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PHARMACOKINETICS AND METABOLISM OF ANTIPYRINE ENTRAPPED IN SMALL (DIAMETER <7μM) VESICULAR SYSTEMS

The microencapsulation of drugs in vesicular systems has been extensively investigated for drug targeting and drug delivery. Several authors have found that the pharmacokinetics, metabolism and distribution of the entrapped drug was markedly altered by these systems (Rogerson et a1 1988). To assess these effects we have studied the pharmacokinetics and drug metabolism of antipyrine after entrappment in two small (diameter <7pm) vesicular delivery systems. The systems studied were liposomes and the recently introduced non-ionic surfactant vesicles (NISV). The vesicular systems were prepared by the standard handshaking technique and then reduced in size by sonication. Vesicles composition was a 7:2:1 molar ratio of phosphatidyl choline: cholesterol: dicetyl phosphate for the liposomes and Surfactant IV: cholesterol: dicetyl phosphate for the NISV. The free and entrapped drug were adminsitered to male New Zealand White rabbits at a dose of 12.5mg/kg by IV injection via the marginal ear vein. Blood samples were withdrawn from the vein at various time intervals and a 24 hour urine sample collected by the use of a metabolic cage. The animal was allowed a 7 day recovery period between each experiment. Blood and urine samples were analysed for antipyrine and metabolites using the HPLC method of Teunissen