prior to i.v. administrationit is reconstituted with a solutioncomposed of Cremophor EL, ethanol absoluteand Water for Injection (CEW, 5/5/90%v/v/v) with further dilution in 0.9% w/vsodium chloride for infusion. The aim ofthis study was to investigate thecompatibility and stability of kahalalide Fwith different infusion systems prior tothe start of clinical trials with thecompound. Due to the presence of CremophorEL in the infusion solution, leaching ofdiethylhexyl phthalate (DEHP) from polyvinylchloride infusion containers (PVC,Add-a-Flex®) was found. Loss ofkahalalide F as a consequence of sorptionto contact surfaces was shown with aninfusion container composed of low densitypolyethylene (LD-PE, Miniflac®). Weconclude that kahalalide F must beadministered in a 3-h infusion inconcentrations of 0.5 μg/mL to14.7 μg/mL using an administration setconsisting of a glass container anda low-extrables, DEHP-free extension set.Kahalalide F 150 μg/vial powder for infusionreconstituted with 5/5/90% v/v/v CEW isstable in the original container for atleast 24 h at room temperature(+20–25 °C) and ambient lightconditions. Infusion solutions stored inglass infusion containers at either roomtemperature (+20–25 °C, in the dark)or refrigerated conditions (+2–8 °C,in the dark) are stable for at least 5 daysafter preparation.
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- 1.Jimeno JM, Faircloth JM, Cameron L, Meely K, Vega E, Gómez A, Sousa-Faro JMF, Rinehart K: Progress in the acquisition of new marine-derived anticancer compounds: development of ecteinascidin-743 (ET-743). Drugs of the Future 21: 1155–1165, 1996Google Scholar
- 2.Supko JG, Lu H: Preclinical pharmacology studies with the marine natural product kahalalide F. Clin Cancer Res 5: 3792s, 1999Google Scholar
- 3.Faircloth G, Grant W, Smith B, Supko J, Brown A, Geldof A, Jimeno J: Preclinical development of kahalalide F, a new marine compound selected for clinical studies. Proc Am Ass Cancer Res 41: 600, 2000Google Scholar
- 4.Trissel LA, Xu Q, Kwan J, Martinez JF: Compatibility of paclitaxel injection vehicle with intravenous administration and extension sets. Am J Hosp Pharm 51: 2804–2810, 1994Google Scholar
- 5.Nuijen B, Bouma M, Henrar REC, Manada C, Bult A, Beijnen JH: Compatibility and stability of aplidine, a novel marinederived depsipeptide antitumor agent, in infusion devices, and its hemolytic and precipitation potential upon i.v. administration. Anti-cancer Drugs: 10: 879–887, 1999Google Scholar
- 6.Sautou-Miranda V, Brigas F, Vanheerswynghels S, Chopineau J: Compatibility of paclitaxel in 5% glucose solution with ECOFLAC® low-density polyethylene containers-stability under different storage conditions. Int J Pharm 178: 77–82, 1999Google Scholar
- 7.Cheung AP, Hallock YF, Vishnuvajjala BR, Nguyenle T, Wang E: Compatibility and stability of bryostatin 1 in infusion devices. Inv New Drugs 16: 227–236, 1999Google Scholar
- 8.Trissel LA: Pharmaceutical properties of paclitaxel and their effects on preparation and administration. Pharmacotherapy 17: 133s–139s, 1997Google Scholar
- 9.Mazzo DJ, Nguyen-Huu JJ, Pagniez S, Denis P: Compatibility of docetaxel and paclitaxel in intravenous solutions with polyvinyl chloride infusion materials. Am J Health-Syst Pharmac 54: 566–569, 1997Google Scholar
- 10.Maas B, Huber C, Krämer I: Plasticizer extraction of Taxol® infusion solution from various infusion devices. Pharmac World Sc 18: 78–82, 1996Google Scholar
- 11.Sloof W, Janus JA, Koning CJM, Peijnenburg WJGM, Ros JPM: Exploratory report phthalates. Report no. 710401001. Bilthoven: Rijksinstituut voor Volksgezondheid en Milieuhygiene (RIVM) 1990Google Scholar