Variability of mitomycin C adsorption by activated charcoal.
A saline suspension of mitomycin C adsorbed on activated charcoal and administered intraperitoneally has been reported to be safe and effective in the treatment of gastric carcinoma. Activated charcoal specifically targets tumour and lymph-node tissues and the sustained higher local drug concentration is thought to be beneficial. The charcoal particles used in these suspensions have varied in size from > 147 microm to < 20 nm in diameter, but no data have been published to show how this might affect drug adsorption and delivery. Any variability in drug adsorption could pose a serious clinical risk for drugs with a narrow therapeutic index. We have, therefore, investigated the adsorption of mitomycin C on activated charcoal in-vitro. Activated charcoal was ground and sieved to yield four size-fractions between 180 and 53 microm. Adsorption isotherms (n > or = 3) were constructed and applied to the Freundlich model with 0-l00 microg mL(-1) mitomycin C measured by HPLC with detection at 365 nm. Adsorption of mitomycin C by activated charcoal varied by a factor of three under identical conditions at room temperature (21 degrees C) and at 37 degrees C. The specific adsorption (microg mitomycin C (mg activated charcoal)(-1)) was generally higher at 37 degrees C than at room temperature. The variability of mitomycin C adsorption was greatly reduced by addition of the surface-active agent polyvinylpyrollidone, used to determine that adsorption of mitomycin C was independent of activated charcoal particle size. The characteristics of adsorption of mitomycin C by activated charcoal are complex and should be thoroughly investigated to discover the critical controlling factors before submitting the suspensions for further clinical evaluation.
Shah
I A
IA
Department of Pharmacology and Therapeutics, University of Liverpool, UK.
Lindup
W E
WE
McCulloch
P G
PG
D000327:Adsorption; D000903:Antibiotics, Antineoplastic / Q000032:analysis / Q000737:chemistry*; D002606:Charcoal / Q000737:chemistry*; D003692:Delayed-Action Preparations; D016503:Drug Delivery Systems; D016685:Mitomycin / Q000032:analysis / Q000737:chemistry*; D010316:Particle Size; D011205:Povidone / Q000737:chemistry; D015203:Reproducibility of Results; D013499:Surface Properties; D013535:Suspensions; D013696:Temperature
D000903:Antibiotics, Antineoplastic; D003692:Delayed-Action Preparations; D013535:Suspensions; D002606:Charcoal; D016685:Mitomycin; D011205:Povidone