Influence of quinidine,cimetidine, and ketoconazole on the enantioselective pharmacokinetics and metabolism of metoprolol in rats

Metoprolol is a β‐blocker and its racemic mixture is used for the treatment of hypertension. In the present study we investigated the influence of CYP2D and CYP3A on the stereoselective metabolism of metoprolol in rats. Male Wistar rats (n = 6 per group) received racemic metoprolol (15 mg/kg) orally, with or without pretreatment with the CYP inhibitor ketoconazole (50 mg/kg), cimetidine (150 mg/kg), or quinidine (80 mg/kg). Blood samples were collected up to 48 h after metoprolol administration. The plasma concentrations of the stereoisomers of metoprolol, O‐demethylmetoprolol (ODM), α‐hydroxymetoprolol (OHM) (Chiralpak® AD column), and metoprolol acidic metabolite (AODM) (Chiralcel® OD‐R column) were determined by HPLC using fluorescence detection (λ_exc = 229 nm; λ_em = 298 nm). CYP3A inhibition by ketoconazole reduced the plasma concentrations of ODM and AODM and favored the formation of OHM. CYP2D and CYP3A inhibition by cimetidine reduced the plasma concentrations of OHM and AODM and favored the formation of ODM. The inhibition of CYP2D by quinidine reduced the plasma concentrations of OHM and favored the formation of ODM. In conclusion, the results suggest that CYP3A is involved in the formation of ODM and CYP2D is involved in the formation of AODM. Chirality 2009. © 2009 Wiley‐Liss, Inc.     

Influence of N‐hexane inhalation on the enantioselective pharmacokinetics and metabolism of verapamil in rats

Verapamil (VER) is commercialized as a racemic mixture of the (+)‐(R)‐VER and (?)‐(S)‐VER enantiomers. VER is biotransformed into norverapamil (NOR) and other metabolites through CYP‐dependent pathways. N‐hexane is a solvent that can alter the metabolism of CYP‐dependent drugs. The present study investigated the influence of n‐hexane (nose‐only inhalation exposure chamber at concentrations of 88, 176, and 352 mg/m³) on the kinetic disposition of the (+)‐(R)‐VER, (?)‐(S)‐VER, (R)‐NOR and (S)‐NOR in rats treated with a single dose of racemic VER (10 mg/kg). VER and NOR enantiomers in rat plasma was analyzed by LC‐MS/MS (m/z = 441.3 > 165.5 for the NOR and m/z 455.3 > 165.5 for the VER enantiomers) using a Chiralpak® AD column. Pharmacokinetic analysis was performed using a monocompartmental model. The pharmacokinetics of VER was enantioselective in control rats, with higher plasma proportions of the (?)‐(S)‐VER eutomer (AUC^0?∞ = 250.8 vs. 120.4 ng/ml/h; P ≤ 0.05, Wilcoxon test). The (S)‐NOR metabolite was also found to accumulate in plasma of control animals, with an S/R AUC^0?∞ ratio of 1.5. The pharmacokinetic parameters AUC^0?∞, Cl/F, Vd/F, and t_1/2 obtained for VER and NOR enantiomers were not altered by nose‐only exposure to n‐hexane at concentrations of 88, 176, or 352 mg/m³ (P > 0.05, Kruskal‐Wallis test). However, the verapamil kinetic disposition was not enantioselective for the animals exposed to n‐hexane at concentrations equal to or higher than the TLV‐TWA. This finding is relevant considering that the (?)‐(S)‐VER eutomer is 10–20 times more potent than R‐(+)‐VER in terms of its chronotropic effect on atrioventricular conduction in rats and humans. Chirality 2010. © 2009 Wiley‐Liss, Inc.     

Controling the rate of protein release from polyelectrolyte complexes

Extended protein release from readily prepared, water-insoluble complexes with oppositely charged polyions is explored. Using hen egg-white lysozyme as a model, its sustained release from such complexes with a number of polyanions under physiological conditions has been demonstrated and rationalized. The rate of release varies orders of magnitude and is controlled by the nature of the polyanion (decreasing upon increase in its linear charge density, length, and hydrophobicity) and the complex particle size (the larger the particles, the slower the release).     

Artificial neural networks in the modeling and optimization of aspirin extended release tablets with eudragit L 100 as matrix substance

The purpose of the present study was to model the effects of the concentration of Eudragit L 100 and compression pressure as the most important process and formulation variables on the in vitro release profile of aspirin from matrix tables formulated with Eudragit L 100 as matrix substance and to optimize the formulation by artificial neural network. As model formulations, 10 kinds of aspirin matrix tablets were prepared. The amount of Eudragit L 100 and the compression pressure were selected as causal factors. In vitro dissolution time profiles at 4 different sampling times were chosen as responses. A set of release parameters and causal factors were used as tutorial data for the generalized regression neural, network (GRNN) and analyzed using a computer. Observed results of drug release studies indicate that drug release rates vary widely between investigated formulations, with a range of 5 hours to more than 10 hours to complete dissolution. The GRNN model was optimized. The root mean square value for the trained network was 1.12%, which indicated that the optimal GRNN model was reached. Applying the generalized distance function method, the optimal tablet formulation predicted by GRNN was with 5% of Eudragit L 100 and tablet hardness 60N. Calculated difference (f ₁ 2.465) and similarity (f ₂ 85.61) factors indicate that there is no difference between predicted and experimentally observed drug release profiles for the optimal formulation. This work illustrates the potential for an artificial neural network, GRNN, to assist in development of extended release dosage forms.     

Effect of microenvironment pH of swellable and erodable buffered matrices on the release characteristics of diclofenac sodium

The aim of this work is to design pH-dependent swellable and erodable-buffered matrices and to study the effect of the microenvironment pH on the release pattern of diclofenac sodium. Buffered matrix tablets containing diclofenac sodium, physically mixed with hydrophilic polymer (hydroxypropyl methylcellulose [HPMC]) and pH-dependent solubility polymer (Eudragit L100-55) were prepared with different microenvironment pHs. The release of diclofenac sodium from the buffer matrices was studied in phosphate buffer solutions of pH 5.9 and 7.4. The swelling and erosion matrices containing only HPMC and Eudragit L100-55 were studied in phosphate buffer solution of pH similar to the microenvironment pHs of the matrices. Drug release from matrices was found to be linear as a function of time. Amount of drug released was found to be higher in the medium of pH 7.4 than that of pH 5.9. The rate of drug release increased with the increase of the microenvironment pH of the matrices as determined from the slope. The pattern of drug release did not change with the change of microenvironment pH. The swelling and erosion occurred simultaneously from matrices made up of HPMC and Eudragit L100-55. Both extent of swelling and erosion increased with increase of the medium pH. It was concluded from this study that changing the pH within the matrix influenced the rate of release of the drug without affecting the release pattern. Fax: Not Forwarded     

Formulation of controlled-release baclofen matrix tablets: Influence of some hydrophilic polymers on the release rate and in vitro evaluation

This work aims at investigating different types and levels of hydrophilic matrixing agents, including methylcellulose (MC), sodium alginate (Alg), and sodium carboxymethylcellulose (CMC), in an attempt to formulate controlled-release matrix tablets containing 25 mg baclofen. The tablets were prepared by wet granulation. Prior to compression, the prepared granules were evaluated for flow and compression characteristics. In vitro, newly formulated controlled-release tablets were compared with standard commercial tablets (Lioresal and baclofen). The excipients used in this study did not alter physicochemical properties of the drug, as tested by the thermal analysis using differential scanning calorimetry. The flow and compression characteristics of the prepared granules significantly improved by virtue of granulation process. Also, the prepared matrix tablets showed good mechanical properties (hardness and friability). MC- and Alg-based tablet formulations showed high release-retarding efficiency, and good reproducibility and stability of the drug release profiles when stored for 6 months in ambient room conditions, suggesting that MC and Alg are good candidates for preparing modified-release baclofen tablet formulations.     

硫膜和树脂膜控释尿素对小麦产量、品质及氮素利用率的影响

通过田间试验,研究了硫膜和树脂膜控释尿素对小麦产量、品质和耕层土壤无机氮含量及氮素利用率的影响.结果表明：与普通尿素相比,硫膜和树脂膜控释尿素均能显著提高小麦籽粒产量和品质,增产幅度达10.4%～16.5%,小麦籽粒蛋白质和淀粉含量分别提高5.8%～18.9%和0.3%～1.4%;两种控释肥均能有效保持耕层土壤无机氮含量,且其氮素后移的功效满足了小麦生育后期对氮素的需求;有效提高了氮肥偏生产力,降低了土壤氮素依存率（降幅11.0%～17.3%）,提高了氮素利用率（增幅58.2%～101.2%）.其中,树脂膜控释尿素比硫膜控释尿素表现出更好的增产效应,实现了氮素的高效利用.     

Drug release rate influences the pharmacokinetics, biodistribution, therapeutic activity, and toxicity of pegylated liposomal doxorubicin formulations in murine breast cancer

The pharmacokinetics (PK), biodistribution (BD), and therapeutic activity of pegylated liposomal doxorubicin formulations with different drug release rates were studied in an orthotopic 4T1 murine mammary carcinoma model. The focus of these experiments was to study the effects of different release rates on the accumulation of liposomal lipid and doxorubicin (DXR) into the tumor and cutaneous tissues of mice (skin and paws). These tissues were chosen because the clinical formulation of pegylated liposomal doxorubicin (Caelyx)/Doxi) causes mucocutaneous reactions such as palmar-plantar erythrodysesthesia (PPE). Liposomes with different doxorubicin (DXR) leakage rates were prepared by altering liposome fluidity through changing the fatty acyl chain length and/or degree of saturation of the phosphatidylcholine component of the liposome. Liposomes with fast, intermediate, and slow rates of drug release were studied. The plasma PK of the liposomal lipid was similar for all formulations, while the plasma PK of the DXR component was dependent on the liposome formulation. Liposomal lipid accumulated to similar levels in tumor and cutaneous tissues for all three formulations tested, while the liposomes with the slowest rates of DXR release produced the highest DXR concentrations in both cutaneous tissues and in tumor. Liposomes with the fastest drug release rates resulted in low DXR concentrations in cutaneous tissues and tumor. The formulation with intermediate release rates produced unexpected toxicity that was not related to the lipid content of the formulation. The liposomes with the slowest rate of drug leakage had the best therapeutic activity of the formulations tested.     

Influence of endotoxin on the stereoselective pharmacokinetics of oxprenolol,propranolol, and verapamil in the rat

The influence of endotoxin-induced inflammation on the enantioselective pharmacokinetics of propranolol, oxprenolol, and verapamil, which bind to α₁-acid glycoprotein, was studied in the rat. The racemic mixtures were given orally. In the control animals, for propranolol and oxprenolol, the plasma concentrations of the (R)-enantiomer were higher than those of the (S)-enantiomer, while for verapamil the reverse was true. Protein binding and intrinsic clearance are the main factors responsible for this enantioselectivity. After endotoxin treatment, for the three drugs tested the plasma concentrations and the plasma binding of both enantiomers were significantly increased. This effect was more pronounced for (R)-propranolol, (R)-oxprenolol, and (S)-verapamil than for their respective antipodes. The enantioselective effect of endotoxin on the plasma concentrations of the drugs studied seems mainly due to the enantioselective increase in binding to α₁-acid glycoprotein. © 1994 Wiley-Liss, Inc.     

Microcontrolled release of biologically active compounds in chick embryos: beads of 200-microns diameter for the local release of retinoids

A method of controlled release that allows the continuous local application of retinoids (vitamin A derivatives) in living tissues has been developed. Several biocompatible 200-microns-diameter polymeric beads have been tested as possible carriers. Each type of bead was loaded by soaking in an isotopically labeled retinoid solution, washed, and then transferred into tissue culture medium for quantitative release measurements. Positively-charged ion-exchange resins of the Dowex 1 type were found to be the most suitable for the controlled release of retinoic acid, a negatively charged compound. For the controlled release of uncharged retinoids such as retinyl acetate, uncharged acrylic ester polymer beads are preferred; these beads can also be used to release the negatively charged compounds retinoic acid and prostaglandin E1. In all cases, a prolonged release is obtained that persists for more than a day. During this interval, the release is diffusion-controlled, and the total amount of compound released is directly proportional to the amount of the compound that the bead is exposed to during the initial loading step. High-performance liquid chromatography has been used to analyze the nature of the released retinoid. When the positively charged beads are loaded with all-trans-retinoic acid, there is a time-dependent decrease in the proportion of the all-trans isomer released which is due to an increased release of two cis isomers. This isomerization reaction occurs at a considerably slower rate when the uncharged beads are used as carriers. To mimic the conditions under which the local release of retinoic acid causes striking pattern duplications in developing chick wings, beads loaded with isotopically labeled retinoids were manually implanted into a slit cut into wing buds of stage-20 chick embryos. The release rate obtained was comparable to that found in vitro, and a time-dependent accumulation of the released radioactive compound was measured that was confined to the tissue near the site of implantation. All of the beads tested were readily accommodated by the tissue and could be easily removed at any time to terminate the treatment. It is believed that the controlled release of chemicals from such tiny biocompatible implants has a wide potential range of applications in biology.     

Copper release rate needed to inhibit fouling on the west coast of Sweden and control of copper release using zinc oxide

How zinc oxide influences copper release has been tested and the lowest release rate of copper from various combinations of copper and zinc in a paint matrix evaluated, whilst still deterring macrofouling, including barnacles and bryozoans. Copper (I) oxide was added to a generic AF paint in 0, 8.5, 11.7 or 16.3 wt% copper oxide in combination with 0, 10 or 20 wt% zinc oxide and applied on PMMA panels. The results show that zinc influences the release rate of copper. When 10 and 20 wt% zinc was added, the total amount of copper released significantly increased by on average 32 and 47% respectively. All treatments that included copper were successful in deterring macrofouling, including the treatment with the lowest average Cu release rate, ie 4.68 μg cm^?2 day^?1.     

pH响应型蔗渣木质素水凝胶的制备及其对蛋白质的控释性能

该研究以蔗渣木质素和甲基丙烯酸为原料合成了pH敏感型蔗渣木质素/聚甲基丙烯酸水凝胶,对其合成条件、pH敏感性、溶胀-退溶胀性能以及对牛血清蛋白的控释等性质进行研究,并采用红外光谱、扫描电镜等对凝胶进行表征。结果表明:(1)对凝胶溶胀比影响的因素由大到小依次为甲基丙烯酸用量、交联剂用量、催化剂用量、反应的温度、木质素用量。当甲基丙烯酸单体浓度为1.75 mol·L~(-1)、木质素浓度为25 g·L~(-1)、交联剂浓度为3.25×10~(-2)mol·L~(-1)、引发剂浓度为1.25×10~(-2)mol·L~(-1)、反应温度为65℃时,所得水凝胶在模拟肠液中的溶胀比最大(28.16 g·g~(-1))。与不加木质素的聚甲基丙烯酸水凝胶相比,蔗渣木质素/聚甲基丙烯酸水凝胶的溶胀比有所下降,但其敏感pH由4~5碱移至6~8。(2)蔗渣木质素/聚甲基丙烯酸水凝胶的溶胀—退溶胀可逆性受组成的影响较大,但相对于聚甲基丙烯酸水凝胶,蔗渣木质素/聚甲基丙烯酸水凝胶对pH值的敏感响应性更强、响应速率更快,同时能在更短时间内达到溶胀平衡。(3)加入木质素可以提高水凝胶对牛血清蛋白的负载量,所试验的蔗渣木质素/聚甲基丙烯酸水凝胶样品对牛血清蛋白的最大负载量可达577 mg·g~(-1)。(4)牛血清蛋白在12 h后基本可达释放平衡;在模拟胃液中,牛血清蛋白的释放率仅10%,而在模拟肠液中释放率达92%。pH响应型蔗渣木质素/聚甲基丙烯酸水凝胶可以作为口服型蛋白类药物的潜在载体。     

控释掺混尿素对稻、麦土壤氮与酶活性的影响

通过大田试验,共设7个处理,即不施氮、常规施肥以及掺混控释氮肥10%、20%、40%、80%、100%处理,探讨了不同施肥处理对土壤中4种形态氮(全氮、铵态氮、硝态氮、微生物生物量氮)和3种氮功能性酶(脲酶、蛋白酶、硝酸还原酶)活性的影响,以探究控释掺混尿素对稻、麦土壤肥力和环境的影响.结果表明: 土壤全氮在稻、麦全生育期内趋于稳定,且掺混比例20%以上各控释氮肥处理在稻、麦季均无显著差异;掺混40%以上控释氮肥能有效促进稻、麦生育中后期土壤无机氮水平;随稻、麦生育期推进,掺混40%以上控释氮肥处理可显著提高土壤微生物生物量氮,但常规施肥处理的微生物生物量氮整体呈明显下降趋势;掺混40%以上控释氮肥能明显提升稻、麦生育中后期土壤酶活性,土壤蛋白酶与硝酸还原酶活性在作物生育后期均随掺混比例增加而提高,以100%控释氮肥处理土壤酶活性最高.掺混20%以上控释氮肥处理能明显降低水稻季分蘖期脲酶活性,推迟铵态氮峰值期,有利于减少氮损失;掺混40%以上控释氮肥处理均可保障稻、麦生育中后期的氮素供应,刺激土壤脲酶与蛋白酶参与氮素转换,促进了土壤氮素有效性;100%控释氮肥处理对稻、麦生育后期土壤硝酸还原酶活性增加最明显,与掺混40%～80%控释氮肥处理相比,可显著减少小麦季20～40 cm土壤硝态氮残留量,在减少氮素损失方面的效果明显.     

Protracted release of the LHRH agonist avorelin (MF 6001) from two depot formulations in dogs and men

Summary Avorelin is a new superagonist of natural luteinizing-hormone-releasing-hormone. Avorelin has been formulated in high molecular weight polylactic glycolic acid to afford protracted and continuous release of the peptide from subcutaneous implants. Two different formulations (10 and 15 mg) were tested first in dogs and then in men during a clinical phase II trial. Chemical castration was maintained for at least 6 months in dogs with both formulations. A similar duration of activity (approximately 6 months) was observed in men.     

Protracted release of the LHRH agonist avorelin (MF 6001) from two depot formulations in dogs and men

Avorelin is a new superagonist of naturalluteinizing-hormone-releasing-hormone. Avorelin hasbeen formulated in high molecular weight polylactic glycolic acid to afford protracted andcontinuous release of the peptide from subcutaneousimplants. Two different formulations (10 and 15 mg)were tested first in dogs and then in men during aclinical phase II trial. Chemical castration wasmaintained for at least 6 months in dogs withboth formulations. A similar duration of activity(approximately 6 months) was observed in men.     

施用控释氮肥对稻田土壤微生物生物量碳、氮的影响

借助农业部望城红壤水稻土生态环境野外观测试验站的控释氮肥试验,研究了施用控释氮肥对水稻不同生育期间稻田土壤微生物生物量碳、氮动态变化的影响。试验共设5个处理:①CK,(不施氮肥);②Urea(施用尿素);③CRNF(施用与处理②等氮量的控释氮肥);④70%CRNF(施用控释氮肥,用氮量为处理②的70%);⑤50%CRNF+M(施用控释氮肥和猪粪,总氮量为处理②的70%,其中控释氮肥用量为处理②的50%,猪粪含氮量为处理②的20%)。结果表明,施肥后10 d,施氮处理土壤微生物生物量碳和氮均达最高,随生育进程推进逐渐下降,成熟期有一定的回升;施肥初期,施用等氮量的控释氮肥处理(CRNF)土壤微生物量碳、氮含量较尿素处理(Urea)分别增加5.4%和22.5%,而水稻生育中后期,控释氮肥处理(CRNF)土壤微生物量碳、氮含量较尿素处理(Urea)下降幅度大,该处理向地上部提供氮素营养较尿素处理高;施氮量较高的CRNF处理,土壤微生物生物量碳低于控释氮肥节氮处理(70%CRNF),但在大多数取样时期,土壤微生物量氮高于控释氮肥节氮处理(70%CRNF);控释氮肥配施有机肥的节氮处理较其他单施化肥处理显著增加土壤微生物生物量碳、氮含量。控释氮肥与有机肥配施,不仅能节约氮肥用量,而且能明显地提高土壤微生物生物量碳、氮的含量。     

Influence of temporal correlation of synaptic input on the rate and variability of firing in neurons

The spike trains that transmit information between neurons are stochastic. We used the theory of random point processes and simulation methods to investigate the influence of temporal correlation of synaptic input current on firing statistics. The theory accounts for two sources for temporal correlation: synchrony between spikes in presynaptic input trains and the unitary synaptic current time course. Simulations show that slow temporal correlation of synaptic input leads to high variability in firing. In a leaky integrate-and-fire neuron model with spike afterhyperpolarization the theory accurately predicts the firing rate when the spike threshold is higher than two standard deviations of the membrane potential fluctuations. For lower thresholds the spike afterhyperpolarization reduces the firing rate below the theory's predicted level when the synaptic correlation decays rapidly. If the synaptic correlation decays slower than the spike afterhyperpolarization, spike bursts can occur during single broad peaks of input fluctuations, increasing the firing rate over the prediction. Spike bursts lead to a coefficient of variation for the interspike intervals that can exceed one, suggesting an explanation of high coefficient of variation for interspike intervals observed in vivo.     

不同水分条件下控释尿素对夏玉米产量和叶片衰老特性的影响

采用旱棚土柱试验,以郑单958为材料,研究不同水分处理(重度干旱胁迫W₁、轻度干旱胁迫W₂、正常水分条件W₃)和不同控释尿素施氮处理(N₀:不施氮肥;低氮N₁:施纯氮150 kg·hm^-2;中氮N₂:施纯氮225 kg·hm^-2;高氮N₃:施纯氮300 kg·hm^-2)对夏玉米产量及叶片衰老特性的影响.结果表明: 控释尿素与水分耦合对延缓叶片衰老、提高功能叶作用时间和效率以及提高产量方面存在显著互作效应.相同氮素条件下,随着土壤水分含量的增加,夏玉米叶面积指数(LAI)、穗位叶叶绿素含量及超氧化物歧化酶(SOD)活性、过氧化氢酶(CAT)活性、过氧化物酶(POD)活性均显著提高,可溶性蛋白含量增加,而丙二醛(MDA)含量显著降低,产量增加;相同水分条件下,随着施氮量的增加,夏玉米LAI、穗位叶叶绿素含量及各种保护酶活性均显著提高,可溶性蛋白含量增加,而MDA含量显著降低,产量也呈增加趋势.但处理W₃N₃、W₃N₂和W₂N₃之间差异不显著,且相对于其他处理,各项指标(MDA除外)均保持较高水平,MDA含量较低,表明控释尿素与水分的耦合效应有利于维持穗位叶功能,延缓叶片衰老,促进光合产物的生产,进而提高夏玉米产量.综合产量、叶面积指数、叶绿素含量和各种保护酶活性及MDA、可溶性蛋白含量,在土壤含水量为(75±5)%的田间持水量条件下(正常水分),控释尿素施氮量超过225 kg N·hm^-2后,继续增施氮肥不能持续提高花后叶片的保护酶活性,且导致保护酶活性下降加快,MDA含量显著升高,加速植株衰老,不利于氮素的高效利用;在土壤含水量为(55±5)%的田间持水量条件下,控释尿素施氮量在300 kg N·hm^-2条件下水氮耦合效应最佳.     

Influence of short-chain fatty acids and osmolality on mucin release in the rat colon

Summary The influence of short-chain fatty acids (SCFA) and osmolality on mucin release in the rat colon was studied histochemically by determining number of stained mucin-containing cells. SCFA did not significantly influence the number of cells staining for mucin. Hypertonic solutions (360 mosm/l) did not affect mucin release in the proximal colon, but stimulated mucin release in the distal colon. Solutions of lower osmolality (300 or 250 mosm/l) caused a considerable release of mucin from goblet cells as well as vacuolated cells in both the proximal and the distal colon; the lower the osmolality, the more mucin was released. The mucosa of the distal colon was conspicuously affected by solutions of lower osmolality. The influence of osmolality on mucin release was entirely local.Supported by a grant from the Deutsche Forschungsgemeinschaft (En 65/9)The authors wish to thank Prof. H. Höller and G. Rechkemmer for critical advice and Miss G. Becker for technical assistanceA preliminary portion of this study was presented at the 3rd Meeting of the European Intestinal Transport Group, Southampton, 21.–23. April, 1980     

控释尿素和普通尿素配比对不同氮效率玉米叶片衰老特性和土壤酶活性的影响

控释尿素和普通尿素配比施用可以同步玉米氮素需求,延缓后期衰老,增加产量。本试验以黄淮海区域两种氮效率玉米作为对象,研究控释尿素和普通尿素不同配比对其叶片衰老特性、土壤酶活性和土壤无机氮的影响。试验选取黄淮海主栽玉米品种豫禾988（氮低效）和郑单958（氮高效）作为试验材料,设置6个施氮处理（CK、N180U、N180C1、N180C2、N180C、N300U）,其中CK为不施氮处理,180、300代表施氮水平分别为180 kg/hm²和300 kg/hm²,U代表全尿素处理（基肥：追肥=2：3）,C1、C2分别代表控释氮：尿素氮为1：2和2：1（基肥一次施用）,C代表全控释尿素处理（基肥一次施用）。2018-2019年结果表明：与CK相比,豫禾988在N180C1和郑单958在N180C2处理下,能够在玉米生育后期显著提高穗位叶超氧化物歧化酶（SOD）和过氧化物酶（POD）活性,降低膜脂过氧化物（MDA）含量,同时也增加了土壤无机氮含量、脲酶和蔗糖酶活性。综上所述,针对不同氮效率玉米品种,通过控释尿素和尿素合理配施,利用速效氮和控释氮的释放来延缓玉米功能叶片衰老,延长功能期,提高生育后期土壤无机氮含量和酶活性,共同促进玉米生长,增加玉米产量,其中豫禾988和郑单958分别在N180C1和N180C2处理下效果最佳。