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Bioavailability of Seocalcitol IV: Evaluation of Lymphatic Transport in Conscious Rats

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Abstract

Purpose

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

Materials and Methods

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

Results

A statistically significantly (p  <  0.05) higher recovery of the dosed 3H-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 3H-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 3H-seocalcitol compared with the PG solution. However, even though LCT facilitates the formation of chylomicrons, 3H-seocalcitol favours absorption directly to the portal blood probably due to the moderate lipophilicity of the molecule.

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Abbreviations

AUC:

area under the serum concentration–time curve

LCT:

long chain triglycerides

PG:

propylene glycol

TG:

triglycerides

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Acknowledgments

The authors wish to thank ATV (The Danish Academy of Technical Sciences) for financial support. The radio-labelled compound was kindly synthesized by Dr. Gunnar Grue–Sørensen, LEO Pharma A/S. Mirja Hansen Andersen, LEO Pharma A/S, is thanked for skilful help with animal surgery and dosing. Tina Dahlerup Poulsen, LEO Pharma A/S, is thanked for calculating the VolSurf descriptors.

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Correspondence to Anette Müllertz.

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Grove, M., Nielsen, J.L., Pedersen, G.P. et al. Bioavailability of Seocalcitol IV: Evaluation of Lymphatic Transport in Conscious Rats. Pharm Res 23, 2681–2688 (2006). https://doi.org/10.1007/s11095-006-9109-z

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  • DOI: https://doi.org/10.1007/s11095-006-9109-z

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