Stability studies on admixtures of 5-fluorouracil with carboplatin and 5-fluorouracil with heparin for administration in continuous infusion regimens

Abstract

The therapeutic index of several anticancer agents may be improved by replacing rapid infusion/bolus injection schedules with prolonged continuous infusion regimens. Admixtures of 5-fluorouracil (5FU) with carboplatin and 5FU with heparin were subjected to stability studies to establish the feasibility of administering these infusions on an in-patient and out-patient basis, respectively. In the first study the stability of carboplatin was determined in an admixture of carboplatin and 5FU for neoadjuvant treatment of in-patients with oesophageal carcinoma by 5-day infusion. A previous study had reported significant carboplatin degradation in 5FU/carboplatin admixtures. Our results were consistent with this study and demonstrated that under ward conditions (25 degrees C) carboplatin also degraded (16% in 24 h) in dilute admixtures with 5FU. However, the addition of a citric acid buffer, which reduced infusion pH from 8.65 to 6.5, increased the stability of carboplatin (4.8% degradation in 24 h), without compromising 5FU solubility or stability. In a second study, the stability of an infusion containing 5FU and heparin was determined. Prolonged continuous infusion is routinely used for adjuvant treatment of colorectal carcinoma but episodes of thromboses and occlusion of the central venous catheter have been associated with this treatment.(ABSTRACT TRUNCATED AT 250 WORDS)