Bioavailability of seocalcitol IV: evaluation of lymphatic transport in conscious rats.
OBJECTIVE
To study the use of long chain triglycerides (LCT) as a lymphotropic carrier of (3)H-seocalcitol by comparing the lymphatic transport and the portal absorption of (3)H-seocalcitol when dissolved in a (1) LCT solution or a (2) reference solution without lipid containing propylene glycol (PG).


METHODS
A lymph cannulated conscious rat model was dosed orally with (3)H-seocalcitol dissolved in either LCT or PG. Lymph was collected continuously, and blood was sampled over 9 h. (3)H-seocalcitol in blood and lymph and triglycerides in lymph were analysed.


RESULTS
A statistically significantly (p < 0.05) higher recovery of the dosed (3)H-seocalcitol was found in the intestinal lymph upon administration of the LCT solution (1.3 +/- 0.6%) compared to the PG solution (0.5 +/- 0.4%). The portal absorption of (3)H-seocalcitol was significantly (p < 0.05) higher from the LCT solution (16.2 +/- 2.2%) than from the PG solution (10.8 +/- 0.8%).


CONCLUSIONS
The LCT solution resulted in a statistical significantly higher level of lymphatic and portal transport of (3)H-seocalcitol compared with the PG solution. However, even though LCT facilitates the formation of chylomicrons, (3)H-seocalcitol favours absorption directly to the portal blood probably due to the moderate lipophilicity of the molecule.
Grove
Mette
M
Pharmaceutical Formulation, LEO Pharma A/S, Industriparken 55, 2750, Ballerup, Denmark.
Nielsen
Jeanet L
JL
Pedersen
Gitte P
GP
Müllertz
Anette
A
D000818:Animals; D001682:Biological Availability; D001692:Biological Transport; D002117:Calcitriol / Q000031:analogs & derivatives* / Q000493:pharmacokinetics; D041981:Gastrointestinal Tract / Q000378:metabolism; D008196:Lymph / Q000378:metabolism*; D051381:Rats; D014280:Triglycerides / Q000378:metabolism
D014280:Triglycerides; D002117:Calcitriol; C078903:seocalcitol