Disposition in rat of a new fluorinated, biocompatible, non-ionic telomeric carrier

Abstract

1. The disposition of the new fluorinated, biocompatible, non-ionic telomeric carrier trisacryl conjugate (F-TAC) labelled with ¹³C and ¹⁴C 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 24 h), and that faecal excretion was low (8% within 72 h). After p.o. administration, faecal elimination was significantly increased (30% within 72 h). No radioactivity was eliminated as ¹⁴CO₂, after either route of administration.

3. After i.v. administration, plasma radioactivity exhibited a biphasic decrease, with t_1/2 = 20 min for the first phase and 29.5 h for the second phase. The maximal plasma concentration was obtained 40 min after oral dosing, followed by a monoexponennal 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. ¹³C- and ¹⁹F-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.