Abstract
Pharmacokinetic studies were performed in male and female WISTAR rats in order to determine the portion of intact absorption of orally applied polyunsaturated phosphatidylcholine (PU-PC), i.e. essential phospholipids (EPL). For this purpose 1.2-dilinoleoyl phosphatidylcholine labeled with either 3H or 14C in the fatty acid and with 14C in the choline moieties and the doubly labeled compound were synthesized. The radioactive material was added to EPL. An oral dose of 70 mg/kg was given to the animals after a starvation period of 16 h. The animals were sacrificed at various intervals after dosing, exsanguinated and their organs were removed for lipid extraction and radioactivity determination. Special investigations were performed using the lymph cannulation technique and whole body autoradiography. Further, radioactivity decorporation via faeces, urine and expired air was measured.
The results are the following: The absorption of EPL from the gut was protrahated, because a pool of phospholipids was developing in the intestinal wall. In lymph-cannulated animals more than 90% of the total absorbed acyl label and approximately 50% of total absorbed choline label appeared in the lymph chylomicrons, these ratios being independent of the time after dosing. The choline label was quantitatively found in the lymph PC fraction. Thus, around half of the orally applied PU-PC was absorbed as 1-lyso-PC (with the 1-position remaining intact during absorption). The absorbed 1-lyso-PC was immediately reacylated to give “intact” PU-PC, since no labeled lyso-PC was detected in the lymph and the 2-position was no longer labeled. This absorption yield of around 50% “intact” reacylated PU-PC of the total absorbed radiolabel was independent of time. Thus, from the total absorption yields the following percentages of “intact” PU-PC absorbed from a single oral dose of EPL were measured: 5% after 3.5 h, 17% after 6.5 h, 26% after 9.5 h and around 50% after 19 h.
This is a preview of subscription content, log in via an institution to check access.
Access this chapter
Tax calculation will be finalised at checkout
Purchases are for personal use only
Preview
Unable to display preview. Download preview PDF.
References
Yasugi T. et al. mult.: Effects of EPL on serum lipid. J.New Remedies & Clinics 22, 691 (1973)
Blaton V., Declercq B., Vandamme D., Soetewey F. and Peeters H.: The human plasma lipids and lipoproteins under influence of EPL therapy. In: Phosphatidylcholine — Biochemical and clinical aspects of essential phospholipids; edited by H. Peeters, Springer, Berlin-Heidelberg-New York, (1976)
Hevelke G., Grott E., Machalke K. und Zappe R.: Zur Wirkung essentieller Phospholipide auf den Blutfettgehalt des Menschen. Folia Angiologica Suppl., Vol. VI, 80–87 (1975)
Müting D., Dohn P. und Reikowski J.: Die Wirkung hochdosierter i.v. und oraler Zufuhr essentieller Phospholipide auf den Eiweiß-und Fettstoffwechsel sowie Enzymaktivitäten chronisch Leberkranker. Verh.Dtsch.Ges.Innere Med. 78, 1389–1392 (1972)
Wallnöfer H. and Hanusch M.: “Essentielle” Phospholipide zur Behandlung von Lebererkrankungen. Med.Monatschr. 27, 331–336 (1973)
Samochowiec L., Kadlubowska D. and Rozewicka L.: Investigations in experimental atherosclerosis. Part 1: The effects of phosphatidylcholine (EPL) on experimental atherosclerosis in white rats. Atherosclerosis 23, 305–317 (1976) SAMOCHOWIEC L., KADLUBOWSKA D., ROZEWICKA L., KUZNA W. and SZYSZKA K.: Investigations in experimental atherosclerosis. Part 2: The effect of phosphatidylcholine (EPL) on experimental atherosclerotic changes in miniature pigs. Atherosclerosis 23, 319–331 (1976)
Stafford W.W. and Day C.E.: Regression of atherosclerosis effected by intravenous phospholipid. Artery 1, 106–114 (1975)
Day C.E.: Obstacles to the clinical investigation of phospholipids, Artery 1, 100–102 (1975)
Hölzl J.: Pharmacokinetic studies on phosphatidylcholine and phosphatidylinositol. In: Phosphatidylcholine — Biochemical and clinical aspects of essential phospholipids, edited by H. Peeters, Springer, Berlin-Heidelberg-New York, (1976)
Hölzl J. and Wagener H.: Über den Einbau von intraduodenal appliziertem 14C/32P Polyen-Phosphatidylcholine in die Leber von Ratten und seine Ausscheidung durch die Galle. Z. Naturf. 26b, 1151–1158 (1971)
Chasseaud L.F., Down W.H., Williams J.M., Sacharin R.M. and Franklin E.R.: The metabolic fate of 3H: 14C-essential phospholipid (EPL) in the rat. Res.Rep. NTN4/75379 Huntington Research Centre, 1975, unpublished
Chasseaud L.F., Down W.H. and Sacharin R.M.: The metabolic fate of 3H: 14C-essential phospholipid (EPL) in the rhesus monkey. Res.Rep. NTN 5/75497, Huntington Research Centre, 1975, unpublished
Lekim D. and Graf E.: Zur Pharmakokinetik und antihyperlipämischen Wirkung oral applizierter EPL-Substanz bei Ratten. Arzneimittelforschung 26, (1976), in press
Lekim D., Betzing H. and Stoffel W.: Incorporation of complete phospholipid molecules in cellular membranes of rat liver after uptake from blood serum. Hoppe-Seyler’s Z. Physiol. Chem. 353, 949–964 (1972)
Stoffel W., Lekim D. and Tschung T.S.: A simple chemical method for labelling phosphatidyl choline and sphingomyelin in the choline moiety. Hoppe-Seyler’s Z. Physiol. Chem. 352, 1058–1064 (1971)
Lekim D. and Betzing H.: Synthesis of labelled phosphatidyl-N,N-dimethylethanolamine and phosphatidylcholine. Hoppe-Seyler’s Z. Physiol.Chem. 354, 1490–1492 (1973)
Bollman J.L., Cain J.C. and Grindlay J.H.: Techniques for the collection of lymph from the liver, small intestine or thoracic duct of the rat. J.Lab.Clin.Med. 33, 1349–1352 (1948)
Scow R.O., Stein Y. and Stein O.: Incorporation of dietary lecithin and lysolecithin into lymph chylomicrons in the rat. J.Biol.Chem. 242, 4919–4924 (1967)
Parthasarathy S., Subbaiah P.V. and Ganguly J.: The mechanism of intestinal absorption of phosphatidylcholine in rats. Biochem.J. 140, 503–508 (1974)
Van Golde L.M.G., Van Den Bosch H., Slotboom A.J. and Scherphof G.L.: Synthesis and metabolism of labelled monoacyl-sn-glycero-3-phosphorylcholines. Progr.biochem. Pharmacol. 5, 129–148 (1969)
Wagener H.: Preparation, Distribution and Turnover of Tritium-Labelled “Essential” Phospholipids (EPL). In: Phospholipids — Biochemistry, Experimentation, Clinical Application; edited by G. Schettler, Thieme, Stuttgart, (1972)
Dewailly P., Decoopman E., Desreumaux C. and Fruchart J.C.: Plasma removal of intravenous essential phospholipds in man. In: Phosphatidylcholine — Biochemical and clinical aspects of essential phospholipids; edited by H. Peeters, Springer, Berlin-Heidelberg-New York, (1976)
Author information
Authors and Affiliations
Editor information
Editors and Affiliations
Rights and permissions
Copyright information
© 1976 Springer-Verlag Berlin Heidelberg
About this paper
Cite this paper
Lekim, D. (1976). On the Pharmacokinetics of Orally Applied Essential Phospholipids (EPL). In: Peeters, H. (eds) Phosphatidylcholine. Springer, Berlin, Heidelberg. https://doi.org/10.1007/978-3-642-66424-3_4
Download citation
DOI: https://doi.org/10.1007/978-3-642-66424-3_4
Publisher Name: Springer, Berlin, Heidelberg
Print ISBN: 978-3-642-66426-7
Online ISBN: 978-3-642-66424-3
eBook Packages: Springer Book Archive