Quantitative structure--pharmacokinetic relationship of a series of sulfonamides in the rat

The pharmacokinetics of a series of sulfonamides were investigated after intravenous administration of a 7 mg/kg dose of individual sulfonamides to cannulated female lean Zucker rats. The concentrations of the sulfonamides in blood were determined by colorimetry. The blood concentration-time curves were fitted to a biexponential equation. The partition coefficient, log P, and pKa values of the sulfonamides were taken from the literature, log P and pKa values differed markedly across the series. The extent of protein binding varied enormously, increasing with partition coefficient. There was no significant relationship between the volume of distribution and partition coefficient. However, when the influence of protein binding on volume of distribution was eliminated, a significant linear relationship emerged. Total clearance formed a relatively complex nonlinear relationship with partition coefficient. The relationship of elimination half-life and partition coefficient was inverse of that between clearance and partition coefficient because of a lack of significant relationship between volume of distribution and partition coefficient.     

The effect of glycerol, propylene glycol and polyethylene glycol 400 on the partition coefficient of benzophenone-3 (oxybenzone)

Sunscreen products are widely used to protect the skin from sun-related deleterious effects. The objective of the study was to investigate the potential effect of glycerol, propylene glycol and polyethylene glycol 400 on dermal absorption of oxybenzone by studying their effects on its partition coefficient. The partition coefficient was evaluated in a chloroform-water system at room temperature. It was found that glycerol and propylene glycol decreased the partition coefficient of oxybenzone, while an increase in partition coefficient was observed with polyethylene glycol 400. The findings suggest that polyethylene glycol 400 in contrast to glycerol and propylene glycol has the potential of increasing the vehicle-skin partition coefficient of oxybenzone when cosmetic products containing such an UV absorber are topically applied to the skin.     

药物分子体积和油水分配系数与经应吸收的关系

以8个对氨基苯甲酸酯化合物为模型药物,测定了它们的辛醇/水分配系数、溶解度及通过大鼠腹部皮肤的渗透速率。用皮肤二层扩散模型,分析药物的经皮渗透系数与分子体积和油水分配系数的关系,导出了以分子体积和油水分配系数预测渗透系数的关系式。药物的渗透系数随分子体积增大而降低。当药物的油水分配系数小时,表现为渗透系数随分配系数的增大而增大;当分配系数大到一定值后,渗透系数不再受分配系数的影响,而随分子体积的增大而减小。     

盐酸莫西沙星在正常和模拟失重大鼠中肠吸收特性研究

目的:研究盐酸莫西沙星在SD大鼠肠道不同部位的吸收特性,并对比盐酸莫西沙星在正常和模拟失重大鼠中肠吸收变化。方法:建立大鼠在体单向肠灌流模型,采用HPLC法分别研究了不同浓度(1,2,4 mg·ml^-1)、不同肠段(十二指肠、空肠、回肠)的盐酸莫西沙星吸收情况,并对比正常和模拟失重1,2,3,4周大鼠的肠吸收变化。结果:不同浓度的盐酸莫西沙星在SD大鼠各肠段的有效渗透系数(Peff)差异无统计学意义(P>0.05),表明盐酸莫西沙星在SD大鼠小肠内吸收无明显变化,且无自身浓度抑制作用,主要以被动转运方式吸收。盐酸莫西沙星在十二指肠、空肠、回肠的吸收相近(P>0.05),莫西沙星不存在特异性的吸收部位。比较正常与各模拟失重组吸收参数发现,模拟失重1周和2周的吸收速率参数(Ka)无明显变化,模拟失重3周时,Ka增大了约1倍,与正常组比较差异有统计学意义(P<0.05),到模拟失重4周时,Ka又接近正常水平。结论:盐酸莫西沙星在大鼠小肠吸收方式以被动转运为主,在肠道中易吸收,且不存在特异性吸收部位。模拟失重会加快莫西沙星在肠道的吸收,且模拟失重3周时,变化最明显。该结果提示机体进入失重环境后有必要随时间调整莫西沙星的服用量。     

人参皂苷Rg1的溶解特性与脂质体包封率关系的研究

目的:研究人参皂苷Rg1油-水分配系数与脂质体包封率的关系。方法:测定人参皂苷Rg1的正辛醇-水分配系数、氯仿-水分配系数,人参皂苷Rg1在水、甲醇、乙醇中的溶解度;采用不同的方法制备脂质体并测定包封率。结果:人参皂苷Rg1油-水分配系数低于0.5,在3种溶剂中微溶;几种制备方法所得人参皂苷Rg1脂质体包封率均较低。结论:人参皂苷Rg1油-水分配系数小,不适合制成脂质体。     

Effect of ethanol on the true diffusion coefficient of diclofenac and its sodium salt in silicone membrane

The effect of ethanol on the diffusion coefficient of free diclofenac (DH) as a hydrophobic drug in a silicone membrane was studied and the value was compared with that of sodium diclofenac (DNa) as a hydrophilic material. The silicone membrane permeation of DH was described as a lipid pathway up to 60% w/w ethanol. The change in the partition coefficient of DH between the silicone membrane and ethanol-aqueous solution as a function of ethanol concentration seems to correspond with that of the partition coefficient of many drugs between octanol and water or a buffer. The apparent diffusion coefficient of DH and DNa in ethanol-aqueous solution was dependent on the ethanol concentration, i.e., it was related to the partition coefficient. The true diffusion coefficient of a lipid layer can be calculated by subtracting the partition coefficient from the apparent diffusion coefficient by changing the ethanol concentration.     

pH值对盐酸小檗碱表观油水分配系数的影响

目的测定盐酸小檗碱在正辛醇-水和正辛醇-缓冲液体系中的表观油水分配系数,为其体内吸收研究提供参考。方法采用HPLC法测定盐酸小檗碱的浓度,采用经典摇瓶法测定盐酸小檗碱在正辛醇-水/缓冲液中的表观油水分配系数。结果在37.0℃时,盐酸小檗碱在水中的表观油水分配系数为0.084(lgPapp=-1.08);在pH值为1.0、2.0、11.0、12.0的缓冲液中,其油水分配系数分别为1.74、1.22、1.91、15.17;在pH值为3.0～10.0时,其油水分配系数极小,变化不大,lgPapp均<0。结论在水及pH值1.0～8.0的缓冲液中,盐酸小檗碱的lgPapp均<1.0,预测其在机体胃肠道并不易被吸收。pH值对盐酸小檗碱的表观油水分配系数有一定影响,在一定范围内,pH增加可使其分配系数增大,在pH 12.0的磷酸盐缓冲液中达到最大(Papp=15.17,lgPapp=1.18)。     

盐酸苯环壬酯油水分配系数的测定及pH值对其的影响

目的： 测定盐酸苯环壬酯油水分配系数,研究不同pH值对药物脂水分配系数的影响,为盐酸苯环壬酯新剂型的处方设计提供理论参考。方法： 本实验采用摇瓶-高效液相色谱法测定盐酸苯环壬酯在不同pH值条件下正辛醇-水/缓冲液体系中的表观脂水分配系数。结果： 盐酸苯环壬酯的脂水分配系数lgP值为1.29±0.16;在pH为1.2,3.0,4.5,5.0,5.5,6.0,6.8,7.0,8.0,9.0的环境中,脂水分配系数lgP值分别为0.31,0.72,1.16,1.34,1.99,2.26,2.22,1.61,2.34,3.24。结论： 盐酸苯环壬酯的脂水分配系数与介质的pH值有关,在pH 4.5~8.0生理条件下,盐酸苯环壬酯的脂溶性较好,水溶性差。     

The dependence of the lipid bilayer membrane: buffer partition coefficient of pentobarbitone on pH and lipid composition.

1 The membrane/buffer partition coefficient of [14C]-pentobarbitone has been determined as a function of the lipid composition of bilayer membranes. 2 A new technique based on ultrafiltration gave comparable results to conventional techniques but required less time for equilbration. 3 The membrane/buffer coefficient was independent of pentobarbitone concentration in the range studies. 4 The apparent partition coefficient varied with pH and was a linear function of the degree of dissociation of pentobarbition. 5 Both the charged and uncharged forms of pentobarbitone partitioned into the membrane, the latter to a much greater extent than the former. 6 At low pH the highest partition coefficient observed was in egg phosphatidylcholine bilayer membranes. 7 Incorporation of cholesterol or phosphatidic acid into phosphatidylcholine membranes greatly reduced the partition coefficient. 8 High pressures do not greatly change these partition coefficients.     

布洛芬平衡溶解度及表观油水分配系数的测定

目的：测定布洛芬在不同pH磷酸盐缓冲溶液中的平衡溶解度与表观油水分配系数。方法采用紫外－可见分光光度法测定布洛芬的质量浓度,气浴恒温振荡－摇瓶法测定布洛芬的平衡溶解度及表观油水分配系数。结果37℃时布洛芬在pH2．0、3．0、4．0、5．0、6．0、6．8、7．4、8．0、9．0缓冲溶液中的平衡溶解度分别为0．05874、0．04078、0．06404、0．1930、1．027、2．551、4．613、3．866、4．409mg? mL －1;表观油水分配系数分别为10．19、17．11、12．55、6．390、4．911、5．976、4．925、2．599、1．716。结论布洛芬在磷酸盐缓冲溶液中的平衡溶解度及表观油水分配系数与介质的pH值相关,介质的pH值的增大,布洛芬的平衡溶解度增大;表观油水分配系数减小。     

沙美特罗和布地奈德的脂质体/水分配系数测定及影响因素考察

目的测定沙美特罗和布地奈德的脂质体/水分配系数(P_L/w)，考察影响两种药物P_L/w的因素，揭示药物与磷脂双分子层的作用机制。方法用平衡透析法测定两种药物在不同脂质体组成和不同介质中的P_L/w。结果两种药物P_L/w随脂质体中胆固醇含量及磷脂饱和程度增加而减小；脂质体表面负电荷、介质pH值及离子强度增加，沙美特罗的P_L/w增加。脂质体表面电荷、介质pH值及离子强度对布地奈德的P_L/w影响较小。结论药物P_L/w受药物性质、脂质体磷脂种类、饱和程度、胆固醇含量和表面电荷以及介质pH和离子强度等因素影响，在测定时应选择与生物膜环境相近的P_L/w测定条件，以反映药物在生物膜中的分配。     

高效液相色谱法测定蝙蝠葛碱的平衡溶解度和油水分配系数

目的:测定蝙蝠葛碱在不同pH条件下的平衡溶解度以及在正辛醇-缓冲液体系中的油水分配系数。方法:采用HPLC法测定蝙蝠葛碱的浓度,以饱和法测定平衡溶解度,采用摇瓶法-HPLC法测定蝙蝠葛碱在正辛醇和水相中浓度,从而计算油水分配系数。结果:37℃下蝙蝠葛碱的平衡溶解度随pH的升高而增大;油水分配系数随pH的升高而增大,在pH 6.8～8.0范围内(小肠的pH环境),蝙蝠葛碱的lgP约为0.5,说明其脂溶性较强。结论:蝙蝠葛碱平衡溶解度和油水分配系数都受pH的影响;本试验所建立的方法可准确测定蝙蝠葛碱的平衡溶解度和油水分配系数,并预测其体内过程。     

川芎嗪平衡溶解度及油/水分配系数的研究

目的测定川芎嗪在不同pH值下的平衡溶解度和油水分配系数(P)。方法采用摇瓶法测定表观溶解度,通过药物分配平衡后在油相和水相中的浓度比,计算油水分配系数。结果川芎嗪在二氯甲烷、乙腈、乙酸乙酯等有机溶剂中溶解度较大,在聚乙二醇400中不溶。在蒸馏水中几乎不溶,随着pH值增大,川芎嗪的溶解度变小;川芎嗪正辛醇溶液质量浓度对川芎嗪油水分配系数无明显影响,pH值对川芎嗪油水分配系数有影响,随pH值增大川芎嗪油水分配系数增大。结论药物在水中的平衡溶解度及油水分配系数与介质的pH值有关,当pH>7.24时,川芎嗪的溶解度陡然下降;当pH>6.8时,药物在油相中分配较多,川芎嗪在正辛醇-水体系中的油水分配系数P=12.33。     

黄芩苷在不同pH值缓冲液中理化常数的测定

目的考察黄芩苷在不同pH值中的平衡溶解度与表观油水分配系数,为制剂研究奠定基础。方法采用摇瓶-紫外分光光度法测定温度为25和37℃时,黄芩苷在不同pH值磷酸盐缓冲溶液中的平衡溶解度及在正辛醇/缓冲液体系中的表观油水分配系数。结果 25℃时,黄芩苷在pH=2.0,3.0,4.0,5.0,6.0,6.8,7.4,8.0和9.0缓冲液中的平衡溶解度分别为0.032,0.034,0.119,0.873,3.329,12.96,11.49,4.605和11.87mg.mL-1,相应条件下表观油水分配系数(P)值分别为0.363,0.244,0.292,0.137,0.057,0.046,0.036,0.028和0.029。37℃时,黄芩苷在pH=2.0,3.0,4.0,5.0,6.0,6.8,7.4,8.0和9.0缓冲液中的平衡溶解度分别为0.028,0.048,0.095,0.950,4.881,14.15,26.65,14.48和17.89mg.mL-1,相应条件下表观油水分配系数(P)值分别为0.234,0.224,0.365,0.103,0.074,0.049,0.034,0.034和0.035。结论黄芩苷的平衡溶解度在酸性及中性条件下受温度影响很小,在碱性条件下随着温度升高而增加;黄芩苷在酸性条件下的P值比在碱性条件下大,Pmax=0.363(T=25℃,pH=2),Pmax=0.365(T=37℃,pH=4),随着碱性的增加P值变化不明显,且温度对黄芩苷的P值几乎无影响。     

人参总皂苷和枸杞多糖的溶解特性与脂质体包封率的关系研究

目的:研究药物的溶解度、油水分配系数与脂质体包封率的关系。方法:测定人参总皂苷和枸杞多糖的溶解度及油水分配系数;采用逆向蒸发法制备人参总皂苷脂质体和枸杞多糖脂质体,并测定各脂质体的包封率。结果:人参总皂苷的油水分配系数为0.45,制得的人参总皂苷脂质体包封率为59.06%;枸杞多糖的油水分配系数为0.98,制得的枸杞多糖脂质体包封率为47.61%。结论:油水分配系数对包封率有一定的影响。     

氟尿嘧啶的脂水分配系数与鼻腔吸收速率常数的相关性研究

目的:考察氟尿嘧啶(5-FU)的脂水分配系数与鼻腔吸收速率常数的关系。方法:测定不同pH值条件下(4、6、7、8、10)5-FU在正辛醇-水中的脂水分配系数;采用大鼠鼻腔在体重循环方法测定不同pH值条件下5-FU鼻腔吸收速率常数,并将2种结果数据进行回归。结果:随着pH值的升高5-FU脂水分配系数及鼻腔吸收速率常数均增大,且二者呈正相关(r=0.9838)。结论:药物鼻腔吸收速度常数与脂水分配系数之间有良好的线性关系。     

Microspheres of Human Serum Albumin with Barbiturates: Effect of Drug Partition Coefficient on Preparation and Drug Release

Abstract— Human serum albumin microspheres were prepared with a series of barbiturates by the thermal denaturation method. The barbiturates were of similar general physicochemical properties but different partition coefficients. The total drug content of microspheres was dependent on the partition coefficient, and an increase in the partition coefficient caused a decrease in the drug content of finished microspheres due to drug migration to the outer organic phase during preparation. The ensemble drug release from microspheres was followed by the paddle method and by potentiometric titration with a pH-stat. Nonlinear regression analysis showed the best fit for the spherical Higuchi equation, especially first-order kinetics (bi-phasic). The drug partition coefficient affected the release in such a way that drugs with higher partition coefficients were released faster and to a greater extent than those with lower coefficients.     

基于HPLC法测定醋酸甲羟孕酮的平衡溶解度与油水分配系数

目的对醋酸甲羟孕酮(MPA)在不同溶剂中的平衡溶解度及其在正辛醇-缓冲液体系中的油水分配系数进行测定。方法采用HPLC法测定MPA的质量浓度,测定MPA在水、有机溶剂、缓冲溶液和加十二烷基硫酸钠的缓冲溶液中的平衡溶解度,采用摇瓶法结合HPLC法测定MPA在正辛醇-缓冲液体系中的质量浓度,从而计算油水分配系数。结果 37℃时,MPA在蒸馏水和丙酮中的平衡溶解度分别为0.52±0.04和238.70±0.47μg·mL~(-1);在体积分数为90%的乙醇溶液中的平衡溶解度最大;在加十二烷基硫酸钠的缓冲溶液中的平衡溶解度增大;在水中的表观油水分配系数为1.99(lgP=0.30),脂溶性较强;在pH值为1.2~6.8的缓冲溶液中,平衡溶解度随pH值的升高而减小,油水分配系数随pH值的升高而增大。结论该实验建立的测定方法可准确测定MPA的平衡溶解度和油水分配系数。     

Determination of the partition coefficient and acid dissociation constants of iodochlorhydroxyquin by an improved partition method

A simple and precise method for determining partition coefficients was developed utilizing a disposable injector. The method was used to determine the partition ratio of iodochlorhydroxyquin between n-decane and phosphate-buffered saline, pH 7.4. The partition ratio was found to be 1750 with a coefficient of variation of 3%. Moreover, it was found that iodochlorhydroxyquin did not associate in n-decane at a concentration less than 1 X 10(-3) M. The acid dissociation constants and the partition coefficient of the undissociated species were determined. These values corresponded well with the values obtained from spectrophotometric methods.     

药物的油—水分配系数与鼻腔吸收研究

以油—水分配系数作为药物理化性质的一个指标,研究其与鼻腔吸收的关系。以脂溶性不同的盐酸地尔硫和对乙酰氨基酚为模型药物,用大鼠鼻腔在体重循环法研究了它们在不同pH条件下的鼻粘膜吸收速度常数,同时也测定了相应条件下的辛醇—水分配系数。结果表明,药物透鼻粘膜能力与其油—水分配系数有良好的相关性(γ=0.9761,n=9),提示鼻腔粘膜的性质与多数生物膜相似,脂溶性大的药物容易通过,而亲水性药物的通透性则较低。