DISPOSITION IN RAT OF A NEW FLUORINATED, BIOCOMPATIBLE, NONIONIC TELOMERIC CARRIER

1. The disposition of the new fluorinated, biocompatible, non-ionic telomeric carrier trisacryl conjugate (F-TAC) labelled with C-13 and C-14 On the amide function has been studied in the rat after p.o. and i.v. administration. 2. After i.v. administration, excretion measurements have shown that radioactivity was eliminated mainly in the urine (69% within 24h), and that faecal excretion was low (8% within 72h). After p.o. administration, faecal elimination was significantly increased (30% within 72h). No radioactivity was eliminated as (CO2)-C-14, after either route of administration. 3. After i.v. administration, plasma radioactivity exhibited a biphasic decrease, with t(1/2) = 20min for the first phase and 29.5h for the second phase. The maximal plasma concentration was obtained 40min after oral dosing, followed by a monoexponential decrease with t(1/2) = 38.1 h. The ratio AUC (p.o.)/AUC (i.v.) as an assessment of bioavailability was 0.22. 4. After both i.v. and p.o. administration, a relatively homogeneous concentration of radioactivity was found in most organs, close or below the plasma concentration, indicating that tissues do not exhibit a high affinity for this molecule. In addition, F-TAC did not cross the blood-brain barrier. 5. Analysis of urine and plasma on DOWEX AG1X2 anionic resin showed that < 20% of the radioactivity was bound to this support. C-13 and F-19-nmr analysis of the non-bound radioactivity identified it to unchanged F-TAC, with bound radioactivity being due to polyanionic telomers arising from the hydrolysis of the amide function. 6. The in vivo stability of the telomeric structure indicates that F-TAC could be used as a drug carrier, both by p.o. and i.v. administration.