Lipophilic prodrugs designed for intestinal lymphatic transport

Advanced Drug Delivery Reviews

Volumn 19, Issue 2, 1996, Pages 149-169

  Charman, William N ^a   Porter, Christopher J H ^a  

^a MONASH UNIVERSITY   (Australia)

Author keywords

Lipid; Lipid formulation; Lipoprotein; Lymph; Prodrug

Indexed keywords

ABSORPTION; ANTIBIOTICS; BLOOD VESSELS; DERIVATIVES; DRUG THERAPY; LIPIDS; METABOLISM; PROTEINS;

INTESTINAL LYMPHATIC TRANSPORT; LIPID FORMULATION; LIPOPHILIC PRODRUGS; LIPOPROTEIN; LYMPH; ORAL ADMINISTRATION; XENABIOTICS;

DRUG PRODUCTS;

1 (ALPHA METHYL 4 MYRISTYLOXYCINNAMOYL)GLYCEROL; 4 AMINOBUTYRIC ACID; ACYLGLYCEROL; ALPHA TOCOPHEROL; CHLORAMBUCIL; DIPALMITOYLPHOSPHATIDYLFLUOROURIDINE; EPITIOSTANOL; LEVODOPA; LIPID; LIPOPROTEIN; LK A; MELPHALAN; MEPITIOSTANE; NAPROXEN; PHOSPHOLIPID; PRODRUG; RETINOL; TESTOSTERONE; UNCLASSIFIED DRUG; VITAMIN K GROUP;

DRUG ABSORPTION; DRUG CLEARANCE; DRUG DELIVERY SYSTEM; DRUG METABOLISM; DRUG STABILITY; INTESTINE ABSORPTION; INTESTINE CELL; LIPID ABSORPTION; LIPID METABOLISM; LIPID TRANSPORT; LIPOPHILICITY; LYMPHATIC SYSTEM; MESENTERY LYMPH NODE; PHARMACEUTICS; PHARMACOKINETICS; PRIORITY JOURNAL; REVIEW;

EID: 0343408485     PISSN: 0169409X     EISSN: None     Source Type: Journal    
DOI: 10.1016/0169-409X(95)00105-G     Document Type: Review

References (82)

1. Ueda, C.T., Lemaire, M., Gsell, G. and Nussbaumer, K. (1983) Intestinal lymphatic absorption of cyclosporin A following oral administration in an olive oil solution to rats. Biopharm. Drug. Dispos. 4, 113-124.
2. Grimus, R.C. and Schuster, I. (1984) The role of the lymphatic transport in the enterai absorption of naftifine by the rat. Xenobiotica, 14, 287-294.
3. Palin, K.J. and Wilson, C.J. (1984) The effect of different oils on the absorption of probucol in the rat. J. Pharm. Pharmacol, 36, 641-643.
4. Ichihashi, T., Kinoshita, H., Takagishi, Y. and Yamada, H. (1992) Effect of oily vehicles on absorption of mepitiostane by the lymphatic system in rats. J. Pharm. Pharmacol. 44, 560-564.
5. Ichihashi, T., Kinoshita, H., Takagishi, Y. and Yamada, H. (1992) Effect of bile on absorption of mepitiostane by the lymphatic system in rats. J. Pharm. Pharmacol. 44, 566-569.
6. Kuksis, A. (1987) Absorption of fat soluble vitamins. In: A. Kuksis (Ed), Fat Absorption, Vol. 2, CRC Press, Boca Raton, FL, Chap. 3.
7. Porter, C.J.H., Charman, S.A. and Charman W.N. (1995) Lymphatic transport of halofantrine in the triple-cannulated anesthetized rat model: Effect of lipid vehicle dispersion. J. Pharm. Sci., in press.
8. Sieber, S.M. (1976) The lymphatic absorption of p,p-DDT and some structurally-related compounds in the rat. Pharmacology 14, 443-454.
9. Charman, W.N., Noguchi, T. and Stella, V.J. (1986) An experimental system designed to study the in situ intestinal lymphatic transport of drugs in anesthetized rats. Int. J. Pharm. 33, 155-164.
10. Charman, W.N. and Stella, V.J. (1986) Effect of lipid class and lipid vehicle volume on the intestinal lymphatic transport of DDT. Int. J. Pharm. 33, 165-172.
11. Laher, J.M., Rigler, M.W., Vetter, R.D., Barrowman, J.A. and Patton, J.S. (1984) Similar bioavailability and lymphatic transport of benzo(a)pyrene when administered to rats in different amounts of dietary fat. J. Lipid Res. 25, 1337-1342.
12. Busbee, D.L., Yoo, J.-S., H., Norman, J.O. and Joe, C.O. (1985) Polychlorinated biphenyl uptake and transport by lymph and plasma components. Proc. Soc. Exp. Biol. Med. 179 116-122.
13. Charman, W.N. (1992) Lipid vehicle and formulation effects on intestinal lymphatic drug transport. In: W.N. Charman and V.J. Stella (Eds), Lymphatic Transport of Drugs, CRC Press, Boca Raton, FL, pp. 113-179.
14. Shiau, Y.-F. (1981) Mechanism of intestinal fat absorption. Am. J. Physiol. 240, G1-G9.
15. Bisgaier, C.L. and Glickman, R.M. (1983) Intestinal synthesis, secretion and transport of lipoproteins. Annu. Rev. Physiol. 45, 625-636.
16. Thomson, A.B.R., Keelan, M., Garg, M.L. and Clandinin. M.T. (1989) Intestinal aspects of lipid absorption: in review. Can, J. Physiol. Pharmacol. 67, 179-191.
17. Tso, P. (1994) Intestinal lipid absorption. In: L.R. Johnson (Ed.), Physiology of the Gastrointestinal Tract, Raven Press, New York, pp. 1867-1908.
18. Carey, M.C., Small, D.M. and Bliss, C.M. (1983) Lipid digestion and absorption. Annu. Rev. Physiol. 45, 651-677.
19. Hoffman, A.F. (1978) Lipase, colipase, amphipathic dietary proteins and bile acids: new interactions at an old interface. Gastroenterology 75, 530-532.
20. Borstrom, B., Erlanson-Albertsson, C. and Wieloch, T. (1979) Pancreatic co-lipase: chemistry and physiology. J. Lipid Res. 20, 805-816.
21. Hoffman, N.E. (1970) The relationship between uptake in vitro of oleic acid and micellar solubilization. Biochim. Biophys. Acta 196, 193-203.
22. Wilson, F.A. and Dietschy, J.M. (1972) Characterization of bile acid absorption across the unstirred water layer and brush border of the rat jejunum. J. Clin. Invest. 51, 3015-3025.
23. McDonald, G.B. and Weidman, M. (1987) Partitioning of polar fatty acids into lymph and portal vein after intestinal absorption in the rat. Q. J. Exp. Physiol. 72, 153-159.
24. McDonald, G.B., Saunders, D.R., Weidman, M. and Fisher, L. (1980) Portal venous transport of long-chain fatty acids absorbed from rat intestine. Am. J. Physiol. 239, G141-G150.
25. Bugaut, M. and Carlier, H. (1987) Role of intestinal hydrolases, endogenous substrates, and chyloportal partition in fat absorption. In: A. Kuksis (Ed.), Fat Absorption, Vol. 1, CRC Press, Boca Raton, FL, Chap. 7.
26. Zilvermist, D.B. (1965) The composition and structure of lymph chylomicrons in dog, rat and man. J. Clin. Invest. 44, 1610-1622.
27. Tso, P. and Scobey, M. (1987) The role of phosphatidylcholine in the absorption and transport of dietary fat. In: A. Kuksis (Ed.), Fat Absorption, Vol. 2, CRC Press, Boca Raton, FL, Chap. 6.
28. Sakai, A., Mori, N., Shuto, S. and Suzuki, T. (1993) Deacylation-reacylation cycle: A possible absorption mechanism for the novel lymphotropic antitumor agent dipalmitoyl-phosphatidylfluorouridine in rats. J. Pharm. Sci. 82, 575-578.
29. Noguchi, T., Charman, W.N. and Stella, V.J. (1985) Lymphatic appearance of DDT in thoracic and mesenteric lymph duct cannulated rats. Int. J. Pharm. 24, 185-192.
30. Raub, T.J., Douglas, S.L., Melchior, G.W., Charman, W.N. and Morozowich, W. (1992) Methodologies for assessing intestinal lymphatic transport. In: W.N. Charman and V.J. Stella (Eds), Lymphatic Transport of Drugs, CRC Press, Boca Raton, FL, pp. 63-111.
31. Charman, W.N. and Stella, V.J. (1986) Estimating the maximal potential for intestinal lymphatic transport of lipophilic drug molecules. Int. J. Pharm. 34, 175-178.
32. Charman, W.N. and Stella, V.J. (1991) Transport of lipophilic molecules by the intestinal lymphatic system. Adv. Drug Deliv. Rev. 7, 1-14
33. Dagett, P.R., Wheeler, M.J. and Naborro, J.D.N. (1978) Oral testosterone, a reappraisal. Hormone Res. 9, 121-129.
34. Schurmeyer, T. and Nieschlag, E. (1984) Comparative pharmacokinetics of testosterone enanthate and testosterone cyclohexanecarboxylate as assessed by serum and salivary testosterone levels in normal man. Int. J. Androl. 7, 181-187.
35. Coert, A., Geelen, J., De Vissier, J. and Van der Vies, J. (1975) The pharmacology and metabolism of testosterone-undecanoate (TU), a new orally active androgen. Acta Endocrinol. 79, 789-800.
36. Sieber, S.M., Cohn, V.H. and Wynn, W.T. (1974) The entry of foreign compounds into the thoracic duct lymph of the rat. Xenobiotica 4, 265-284.
37. Tauber, U., Schroder, K., Dusterberg, B. and Matthes, H. (1986) Absolute bioavailability of testosterone after oral administration of testosterone-undecanoate and testosterone. Eur. J. Drug Metab. Pharmacokinet. 11, 145-149.
38. Geelen, J., Coert, A., Meijer, R. and Van der Vies, J. (1977) Comparison of the metabolism of testosterone undecanoate and testosterone in the gastrointestinal wall of the rat in vitro and in vivo. Acta Endocrinol. 86, 216-224.
39. Horst, H.J., Holte, W.J., Dennis, M., Coert, A.., Geelen, J. and Voigt, K.D. (1976) Lymphatic absorption and metabolism of orally administered testosterone undecanoate in man. Klin Wochenschr. 54, 875-879.
40. Noguchi, T., Charman, W.N. and Stella, V.J. (1985) Effect of drug lipophilicity and lipid vehicles on the lymphatic absorption of various testosterone esters. Int. J. Pharm. 24, 173-184.
41. Ichihashi, T., Kinoshita, H., Shimamura, K. and Yamada, H. (1991) Absorption and disposition of epithiosteroids in rats (1): Route of administration and plasma levels of epitiostanol. Xenobiotica 21, 865-872.
42. Ichihashi, T., Kinoshita, H. and Yamada, H. (1991) Absorption and disposition of epithiosteroids in rats (2): Avoidance of first-pass metabolism of mepitiostane by lymphatic absorption. Xenobiotica 21, 873-880.
43. Bruni, G., Galletti, E. and Ercoli, A. (1966) Steroidal ethers: excretion of 17-keto-steroids in man after oral administration in oil solution or in solid state of androstene-dione and its 3-cyclopentyl enol ether. Eur. J. Steroids 1, 29-36.
44. Bruni, G. and Galletti, F. (1970) Steroidal ethers: Urinary excretion of pregnanediols in man after ingestion of quingestrone in fasting and non-fasting conditions. Steroidologia 1, 89-93.
45. Caie, E. and Klopper, A. (1964) The urinary excretion of pregnanediol after the administration of an oral gestagen (progesterone cyclopentyl enol ether). J. Endocrinol. 28, 221-222.
46. Stella, V.J. and Pochopin, N.L. (1992) Lipophilic prodrugs and the promotion of intestinal lymphatic drug transport. In: W.N. Charman and V.J. Stella (Eds), Lymphatic Transport of Drugs, CRC Press, Boca Raton, FL, pp. 182-210.
47. Fernandez, E. and Borgstrom, B. (1990) Intestinal absorption of retinol and retinyl palmitate. Effects of tetrahydrolipstatin. Lipids 25, 549-552.
48. 2-α-tocopheryl esters in the rat. Lipids 10, 627-633.
49. Gallo-Torres, H.E. (1970) Obligatory role of bile for the intestinal absorption of vitamin E. Lipids 5, 379-384.
50. 2-α-tocopheryl nicotinate in the rat. Int. J. Vitam. Nutr. Res. 40, 505-514.
51. Hasegawa, J., Tomono, Y., Fujita, T., Sugiyama, K. and Hamamura, K. (1981) The effect of food on the absorption of α-tocopheryl nicotinate in beagle dogs and human volunteers. Int.J. Clin. Pharmacol. Ther. Toxicol. 19, 216-219.
52. Mathias, P.M., Harries, J.T., Peters, T.J. and Muller, D.P.R. (1981) Studies on the in vivo absorption and micellar solutions of tocopherol and tocopherol acetate in the rat: demonstration and partial characterisation of a mucosal esterase localised to the endoplasmic reticulum of the enterocyte. J. Lipid Res. 22, 829-837.
53. Fukui, E., Kurohara, H., Kareyu, A., Kurisaki, Y., Nakayaman T. and Kimura, T. (1989) Enhancing effect of medium-chain triglycerides on intestinal absorption of d-α-tocopherol acetate from lecithin-dispersed preparations in the rat. J. Pharmacobio-Dyn. 12, 80-86.
54. Gallo-Torres, H.E., Ludorf, J. and Brain, M. (1978). The effect of medium chain triglycerides on the bioavailability of vitamin E. Int. J. Vit. Nutr. Res. 48, 240-249.
55. Tadakazu, T., Machida, Y., Tsushima, Y., Kayano, M. and Nagai, T. (1987) Intestinal absorption of tocopherol in beagle dog and effect of dosage form. Chem. Pharm. Bull. 35, 4592-4596.
56. Kimura, T., Fukui, E., Kageyu, A., Kurohara, H., Kurosaki, Y., Nakayama, T., Morita, Y., Shibusawa, K., Ohsawa, S. and Takeda, Y. (1989). Enhancement or oral bioavailability of d-α-tocopheryl acetate by lecithin-dispersed aqueous preparation containing medium chain triglycerides in rats. Chem. Pharm. Bull. 37, 439-41.
57. Mishima, M., Kobayashi, S., Abe, S. and Yamato, C. (1990) Metabolic fate of indometacin farnesil, a prodrug of indomethacin: characteristic biotransformation of indometacin farnesil in rats. Xenobiotica 20, 135-146.
58. Kumakura, S., Mishima, M., Kobayashi, S., Shirota, H., Abe, S., Yamada, K. and Tsurufuji, S. (1990) Inhibitory effect of indometacin farnesil, a novel antiinflammatory prodrug, on carrageenin-induced inflammation in rats. Agents Actions 29, 286-291.
59. Mishima, M., Kobayashi, S., Hashida, R., Yuzuriha, T., Sato, T. and Satoh, T. (1991) Enzymatic hydrolysis of indometacin farnesil, a prodrug of indomethacin, by carboxylesterase in cultured synovial cells. Res. Commun. Chem. Pathol. Pharmacol. 72, 183-190.
60. Yanagawa, A., Endou, T., Kanemitsu, K., Fukumura, T., Matsui, H., Shoji, Y., Uemura, H., Hori, S. and Nakagawa, T. (1992) A comparative placebo-controlled endoscopic evaluation of damaging effects of indometacin farnesil on the gastric and duodenal mucosa. Ensho 12, 183-190.
61. Murukami, M., Oketani, K., Fujisaki, H., Wakabayashi, T., Sano, N., Watanabe, R. and Katoh, Y. (1988) Indometacin farnesil, a new anti-inflammatory prodrug: effect on gastrointestinal mucosa in rats. Oyo Yakuri 36, 433-438.
62. Garzon-Abureh, A., Poupaert, J.H., Claesen, M. and Dumont, P. (1986) A lymphotropic prodrug of L-Dopa: Synthesis, pharmacological properties, and pharmacokinetic behavior of 1,3-dihexadecanoyl-2-[(S)-2-amino-3-(3,4-dihydroxyphenyl)propanoyl]propane-1,2, 3-triol. J. Med. Chem. 29, 687-691.
63. Sugihara, J., Furuuchi, S., Nakano, K. and Harigaya, S. (1988) Studies on the intestinal lymphatic absorption of drugs. I. Lymphatic absorption of alkyl ester derivatives and α-monoglyceride derivatives of drugs. J. Pharmacobio-Dyn. 11, 369-376.
64. Sugihara, J., Furuuchi, S., Ando, H., Takashima, K. and Harigaya, S. (1988) Studies on the intestinal lymphatic absorption of drugs. II. Glyceride prodrugs for improving the lymphatic absorption of naproxen and nicotinic acid. J. Pharmacobio-Dyn. 11, 555-562.
65. Mizobe, M., Matsuda, S., Yoneyama, T. and Kohno, K. (1983) Evaluation of the bioavailability of hypolipidemic compound, LK-903. Chem. Pharm. Bull. 31, 2424-2431.
66. Sugihara, J. and Furuuchi, S. (1988). Lymphatic absorption of hypolipidemic compound, 1-O-[p-(myristyloxy)-α-methylcinnamoyl]glycerol (LK-903). J. Pharmacobio-Dyn. 11, 121-130.
67. Ross, A.C.and Zilvermist, D.B. (1977) Use of esterified retinol to trace the degradation of chylomicrons in cholesterol-fed rabbits. In: G.W. Manning and M.D. Hause (Eds), Atherosclerosis, Plenum Press, New York, pp. 142-145.
68. Vost, A. and Maclean, N. (1984) Hydrocarbon transport in chylomicrons and high-density lipoproteins. Lipids 19, 423-435.
69. Lindena, J. and Trautschold, I. (1983) Enzymes in lymph: A review. J. Clin. Chem. Clin. Biochem. 21, 327-346.
70. Lindena, J. and Trautschold, I. (1983) Ductus thoracicus lymph in mice. 2. Enzyme activities and protein content. Lymphology 16, 247-249.
71. Garzon-Abureh, A., Poupaert, J.H., Claesen, M., Dumont, P. and Atassi, G. (1983) 1,3-Dipalmitoylglycerol ester of chlorambucil as a lymphotropic, orally administrable antineoplastic agent. J. Med. Chem. 26, 1200-1203.
72. Deverre, J.R., Loiseau, P., Puisieux, F., Gayral, P., Letourneux, Y., Couvreur, P. and Benoit, J.P. (1992) Synthesis of the orally macofilaricidal and stable glycerolipidic prodrug of melphalan, 1,3-dipalmitoyl-2-(4′-(bis(2″-chloroethyl)amino)phenylalaninoyl) glycerol. Arzneim.-Forsch. 42, 1153-1156.
73. Deverre, J.R., Gulik, A., Letourneux, Y., Couvreur, P. and Benoit, J.P. (1991) Synthesis and aqueous organization of 1,3-dipalmitoyl-2-(4-aminobutyryl)glycerol · HCl: A diglyceride prodrug. Chem. Phys. Lipids 59, 75-81.
74. Deverre, J.R., Loiseau, P., Couvreur, P., Letourneux, Y., Gayral, P. and Benoit, J.P. (1989) In vitro evaluation of filaricidal activity of GABA and 1,3-dipalmitoyl-2-(4-aminobutyryl)glycerol · HCl: a diglyceride prodrug. J. Pharm. Pharmacol. 41, 191-193.
75. Jacob, J.N., Hesse, G.W. and Shashoua, V.E. (1990) Synthesis, brain uptake, and pharmacological properties of a glyceryl lipid containing GABA and the GABA-T inhibitor, γ-vinyl-GABA. J. Med. Chem. 33, 733-736.
76. Elkihel, L., Loiseau, P.M., Bourass, J., Gayral, P. and Letourneux, Y. (1994) Synthesis and orally macrofilaricidal evaluation of niclosamide lymphotropic prodrugs. Arzneim.-Forsch. 44, 1259-1264.
77. Mergen, F., Lambert, D.M., Saraiva, J.C.G., Poupaert, J.H. and Dumont P. (1991) Antiepileptic activity of 1,2-dihexadecanoylamino-2-valproyl-propan-2-ol, a prodrug of valproic acid endowed with tropism for the central nervous system. J. Pharm. Pharmacol. 43, 815-816.
78. 14C]carboxybenzoyl)glycerol. J. Pharm. Pharmacol. 30, 743-758.
79. Paris, G.Y., Carmaise, D.L., Cimon, D.G., Swett, L., Carter, G.W. and Young, P. (1979) Glycerides as prodrugs. 1. Synthesis and anti-inflammatory activity of 1,3-bis(alkanoyl)-2-(O-acetylsalicoyl)glycerides (aspirin glycerides). J. Med Chem. 22, 683-687.
80. Paris, G.Y., Carmaise, D.L., Cimon, D.G., Swett, L., Carter, G.W. and Young, P. (1980) Glycerides as prodrugs. 2. 1,3-Dialkanoyl-2-(2-methyl-4-oxo-1,3-benzodioxan-2-yl)glycerides (cyclic aspirin glycerides) as antiinflammatory agents. J. Med Chem. 23, 79-82.
81. Paris, G.Y., Carmaise, D.L., Cimon, D.G., Swett, L., Carter, G.W. and Young, P. (1980) Glycerides as prodrugs. 3. Synthesis and anti-inflammatory activity of [1-(p-chlorobenzoyl)-5-methoxy-2-methylindole-3-acetyl]glycerides (indomethacin glycerides). J. Med Chem. 23, 9-12.
82. Shuto, S., Itoh, H., Ueda, S., Imamura, S., Fukukawa, K., Tsujino, M., Matsuda, A. and Ueda, T. (1988) A facile enzymatic synthesis of 5′-(3-sn-phosphatidyl)nucleosides and their antileukemic activities. Chem. Pharm. Bull. 36, 209-217.