Effect of cyclophosphamide administration on the activity and relative content of hepatic P4502D1 in rat

1. The effects of the administration of the anticancer and immunosuppressive drug, cyclophosphamide, to the rat on hepatic P4502D1 activity and content in the microsomal fraction have been examined.

2. Liver microsomes were obtained from male Hooded Wistar rats administered a single dose (i.p.) of saline or cyclophosphamide (200mg/kg). Rats receiving cyclophosphamide were killed 1, 4, 7, 10 or 14 days after cyclophosphamide administration. The O-demethylation of dextromethorphan to dextrorphan was used to monitor 2D1 activity.

3. The mean V_max for dextrorphan formation was reduced significantly (p<0·0001) 7, 10 and 14 days after cyclophosphamide administration compared with the control group (control, 0·32±0·07; 7-day, 0·20±0·08; 10-day, 0·11±0·02; and 14-day group, 0·15 ± 0·02 nmol/mg/min).

4. Western blotting revealed that there was a significant reduction (p < 00005) in the microsomal relative 2D1 content 10 days after cyclophosphamide administration compared with the control group (control, 1·25 ± 0·44; and 10-day group, 0·65 ± 0·14).

5. The activity of reduced nicotinamide adenine dinucleotide phosphate P450 reductase was significantly reduced (p<0·0001) 7, 10 and 14 days following cyclophosphamide administration (control, 215 ± 24; 7-day, 102 ±20; 10-day, 59 ± 4 and 14-day group, 76 ± 8 nmol/mg/min). Cytochrome b₅ content was significantly reduced (p < 0·0001) 7 and 10 days following cyclophosphamide administration (control, 04·6±0·13; 7-day, 0·28 ± 0·07 and 10-day group, 0·20 ± 0·03 nmol/mg).

6. The significant reductions in the activity of rat hepatic microsomal 2D1 following cyclophosphamide administration, as seen by the alterations in mean V_max for dextrorphan formation, do not appear to be due to a single factor, but may result from a combination of several events, including reductions in relative 2D1 content, reduced nicotinamide adenine dinucleotide phosphate P450-reductase activity and cytochrome b₅ content.     

盐酸二甲双胍/格列本脲复方片剂在人体的药代动力学

目的　建立人血浆中格列本脲的HPLC ESI MS测定法 ,研究志愿者口服格列本脲与二甲双胍的复方片剂后的药代动力学行为。方法　人血浆样品中格列本脲的测定方法 :血浆样品以 1mol·L- 1的盐酸酸化后用乙酸乙酯提取 ,进行HPLC ESI MS分析 ,色谱柱为LichrospherC18(dp 5μm ,4 6mmID× 2 5cm ) ,流动相为甲醇 -10mmol·L- 1醋酸铵水溶液 (78∶2 2 ,V/V) ,检测方式为SIM方式 ,检测离子为m/z 492 1(格列本脲 )、m /z 444 1(内标 )。 2 0名健康志愿者交叉口服供试片和参比片 ,剂量均为格列本脲 2 5mg和盐酸二甲双胍 50 0mg。 结果　在 0 3 10～ 413 μg·L- 1范围内格列本脲峰面积与内标峰面积的比值与浓度的线性关系良好。格列本脲受试制剂与参比制剂的T1/2 分别为(5 4± 0 8)h、(5 9± 1 0 )h ,Cmax 分别为 (14 6± 2 2 ) μg·L- 1、(12 3± 16) μg·L- 1,Tmax分别为 (2 7± 0 9)h、(3 0±0 7)h ,AUC0～ 3 6 分别为 (73 0± 14 0 ) μg·h·L- 1、(63 2± 117)μg·h·L- 1;二甲双胍受试制剂与参比制剂的T1/2 分别为(3 0± 0 6)h、(3 0± 0 4)h ,Cmax分别为 (1 61± 0 3 2 )mg·L- 1、(1 62± 0 3 3 )mg·L- 1,Tmax分别为 (1 8± 0 2 )h、(1 7± 0 4)h ,AUC0～ 15 分别为 (7 3 7± 1 3 4 )     

The detection and identification of synthetic steroids in horse urine

A scheme for the detection of synthetic steroids which could be used in the “doping” of race-horses is described. The method involves extraction from urine into ethyl acetate: ether (1:1) followed by initial two-dimensional thin-layer chromatography using (1) ethyl acetate (2) methylene chloride: dioxan: water (100:50:50). Elution of the ultraviolet absorbing spots for extinction measurements is followed by further one way thin-layer chromatography as free alcohols in amyl acetate: acetone (1:1). Further chromatography of the steroid alcohols in chloroform: ether: water (80:20:0·5) on formamide-impregnated plates and chromatography of the acetates in ether helps to identify the unknown steroid. Additional identification is made by colour reactions with (1) a tetrazolium reagent (2) vanillin: perchloric acid.     

HPLC-MS/MS法测定血浆中十肽化合物LXT-101及Beagle犬药代动力学研究

建立HPLC-MS/MS法测定血浆中十肽化合物(LXT-101)的浓度，并应用于Beagle犬的药代动力学研究。血浆样品采用乙腈直接沉淀蛋白的方法，内标(IS)选用¹²⁷I-LXT-101，采用ESI-MS/MS二极质谱，选择反应监测(SRM)方式进行检测。LXT-101的线性范围为0.5～500.0 ng·mL^-1(r²>0.993 0)，绝对回收率为85.2%～90.7%，日内、日间精密度(RSD%)均小于10.9%，准确度(RE)在±1.8%之内。血浆中的最低检测限(LOQ)为0.5 ng·mL^-1。该法操作简便、快速、灵敏度高。可检测出低剂量肌注(im)给药后犬体内的血药浓度，适于临床前药代动力学研究。     

Use of zolpidem 10 mg as a benzodiazepine substitute in 84 patients with insomnia

The antagonistic effects of zolpidem 10 mg on withdrawal symptoms caused by abrupt or gradual discontinuation (half-dose over 4 nights) of triazolam 0·25 mg in patients with chronic insomnia, who had been receiving regular treatment for over one month, were assessed in a randomized, double-blind, placebo-controlled clinical trial in general practice. Eighty-four patients were enrolled, mostly women (67·9%), with a mean age of 54·3±11·0 years. Twenty-one different general practitioners were solicitated for the recruitment. The subjects were randomized into four groups, and all received triazolam 0·25 mg during the run-in phase from day 1 (D1) to day 3 (D3). The following treatments were given from D4 to D7: triazolam 0·125 mg+zolpidem 10 mg (Group 1); zolpidem 10 mg (Group 2); placebo (Group 3); or triazolam 0·125 mg+placebo (Group 4). Groups 1 and 2 received zolpidem 10 mg from D7 to D24, while Groups 3 and 4 received placebo. Finally, all four groups received placebo (blind withdrawal phase) from D25 to D28. The following assessment criteria were used: clinical global impression (CGI) scale completed by the practitioner; patient questionnaire based on routine sleep criteria, wakefulness and daytime alertness. Secondary criteria were sleep diaries and visual analogue scales. Study drop-outs were reported and explained. The effectiveness/tolerance ratio was found to be statistically significant using the CGI (p<0·007) in favour of zolpidem 10 mg. There was no significant difference in patients subjective assessment between the groups except for nightmares (p<0·04) less frequent in patients receiving zolpidem. Zolpidem was found to be more effective than placebo at D21 (CGI) according to sleep diaries; the zolpidem group showed a statistically significant difference as compared to the three other concerning four sleep parameters: number of awakenings, anxiety, sleep duration, energy. Drop-out rates were significantly lower in the zolpidem group than in other ones (p<0·01). Abrupt and gradual triazolam withdrawal over 4 nights induced withdrawal symptoms. Equally no specific phenomena were observed at the end of the trial during the blind withdrawal phase. This study shows that zolpidem 10 mg improves sleep quality and reduces withdrawal symptoms after abrupt or gradual discontinuation of triazolam 0·25 mg in chronic patients with chronic insomnia. Copyright © 1998 John Wiley & Sons, Ltd.     

Possible differences in α-adrenoceptors in rabbit ileum and spleen

In isolated tissues from reserpinized rabbits (5 mg kg^?1, i.m. 20 h before experiment) and in the presence of cocaine (3 × 10^?5 m ), corticosterone (2·8 × 10^?5 m ), tropolone (3 × 10^?5m ), propranolol (4 × 10^?6m ) and disodium EDTA (3 × 10^?5m ), the potency ratios (relative to (—)-noradrenaline) of (—)adrenaline, (—)-phenylephrine and (±)-methoxamine were (m ± s.e.) 203 ±0·13, 0·045 ± 0·003 and 0·0062 ± 0·0018 respectively in splenic strips and 1·77 ± 0·41, 0·093 ± 0·018 and 0·029 ± 0·004 respectively in isolated ileum. Although the pA₂ values for phentolamine and thymoxamine against (—)-noradrenaline in the two tissues were very similar there was a statistically significant difference when using yohimbine as the α-adrenoceptor blocking agent (pA₂ = 6·80 ± 0·30 in spleen; 5·60 ± 0·12 in ileum). These differences suggest that the α-adrenoceptor in the two tissues is not identical. The pA₂ value of phentolamine in rabbit ileum was not significantly different whether (—)-noradrenaline or (±)-methoxamine was used as agonist (7·91 ± 0·07 and 7·97 ± 0·06 respectively) while that of yohimbine was 5·56 ± 0·10 using (—)-noradrenaline and 6·19 ± 0·12 using (±)-methoxamine. In the light of this latter result and, considering the scatter of the experimentally determined values, there may be two α-adrenoceptors in rabbit ileum and either or both may not be identical in all respects to the α-adrenoceptor found in rabbit spleen.     

The tetrahydrocannabinol and tetrahydrocannabinolic acid content of cannabis products

Cannabinoid acids readily decarboxylate to the corresponding cannabinoid. Methods are available for the determination of Δ⁹-tetrahydrocannabinol (THC) and its acids (THCA) and published data on the levels of these compounds in cannabis are summarized. Using gas and liquid chromatography, fresh cannabis (64 samples) and cannabis resin (26 samples) from different countries were examined. Wide variations in the relative amounts of THCA and THC in cannabis were found. For cannabis resin, a wide range of values was also found (0·5: 1 to 6·1: 1), the lower values being in resins from the Indian sub-continent and the higher values in resins from the Mediterranean area. Total THC values were in the range 1·–10·6% in cannabis and 6·0–12·5% in cannabis resin.     

乙醇对苯妥英钠药代动力学的影响

目的 :观察乙醇对苯妥英钠药代动力学的影响。方法 :分别对8只家兔单用苯妥英钠和乙醇合用后苯妥英钠的药代动力学参数变化进行研究和比较 ,采用紫外分光光度法测定苯妥英钠的经 -时血药浓度 ,以“3p87”程序拟合药代动力学参数。结果 :合用乙醇后 ,苯妥英钠的AUC由 (4108 64±1039 98)ml/(L·min)降至 (1903 65±1003 40)mg/(L·min) ;T1/2(ke)由 (98 45±26 4)min降至 (82 84±25 5)min ;Vd 由 (0 3475±0 0360)L/kg升至 (0 6819±0 1901)L/kg ;CLs 由 (0 0026±0 0008)ml/(kg·min)升至(0 0062±0 0022)ml/(kg·min) ;Cmax 由 (29 0±2 94)mg/L降至 (16 0±5 9)mg/L。结论 :合用乙醇后 ,苯妥英钠的消除在体内明显加快     

磷酸苯丙哌林缓释片人体生物利用度试验

目的 :比较磷酸苯丙哌林缓释片与咳快好普通片单剂与多剂双交叉试验的生物等效性、缓释片特殊释放特点以及体外释放与体内吸收间的相关性。方法 :采用高效液相色谱法测定磷酸苯丙哌林血药浓度 ,计算药代动力学参数和磷酸苯丙哌林的相对生物利用度。结果 :单剂口服磷酸苯丙哌林和咳快好T1/2( β) 分别为 (11 99±1 15)h、(11 91±1 41)h ,Tpeak分别为 (3 80±0 42)h、(2 25±0 26)h ,Cmax 分别为 (0 2787±0 03) μg/ml、(0 4507±0 07) μg/ml,AUC0～48 分别为 (4 1445±0 48) μg/(ml·h)、(3 8981±0 54) μg/(ml·h) ,AUC0～∞分别为 (4 7908±0 42) μg/(ml·h)、(4 3278±0 55) μg/(ml·h) ,磷酸苯丙哌林相对生物利用度为(112 40±0 06) %。多剂口服磷酸苯丙哌林和咳快好T1/2( β) 分别为 (11 68±1 24)h、(10 83±1 01)h ,Tpeak分别为 (3 10±0 32)h、(1 95±0 16)h ,Cmax 分别为 (0 4737±0 32) μg/ml、(0 6163±0 42) μg/ml ,AUC0～48 分别为 (9 3954±0 80) μg/(ml·h)、(8 5223±0 76) μg/(ml·h) ,AUC0～∞分别为 (10 1336±0 87) μg/(ml·h)、(8 8821±0 77) μg/(ml·h) ,波动系数分别为(48 32±16 80) %、(83 10±11 24) %。磷酸苯丙哌林体外释放度和体内吸收分数间相关吸收为0 992     

Emulsified Perfluorochemicals as Respiratory Gas Carriers: Recovery of Perfluorodecalin Emulsion Droplets from Rat Tissues

Abstract— To further understand the in-vivo biokinetic behaviour of perfluorochemical (PFC) emulsions, male rats were injected (10 mL kg^?1) with 30% (w/v) emulsified perfluorodecalin (FDC) and uptake into tissues assessed. At 72 h after injection, the mean (±s.e.m.) diameters of FDC droplets recovered from liver and spleen were 2·24 ± 0·04 and 2·78 ±0·10 μm, respectively; droplets recovered from lung after 72 h (mean: 1·73 ±0·13 μm) were significantly smaller (p < 0·01). After 7 days, FDC droplet diameters in liver had increased to 3·31 ± 0·13 μm (P < 0·01) and those in lung to 2·71 ± 0·14 μm (P < 0·01); droplets in spleen after 7 days (2·22 ± 0·09 μm) were similar to those at 72 h. These data support the hypothesis that significant initial coalescence of FDC droplets occurs in the rat liver and spleen, with further coalescence in the liver up to 7 days. The mean percentage of the injected FDC dose recovered from the liver after 72 h was 2·2 ± 0·4%, and after 7 days was 0·07 + 0·05% (P < 0·01). A smaller decrease in the percent injected FDC in spleen also occurred over the same period (72 h: 1·9 ± 0·3%; 7 days: 0·8 ± 0·5%; P < 0·01). The percent injected FDC in lung was similar at 72 h (0·007 ± 0·004%) and 7 days (0·005 ±0·001 %). FDC was undetectable (< 0·001 %) in all blood samples. The greater rate of FDC elimination from the liver than from the spleen may be related to differences in the rates of reticuloendothelial system processing between these organs.     

NASAL ADMINISTRATION OF MORPHINE-6-GLUCURONIDE IN SHEEP—A PHARMACOKINETIC STUDY

The pharmacokinetics of morphine-6-glucuronide (M6G) after both intravenous dosing and nasal administration were studied in sheep. The nasal formulation consisted of M6G in combination with an absorption promoting delivery system in the form of chitosan. The mean half-life of M6G after intravenous administration was 51·0±8·2 min and that after intranasal dosing was 45·0±5·5 min. M6G clearance and volume of distribution were 5·4±1·5 mL min^±1 kg^±1 and 0·4±0·1 L kg^±1 respectively. The plasma profile after nasal administration demonstrated rapid absorption of M6G. The bioavailability of M6G in the chitosan formulation was found to be 31·4%. These results suggest that M6G administered in combination with the chitosan delivery system may be considered as a suitable non-parenteral means of administering this analgesic.     

精氨酸布洛芬糖浆与布洛芬片剂人体药动学及生物等效性比较

目的:比较精氨酸布洛芬糖浆与布洛芬片在健康人体中的药动学及生物等效性。方法:采用液相色谱法测定18位健康男性受试者交叉服用精氨酸布洛芬糖浆和布洛芬片后的血浆中布洛芬浓度。结果:糖浆剂的药动学参数为:AUC_(0-10)=(150±s 17)mg·h·L~(-1),C_(max)=(47±9)mg·L~(-1),t_(max)=(0．6±0．3)h;布洛芬片剂的药动学参数为:AUC_(0-10)=(136±13)mg·L~(-1),c_(max)=(28±4)mg·L~(-1),t_(max)=(2．7±1．0)h,相对生物利用度为 (98±7)％。结论:精氨酸布洛芬糖浆和布洛芬片生物等效。     

In-vitro studies of enteric coated diclofenac sodium-carboxymethylcellulose microspheres

Abstract

Microspheres containing diclofenac sodium (DS) were prepared using carboxy-methylcellulose (CMC) as the main support material (1·0, 2·0, 3·0% (w/v)) and aluminium chloride as the crosslinker. Drug to polymer ratios of 1:1, 1:2 and 1:4 were used to obtain a range of microspheres. The microspheres were then coated with an enteric coating material, Eudragit®S-100, with aqueous solution concentrations of 10 and 20% (w/v). Encapsulation efficiency, % yield value, particle sizes and in-vitro dissolution behaviour were investigated. The surface of the enteric coated microspheres seemed to be all covered with Eudragit®S-100 from scanning electron microscopy observation. It was also observed that increasing the CMC concentration led to an increase in the encapsulation efficiency, % yield value and particle size and decreased the release rate. Eudragit®S-100 coating did not significantly alter the size but the release rate was significantly lower even when the lower concentration solution was used.     

Biochemical pharmacology and toxicology of 8-azaadenosine alone and in combination with 2′-deoxycoformycin(pentostatin)

The toxicology and metabolism of 8-azaadenosine (8-azaAdo) were examined both as a single agent and in combination with the adenosine deaminase inhibitor, 2′-deoxycoformycin (dCF). The LD₁₀ (mice) for 8-azaAdo alone on a once daily for 5 days (q.d. × 5) schedule was 30mg·kg^?1·day^?1. When the animals were pretreated with 0.1 mg·kg^?1·day^?1 of dCF, the ld₁₀ dose was reduced to 10 mg·kg^?1·day^?1× 5. The major organ toxicity seen was hepatic. Bone marrow cellularity was only slightly altered at the ld₁₀ dose. 8-AzaAdo nucleotides were detected in the livers of treated mice as determined by high performance liquid chromatography. Further, after 2 hr of incubation, isolated rat hepatocytes accumulated 8-azaATP to levels of 2.2 μmoles/g of cells with 8-azaAdo (1 mM) alone and to 4.3 μmoles/g of cells when 8-azaAdo was used in combination with dCF (1 μg/ml). ATP levels decreased to below the limits of detection after 2 hr in cells treated with the combination. The replacement of cellular ATP by 8-azaATP may provide an explanation for the hepatotoxicity observed in the murine toxicology studies.     

Endothelium-dependent Relaxation in Response to Ethanol in the Porcine Isolated Pulmonary Artery

Many drugs cannot be dissolved in distilled water and so other solvents such as ethanol, dimethylsulphoxide and methanol are used. Because very little is known about the direct effects of these three solvents on the cardiovascular system, we have examined their effects on isolated pulmonary and coronary arteries from the pig. Increasing concentrations of ethanol, dimethylsulphoxide and methanol induced relaxation in porcine pulmonary (at 1·2% v/v, 59·9±9·0% (n = 9), 55·9±9·0% (n = 6) and 12·3±6·4% (n = 8), respectively, of U46619-induced tone) and coronary arteries (at 1·2% v/v, 69·9±7·1% (n = 10), 78·9±6·1% (n = 7) and 12·9±8·2% (n = 6) respectively, of U46619-induced tone). In the pulmonary arteries the relaxation in response to ethanol was found to be endothelium-dependent whereas the responses to dimethylsulphoxide and methanol were unaffected by removal of the endothelium. In the coronary arteries the relaxation to all three solvents was independent of the presence of the endothelium. Comparison of the sensitivity of the tissues to the solvents showed that ethanol and dimethylsulphoxide produced comparative responses in both the pulmonary and coronary arteries, whereas methanol was much less potent. The endothelium-dependent response to ethanol in the porcine pulmonary artery (maximum response, E_max, 67·1±9·3% of U46619-induced tone, n = 7) was attenuated by the cyclooxygenase inhibitor, flurbiprofen (E_max 31·9±12·0%, n = 7), the nitric oxide synthase inhibitor, L-NAME (N^G-nitro-L-arginine methyl ester; E_max 23·5±10·2%, n = 7)) and the combination of both inhibitors (E_max 18·3±7·8%, n = 7). The residual relaxatory response to ethanol was abolished, and converted into a contractile response, both by removal of the endothelium (at 1·7% v/v ethanol 27·3±11·5% of U46619-induced tone, n = 7) and by the addition of a low concentration of KCl (49·9±10·3%, n = 6), suggesting the release of a non-prostanoid, non-nitric oxide factor from the endothelium. This response, however, was not attenuated by the cannabinoid receptor-antagonist SR141716A (N-(piperidin-1-yl)-5-(4-chloro-phenyl)-1-(2,4-dichlorophenyl)-4-methyl-1H-pyrazole-3-carboxamide HCl; 52·5±4·3% relaxation, n = 8), suggesting that the factor released in this preparation by ethanol is not a cannabinoid. The results of this study indicate that many solvents commonly used in pharmacological experiments have pronounced vasoactive properties. Methanol might be the vehicle of choice, because it was the least active solvent, whereas high concentrations of ethanol might influence vascular function at both the level of the smooth muscle and the endothelium, with the action on the endothelium involving the release of endothelium-derived relaxing factors.     

HPLC-MS/MS法测定大鼠血浆中的知母皂苷B-Ⅱ

目的建立快速、灵敏和准确的大鼠血浆中知母皂苷B-Ⅱ液质联用(HPLC-MS/MS)定量分析方法。方法大鼠血浆样品用乙腈沉淀蛋白,上清液经Alltima HP C18柱(2.1mm×50mm,5μm)分离,采用负离子检测多反应监测模式(MRM)、电喷雾离子化(ESI)对知母皂苷B-Ⅱ进行定量分析,内标为ParisaponinⅠ(重楼皂苷Ⅰ)。检测离子对为知母皂苷B-Ⅱ离子对(m/z919.4→757.4)与"重楼皂苷Ⅰ"离子对(m/z1033.5→901.4)。结果方法的线性范围为5～2000μg·L-1,最低定量下限5μg·L-1。日内精密度<10.9%,日间精密度<6.6%,准确度为-8.6%～7.5%;每样品分析时间为3min。结论该法准确、灵敏、特异,适用于血浆中知母皂苷B-Ⅱ的测定。     

膦甲酸钠干预高磷诱导的血管平滑肌细胞钙化的研究

目的　观察不同浓度的膦甲酸钠 (PFA)对高磷诱导的牛主动脉血管平滑肌细胞钙沉积和骨钙素 (OC)表达的影响。方法　用不同磷浓度 (正常磷Pi1.5mmol·L-1、高磷Pi2 0mmol·L-1)及含不同浓度膦甲酸钠的培养液 ,体外培养牛主动脉平滑肌细胞 ,观察血管平滑肌细胞钙沉积及骨钙素表达。用甲ο 酚酞络合酮方法测定钙含量 ,BCA法测定蛋白含量。培养上清液中骨钙素浓度用放射免疫法测定 ,用蛋白含量标化钙含量、骨钙素的浓度 ,RT PCR观察骨钙素mR NA的表达。结果　①高磷组较正常磷组平滑肌细胞钙沉积增加 :细胞培养 6d后 ,高磷组 (77 187± 11 6 92 )mg·g-1Pro ,正常磷组 (2 5 76 8± 1 75 0 )mg·g-1Pro ,P <0 0 1;②膦甲酸钠能有效地抑制钙沉积 :培养 6d ,高磷 +PFA 1 0mmol·L-1组 (37 72 9± 5 899)mg·g-1Pro ,与高磷未干预组相比 ,P <0 0 1;③高磷组骨钙素表达明显增高。高磷组与正常磷组相比 ,培养上清液中骨钙素水平 :(1 5 0 3× 10 -2 ±2 6 0 1× 10 -3 )mg·g-1Pro对 (2 981× 10 -3 ± 8 382× 10 -4)mg·g-1Pro ,P <0 0 1;平滑肌细胞骨钙素mRNA表达 (OC/GAPDH) :1 886± 0 16 5对 0 75 2± 0 0 5 2 1,P <0 0 1;④膦甲酸钠能有效地抑制骨钙素的表达。高磷 +PFA 1 0mmol·L-1组与高磷组?     

复方盐酸曲马多人体药动学研究

目的:研究复方盐酸曲马多的人体药动学。方法:10名健康志愿者口服复方盐酸曲马多1片(每片含盐酸曲马多37.5mg,对乙酰氨基酚325mg),用高效液相色谱-荧光法测定血浆中曲马多的浓度,计算药动学参数。结果:口服复方盐酸曲马多片1片后AUC0~24为(1361.61±441.79)ng·h·mL-1,AUC0~∞为(1555.04±582.51)ng.·h·mL-1,Cmax为(134.81±33.96)ng·mL-1,tmax为(1.9±0.57)h,t1/2为(7.63±2.02)h。结论:本方法可用于复方盐酸曲马多人体药动学研究。     

Micro-colorimetric determination of adenosinetriphosphatase activity in freeze-dried sections of rat diaphragm muscle

A technique is described for determination of ATPase activity in 3–30 μg samples dissected from freeze-dried sections of rat diaphragm muscle. Tissue samples are incubated at room temperature with optimal concentrations of ATP (10 mM) and MgSO₄ (5 mM) in 0·1 M tris/HCl buffer at pH 7·4. Inorganic phosphate is measured spectrophotometrically. Mean activity for 20 rats was 0·22 ± 0·06 (s.d.) mole-Pi/kg/wet tissue/15 min. Results did not depend on plane of section or section thickness. 5 mM Mg²⁺, 10 mM Ca²⁺ and 1 mM 2, 4-dinitrophenol produced maximal ATPase activation and inhibition was obtained with p-chloromercuribenzoic acid (pI₅₀3·9) but not chlorpromazine (0·01–0·1 mM). There was no significant evidence of Na⁺ plus K⁺ activated ATPase or inhibition with ouabain (5 mM). ATPase activity was uncharacterized and relative contributions of specified muscle ATPase systems were unknown. As an insoluble enzyme system was involved and photomicrographs showed characteristic muscle features in freeze-dried sections, ATPase activity appeared due to enzymic function in situ. Results are discussed in relation to mutual availability of enzymic sites and reagents.     

2种奥美拉唑肠溶胶囊的人体生物等效性研究

目的研究2种奥美拉唑肠溶胶囊的生物等效性。方法20名健康男性志愿者随机分成2组,交叉口服受试制剂和参比制剂各40mg,采用高效液相色谱法测定人血清中奥美拉唑浓度,由DAS软件计算药动学参数及相对生物利用度。结果受试制剂与参比制剂的t1/2分别为(1.685±0.866)、(1.653±0.862)h,tmax分别为(2.425±0.693)、(2.200±0.865)h,Cmax分别为(0.894±0.481)、(0.865±0.342)μg·mL-1,AUC0～10分别为(2.041±1.446)、(2.022±1.322)μg·h·mL-1,AUC0～∞分别为(2.163±1.594)、(2.125±1.507)μg·h·mL-1,受试制剂的相对生物利用度为(100.3±17.4)%。结论2种奥美拉唑肠溶胶囊具有生物等效性。