NUTRIENT EFFECTS ON INTESTINAL DRUG ABSORPTION

被引:15
作者
FLEISHER, D
LIPPERT, CL
SHETH, N
REPPAS, C
WLODYGA, J
机构
[1] College of Pharmacy, University of Michigan, Ann Arbor
基金
美国国家卫生研究院;
关键词
calcium-drug interaction; drug-nutrient interaction; glucose-drug interaction; intestinal absorption; phenytoin;
D O I
10.1016/0168-3659(90)90119-E
中图分类号
O6 [化学];
学科分类号
0703 ;
摘要
The effect of oral co-administration of nutrients on intestinal drug absorption is a function of drug dissolution, gastrointestinal (GI) residence time and intestinal membrane transport. Nutrient effects on GI residence time may influence the availability of the drug for absorption when dissolution is rate controlling; alternatively, nutrient effects on membrane transport pathways may dictate variability in drug absorption when these pathways are rate limiting. This report describes nutrient effects on the absorption variability of the anticonvulsant-antiarrhythmic drug, phenytoin (PHT). Numerous reports, detailing clinical failure to maintain drug plasma levels within the narrow therapeutic index of PHT, haue implicated phenytoin-nutrient interactions as (possibly) causative. Absorption variability due to limited time for drug dissolution during GI transit was studied by measuring PHT plasma concentrations with time following oral dosage in dogs. Variability in intestinal uptake from PHT solutions as a function of nutrient inclusion was studied by measuring steady-state membrane permeabilities from intestinal perfusions and initial-rate uptakes by intestinal rings in rats. © 1990.
引用
收藏
页码:41 / 49
页数:9
相关论文
共 20 条
[1]  
Sinko, Amidon, Characterization of the oral absorption ofbeta-lactam antibiotics, Pharm. Res., 5, pp. 645-650, (1988)
[2]  
Welling, Interactions affecting drug absorption, Clin. Pharmacokin., 9, pp. 404-434, (1984)
[3]  
Longe, Smith, Phenytoin interaction with an oral feeding results in loss of seizure control, J. Amer. Geriatric Soc., 36, pp. 542-544, (1988)
[4]  
Schwartz, Rhodes, Cooper, Solubility and ionization characteristics of phenytoin, J. Pharm. Sci., 66, pp. 994-997, (1977)
[5]  
Seeman, Chau-Wong, Moyyen, The membrane binding of morphine, diphenylhydantoin and tetrahydrocannabinol, Can. J. Physiol. Pharmacol, 50, pp. 1193-1196, (1972)
[6]  
Pappenheimer, Reiss, Contribution of solvent drag through intercellular junctions to absorption of nutrients by the small intestine of the rat, J. Membrane Biol., 100, pp. 123-136, (1987)
[7]  
Luppa, Muller, Effects of diabetes and adrenocortical state on intestinal transport capacity and (Na<sup>+</sup> −K<sup>+</sup>)-activated adenosine triphosphatase activity, Diabete Metabolisme (Paris), 12, pp. 191-196, (1986)
[8]  
Dressman, Amidon, Radiotelemetric method for evaluating enteric coatings, J. Pharm. Sci., 73, pp. 935-938, (1984)
[9]  
Johnson, Amidon, Determination of intrinsic membrane transport parameters from perfused intestine experiments: a boundary layer approach to estimating the aqueous and unbiased membrane permeabilities, J. Theor. Biol., 131, pp. 93-106, (1988)
[10]  
Levich, Physico-Chemical Hydrodynamics, pp. 60-72, (1962)