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101.
102.
目的:研究安乃近溶液弄粘膜吸收规律。方法:以大鼠在体鼻循环法为实验模型,考察循环液的体积、流速等对安乃近弃枯膜吸收的影响。并在体积、流速确定的条件下,考查循环液浓度不同时,安乃近鼻粘膜吸收规律。结果:循环液体积越大,单位时间内粘膜吸收百分率越小;当流速较小时,随着流速的增加,吸收速度常数K增大,流速超过2 . 0 ml · min-1后,K显著减小;以循环液体积为3 ml,流速2.0 ml"min-1,考察了50,100,150,200 g·L-1安乃近溶液弄粘膜吸收规律,表明不同浓度的安乃近鼻粘膜吸收速度为一常数。结论:安乃近溶液鼻粘膜吸收机制为被动扩散,吸收符合一级动力学,吸收速度常数K为0.022 19 min-1 。 相似文献
103.
Krondahl Eva Orzechowski Achim Ekström Gunilla Lennernäs Hans 《Pharmaceutical research》1997,14(12):1780-1785
Purpose. To study intestinal transport and metabolism of three new -selective tetrapeptide enkephalin analogues, LEF537, LEF553 and TAPP These peptides are stabilized against enzymatic hydrolysis by having a D-aminoacid in position 2 and a blocked COOH-terminal.
Methods. We used a single-pass perfusion technique to study the transport of the peptides in rat jejunum. To reduce luminal and/or brush-border metabolism during the perfusion we used protease inhibitors (Pefabloc® SC, bestatin and thiorphan). The rate of metabolism was studied by incubations in rat jejunal homogenate, rat jejunal fluid and human gastric and jejunal fluid with and without these inhibitors.
Results. The jejunal permeabilities (Peff) of the peptides were 0.43–0.78 10–4 cm/s without inhibitors and 0.09–0.45 10–4 cm/s in presence of the inhibitors. All three peptides were rather rapidly degraded by enzymes in rat jejunal homogenate with half-lives of between 11.9 ± 0.5 and 31.7 ± 1.5 min. The addition of inhibitors to the homogenate prolonged the half-lives substantially for LEF553 (167 ± 35 min) and TAPP (147 ± 2 min), but only slightly for LEF537 (16.4 ± 0.5 min). LEF553 and TAPP were both hydrolyzed in rat and human jejunal fluid, while LEF537 was metabolized less in these fluids. When LEF553 and TAPP were incubated with intestinal fluid in the presence of inhibitors, metabolism was almost completely inhibited. There was no metabolism for any of the peptides in human gastric juice.
Conclusions. The replacement of the terminal free carboxylic group with an amide group did not increase the stability of the peptides in jejunal tissue enough to allow successful oral drug delivery. 相似文献
104.
Byron Peter R. Sun Zhuang Katayama Hirokazu Rypacek Frantisek 《Pharmaceutical research》1994,11(2):221-225
The pulmonary absorption kinetics of a single molecular weight distribution (MWD) of fluorophore-labeled poly-,-[N(2-hydroxyethyl)-DL-aspartamide] (F-PHEA), a hydrophilic and biocompatible synthetic polypeptide, were studied in the isolated, perfused rat lung (iprl) as functions of administered polymer concentration, dose, vehicle, and presence and absence of fluorophore. The MWD was characterized before and after absorption by measurement of weight- and number-averaged molecular weights (M
wand M
n, respectively) using high-performance gel-permeation chromatography. Values for M
w and M
n were 8.6 and 5.3 kD before, and 6.7 and 4.7 kD after, absorption into the perfusate; there was no significant metabolism and the MWD of the absorbed polymer was independent of both dose and sampling time over a 3-hr period. F-PHEA failed to show any evidence of aggregation in solution or changes in dose distribution within the airways as functions of increasing polymer concentration and dose. A concentration ranging study indicated the presence of a saturable, carrier-mediated transport process for F-PHEA with a maximum absorption rate, V
max, of approximately 180 µg or 0.027 µmol/hr. Coadministration of fluorophore-free PHEA was capable of depressing the absorption of F-PHEA. The transport process for F-PHEA appeared to have a molecular weight limit of about 7 kD for this hydrophilic polymer. 相似文献
105.
Hovgaard Lars Brøndsted Helle Buur Anders Bundgaard Hans 《Pharmaceutical research》1995,12(3):387-392
A series of O-cyclopropane carboxylic acid ester prodrugs of various -blocking agents was synthesized. All prodrugs were hydrolyzed to give their parent compounds in aqueous phosphate buffer of pH 7.4 and in 80% human plasma. The half-lives in buffer solutions varied from 4 hours for the timolol prodrug to about 1 day for the prodrug of alprenolol. In human plasma the half-lives were shorter, ranging from 1 to 7 hours. The formation of the O-cyclopropane carboxylic acid ester derivatives significantly increased the lipophilicities of the -blockers as measured by the distribution coefficient between n-octanol and aqueous phosphate buffer of pH 7.4. To characterize the biomembrane permeability characteristics of the -blockers, transport properties across Caco-2 cell monolayers were investigated. An increase in lipophilicity resulted in a higher permeability of the prodrugs as compared to the parent compounds. Hence, acebutolol experienced an increment of a factor 17 on the apparent permeability coefficient, Papp, whereas Papp for the more lipophilic drug propranolol was increased by a factor of only 1.26. Some conversion of the prodrugs to their parent compounds was observed during the transport and appeared to be due to enzymatic intracellular metabolism.Deseaced. 相似文献
106.
Purpose. To use the drug kinetics in dermis to predict the in vivo blood concentration after topical administration.
Methods. A two-step pharmacokinetic model was established. The first step was to calculate the drug input rate or flux from the skin to the systemic circulation using the drug kinetic parameters in dermis. These parameters include (a) distance over which the drug concentration declines by 50%, (b) drug concentration at the epidermal-dermal junction, and (c) minimal plateauing drug concentration in the muscle layer. These parameters were experimentally determined from the drug concentration-tissue depth profiles in the dermis, after the application of a topical dose of ddI (200 mg/kg) to rats. The second step was to use the drug input rate together with the systemic disposition pharmacokinetics of ddI in rats to predict the plasma concentration-time profiles. The model-predicted plasma concentration-time profiles were compared with the observed profiles, to determine the validity of the proposed pharmacokinetic model.
Results. The observed steady state concentration (Css) in individual animals (n = 6) deviated from the predicted values by 3 to 55% with 3 of 6 rats showing a <15% deviation. The mean observed Css of all animals deviated from the mean predicted values by less than 15%.
Conclusions. The close agreement between the observed and the model-predicted drug concentrations indicates that the systemic drug input can be calculated from the drug kinetics in the dermis. 相似文献
107.
目的:防止生物样品中的汞在消化过程中的逸失及在测量过程中由于汞的吸附造成器皿的污染。方法:采用消化还原一体化,在恒温水浴锅与自制恒温消化器消化样品,冷原子吸收法测定发中汞。结果:标准偏差小于0.013μg/g;变异小于10.2%;样品加标回收率介于89% ̄106%。结论:本方法有效地防止了汞的逸失及对器皿的污染,精密度与准确度均符合微量分析的要求。 相似文献
108.
活性钙在大鼠体内吸收利用率的研究 总被引:6,自引:0,他引:6
目的对活性钙以度常用钙的朴钙效果进行比较研究.方法 选用3周断乳的wistar大鼠随机分为碳酸钙、醋酸钙、活性钙、磷酸氢钙、乳酸钙和基础6组,分别进行28d喂养及3d代谢实验。结果 活性钙组的增加体重大于磷酸氢钙、醋酸钙和基础组(P<0.05);活性钙的骨钙含量高于磷酸氢钙和基础组(P<0.05);活性钙组钙吸收率为71.7%;净利用丰为71.2%,结论 活性钙是一种良好的钙源,可以广泛用于食品添加剂和补钙药物. 相似文献
109.
Lue?en Henrik. L. de Leeuw Bas. J. Langeme?er Mariska W. E. de Boer A. G. Verhoef J. Coos. Junginger Hans E. 《Pharmaceutical research》1996,13(11):1668-1672
Purpose. To evaluate the effect of the crosslinked poly(acrylate) carbomer 934P (C934P) and its freeze-dried neutralized sodium salt (FNaC934P) as well as chitosan hydrochloride on the intestinal absorption of the peptide drug buserelin.
Methods. Buserelin was applied intraduodenally in control buffer, 0.5% (w/v) C934P, 0.5% (w/v) FNaC934P, 1.5% (w/v) chitosan hydrochloride or FNaC934P/chitosan hydrochloride (1:1 (v/v)) mixture in rats.
Results. All polymer preparation showed a statistically significant improvement of buserelin absorption compared to the control solution. The absolute bioavailabilities for the different polymer preparations were: control, 0.1%; 0.5% FNaC934P, 0.6%; 0.5% C934P, 2.0%; chitosan hydrochloride, 5.1% and FNaC934P/chitosan hydrochloride (1:1 (v/v)) mixture, 1.0%. The higher bioavailability with chitosan hydrochloride compared to C934P and FNaC934P indicates that for buserelin the intestinal transmucosal transport enhancing effect of the polymer plays a more dominant role than the protection against proteases such as -chymotrypsin.
Conclusions. The mucoadhesive polymers carbomer 934P and chitosan hydrochloride are able to enhance the intestinal absorption of buserelin in vivo in rats, and may therefore be promising excipients in peroral delivery systems for peptide drugs. 相似文献
110.
Background: The pharmacokinetic variables of drug clearance and volume of distribution are usually corrected for body weight
or surface area. Only recently have the relationships which exist between body size, physiologic function and pharmacokinetic
variables been evaluated in the obese population. These effects are not widely known, and data on this and the effects of
bariatric surgical procedures are scantily documented in the surgical literature. Methods: Literature review. Results: Drugs
with a low or moderate affinity for adipose tissue have a moderate increase in the volume of distribution (Vd), and this correlates
with the increase in lean body mass (LBM). Highly lipophilic drugs, with some exceptions, show the expected increase in Vd
and prolongation of elimination half-life, indicating a marked distribution into adipose tissue. Drug absorption, in general,
is slowed by delayed gastric emptying and is normal when gastric emptying is normal or increased. Most drug absorption occurs
in the small intestine where duration of drug/mucosal contact is the most important factor. Conclusions: Drugs whose distribution
is restricted to LBM should utilize a loading dose based on ideal body weight (IBW). For those drugs which distribute freely
into adipose tissue, the loading dose should be based on total body weight (TBW). Adjustment of the maintenance dose depends
on clearance rates. In a few cases dosage adjustment depends on pharmacodynamic data, since drug clearance does not conform
to these recommendations, for reasons which remain to be defined. Following bariatric surgery, in the absence of delayed gastric
emptying or uncontrolled diarrhea, drug absorption rates are usually comparable to the non-operated patient. 相似文献