PT  - JOURNAL ARTICLE
AU  - Nuijen, Bastiaan
AU  - Bouma, Marjan
AU  - Manada, Consuelo
AU  - Jimeno, José M.
AU  - Bult, Aune
AU  - Beijnen, Jos H.
TI  - <em>In Vitro</em> Hemolysis and Buffer Capacity Studies With the Novel Marine Anticancer Agent Kahalalide F and Its Reconstitution Vehicle Cremophor EL/Ethanol
DP  - 2001 Jul 01
TA  - PDA Journal of Pharmaceutical Science and Technology
PG  - 223--229
VI  - 55
IP  - 4
4099  - http://journal.pda.org/content/55/4/223.short
4100  - http://journal.pda.org/content/55/4/223.full
SO  - PDA J Pharm Sci Technol2001 Jul 01; 55
AB  - An in vitro biocompatibility study was performed with the pharmaceutical formulation of the investigational, marine-derived anticancer agent kahalalide F developed for early clinical studies. The pharmaceutical formulation consists of a lyophilized product containing 150 μg kahalalide F, 3 mg citric acid, 3 mg polysorbate 80, and 150 mg of sucrose per dosage unit, to be reconstituted with 3 mL of a mixture composed of Cremophor EL, ethanol, and water (5/5/90% v/v/v), resulting in a solution of pH 3 and to be further diluted in normal saline for infusion. The reconstituted product, infusion solutions, and Cremophor/ethanol (CE) vehicle were tested for hemolytic potential and buffer capacity. No significant hemolysis due to the kahalalide F formulation as well as the CE vehicle was found using both a static and dynamic test model. FB-ratio's (ratio of formulation solution (F) and volume of blood simulant (B) necessary to maintain physiological pH) as a measure of the buffer capacity of the kahalalide F infusion solutions examined indicated that no vascular irritation due to pH effects is expected in the intended administration schedule in the forthcoming Phase I study.