CHARACTERIZATION OF THE INTESTINAL TRANSPORT PARAMETERS FOR SMALL PEPTIDE DRUGS

被引：25

作者：

FRIEDMAN, DI ^{[1
]}

AMIDON, GL ^{[1
]}

机构：

[1] UNIV MICHIGAN,COLL PHARM,ANN ARBOR,MI 48109

来源：

JOURNAL OF CONTROLLED RELEASE | 1990年 / 13卷 / 2-3期

关键词：

absorption kinetics; ACE inhibitors; carrier-mediated transport; oral bioavailability of peptide drugs; β-lactams;

D O I：

10.1016/0168-3659(90)90005-E

中图分类号：

O6 [化学];

学科分类号：

0703 ;

摘要：

Several laboratories have recently shown that many peptides and peptide-similar drugs are well absorbed in the mammalian intestine via the peptide transport system for nutrient small peptide (dipeptides and tripeptides) absorption. This facilitated non-passive transport in the intestine is saturable and concentration dependent, and further characterized by the mutual inhibition of transport among the compounds. Peptide and peptide derivative drugs are often zwitterionic compounds, generally ionized at the intestinal pH and therefore are expected to undergo only limited passive absorption. Nonpassive and passive transport are independent and may occur simultaneously. Peptide drugs that have been shown to be transported by the peptide carrier systems are various β-lactams, the angiotensin converting enzyme (ACE) inhibitors captopril, enalapril, lisinopril and SQ 29,852, TRH and its analogues, and alafosfaline and some of its analogues. The carrier characterization is based upon transport parameters, Km Jmax (or Vmax) and Pc (Michaelis-Menten constant, maximal flux and the carrier permeability constant respectively) determined over the last years for several dipeptides, β-lactam antibiotics and ACE inhibitors. © 1990.

引用

页码：141 / 146

页数：6

共 20 条

[1] Alpers, Digestion and absorption of carbohydrates and proteins, Physiology of the Gastro-Intestinal Tract, pp. 1469-1487, (1987)
[2] Tsuji, Nakashima, Kagami, Yamana, Intestinal absorption mechanism of amino-β-lactam antibiotics. I: Comparative absorption and evidence for saturable transport of amino-β-lactam antibiotics by in situ rat small intestine, J. Pharm. Sci., 70, pp. 768-773, (1981)
[3] Nakashima, Tsuji, Kagatani, Yamana, Intestinal absorption mechanism of amino-β-lactam antibiotics. III. Kinetics of carrier-mediated transport across the rat small intestine in situ, J. Pharm. Dyn., 7, pp. 452-464, (1984)
[4] Nakashima, Tsuji, Mizuo, Yamana, Kinetics and mechanism of in vitro uptake of amino-β-lactam antibiotics by rat small intestine and relation to the intact-peptide transport system, Biochem. Pharmacol., 33, pp. 3345-3352, (1984)
[5] Hu, Sinko, DeMeere, Johnson, Amidon, Membrane permeability for some amino acids and β-lactam antibiotics: application of the boundary layer approach, J. Theor. Biol., 131, pp. 107-114, (1988)
[6] Sinko, Amidon, Characterization of oral absorption of β-lactam antibiotics. I. Cephalosporins. Determination of intrinsic membrane absorption parameters in the rat intestine in situ, Pharm. Res., 5, pp. 645-650, (1988)
[7] Tsuji, Terasaki, Tamai, Hirroka, H<sup>+</sup> gradient dependent and carrier-mediated transport of cefixime, a new cephalosporin antibiotic, across brush-border membrane vesicles from rat small intestine, J. Pharmacol. Exp. Ther., 241, pp. 594-601, (1986)
[8] Humphrey, Ringrose, Peptides and related drugs A review of their absorption metabolism and excretion, Drug Metabolism Reviews, 11, pp. 283-310, (1986)
[9] Atherton, Hall, Hassall, Holmes, Lambert, Lloyd, Ringrose, Phosphonopeptide antibacterial agents related to alafosfalin: Design, synthesis, and structure-activity relationship, Antimicrob. Agents Chem., 18, pp. 897-905, (1980)
[10] Hu, Amidon, Intestinal absorption of captopril in rats, J. Pharm. Sci., 77, pp. 1007-1011, (1988)

← 1 2 →