铊在大鼠体内的吸收,分布和排泄

以碳酸亚铊１０ｍｇ／ｋｇ经口给大鼠灌胃染毒，，５分钟后，可在大部份组织中测到铊，半小时，除胃以外，肝中含量最高；１小时后，除胃以外，脾和肾中含量最高，次为心和睾丸；２小时肾中浓度居首位，其高峰期在４－８小时，４小时后，骨中含量增高，仅次于胃，脑，肌肉。     

银蒿中7种微量元素含量分析

用火焰原子吸收法测定了银蒿中 7种微量元素的含量 ,结果表明银蒿中Ca的含量最高 ,Zn、Na、Fe的含量次之 ,为银蒿的进一步开发利用提供科学依据。     

Effects of a new lipid-based drug delivery system on the absorption of low molecular weight heparin (Fragmin) through monolayers of human intestinal epithelial Caco-2 cells and after rectal administration to rabbits

The effects of a novel drug delivery system, consisting of a lipid matrix and a drug, on the permeability, morphology and drug transport across monolayers of human intestinal epithelial cells were investigated. A 1:3 mixture (w/w) of chromatographically purified soybean phosphatidylcholine and medium chain monoacylglycerol was chosen as lipid matrix (PC:MG) and mannitol (mol. wt. 182) and Fragmin (low molecular weight heparin; mean mol. wt. 5000) were chosen as hydrophilic model drugs. PC:MG had an immediate and dose-dependent effect on the permeability of the cell monolayers, and on epithelial morphology (as seen under transmission electron microscopy). PC:MG (4–10 mM) dose-dependently enhanced the transport rate of mannitol and Fragmin, causing an approximately 10-fold increase in the transport rate of Fragmin at concentrations of 6–8 mM. The increase was independent of the dose of Fragmin and was reversible in concentrations up to 6 mM. At higher doses, clear effects on the apical cell membranes were observed although the tight junctions remained intact. PC:MG also enhanced Fragmin absorption in vivo after rectal administration to New Zealand White rabbits. Co-administration of Fragmin with PC:MG (7 mM) resulted in an increase in the relative bioavailability (compared with s.c. administration) from < 1% (without PC:MG) to 21 ± 12%. A maximal increase in relative bioavailability to 90 ± 19% was obtained at a PC:MG concentration of 35 mM. Thus, PC:MG functions as an absorption enhancer both in the cell monolayer model and in vivo, in the same concentration range. The results indicate that as well as providing mechanistic information, studies of absorption enhancers in Caco-2 monolayers also provide information on suitable dosage regimens for in vivo studies.     

The application of partial areas in assessment of rate and extent of absorption in bioequivalence studies of conventional release products: experimental evidence

A bioequivalence study on perphenazine/amitriptyline combination compared three formulations (TST-1, TST-2 and REF) containing the same nominal dose of perphenazine, while TST-2 contained 20% less amitriptyline than the other two formulations. ANOVA-SNK on log-transformed partial areas AUC₀²⁴ through AUC₀^∞ showed the intra-subject variabilities of perphenazine to be consistently higher than those of amitriptyline or nortriptyline. There was also a marked increase in intra-subject variability for perphenazine on extrapolating AUC₀^last to infinity. Thus, whhile the 1–2 confidence intervals (90% CIs) and ratios of geometric means for perphenazine fell within preset limits of 80–125% in all pairwise comparisons, the CIs for AUC₀^∞ violated the upper limit in comparisons of TST-2 and REF (or TST-2 and TST-1). This outcome could be attributed to high intra-subject variability on AUC₀^∞. ANOVA-SNK of amitriptyline identified a significant difference in extent of amitriptyline absorbed from TST-2 compared with TST-1 and REF. Thus, in pairwise comparisons between TST-1 and REF, all 90% CIs for amitriptyline partial areas AUC₀⁴ through AUC₀^∞ fell within 80–125% limits. In corresponding comparisons between TST-2 and REF (or TST-2 and TST-1), however, the lower limit of the 90% CIs for AUC₀¹ through AUC₀^last consistently fell below the 80% cut off. By contrast, 90% CIs associated with the ratios C_max/AUC₀⁴ through C_max/AUC₀^∞ all fell within preset limits indicating no differences in absorption rate of amitriptyline, consistent with the theoretical argument that C_max/AUC is influenced by rate but not extent of absorption. Thus the partial area method is applicable to the evaluation of both relative rate and extent of absorption from conventional release products. Similarly, analyses of nortriptyline data showed that the partial area method is also effective in the evaluation of rate and extent of formation of a metabolite in a bioequivalence study. The partial area method permits a greater number of plasma samples to be devoted to accurate estimation of t_max and C_max since the necessity to estimate AUC₀^∞ is obviated.     

Bovine ferritin iron bioavailability in man

The bioavailability of ferritin iron was evaluated in human subjects using radiolabelled [⁵⁵Fe]ferritin isolated from bovine spleen and liver. Preliminary studies with bovine spleen ferritin labelled in vitro demonstrated an inappropriately high absorption compared with ferritin labelled in vivo , and the latter was therefore used in all subsequent absorption studies. In 10 subjects, geometric mean absorption from 5 mg of ferritin iron was 3.8% when taken without and 3.2% when taken with food ( P  >0.05). These values were significantly lower than absorption from the same dose of iron given as ferrous sulphate, which averaged 24.1% without and 8.2% with food. When the iron dose was increased 10-fold, absorption of ferritin iron averaged only 0.6–0.7% with or without food as compared with 7.9% without and 2.6% with food when the iron was given as ferrous sulphate. In a further study, mean absorption from bovine spleen ferritin of 4.0% did not differ significantly from the mean of 2.7% observed with bovine liver ferritin. These findings confirm previous studies indicating that ferritin iron is poorly absorbed. Furthermore, its use as a pharmaceutical iron preparation cannot be advocated.     

Decreased ciprofloxacin absorption with concomitant administration of ferrous fumarate

The effect of ferrous fumarate on the relative bioavailability of ciprofloxacin after a single 500 mg oral dose of ciprofloxacin was studied in eight healthy males. Blood samples were collected at regular intervals 0–24 h post-dose. Urine was collected during 24 h to determine the cumulative urine excretion of ciprofloxacin. Ciprofloxacin concentrations in serum and urine were determined by high pressure liquid chromatography. Mean area under the serum concentration—time curve decreased significantly (P<0.001) after ciprofloxacin was taken with 200 mg ferrous fumarate. The relative bioavailability was 30% when ciprofloxacin was given with ferrous fumarate. The maximum blood level decreased from 2.1±0.9 (control) to 0.6±0.2 mg/l (with ferrous fumarate). Further studies are needed to determine if chronic treatment with ferrous fumarate further decreases the relative bioavailability. For the moment administration of ciprofloxacin with ferrous fumarate should therefore be avoided.     

中国人食入232Th的胃肠道吸收分数

目的 估算中国人食入^232Th的胃肠道吸收分数。方法 按文献介绍f1计算方法和近年所获我国成年男子膳食食品和器官组织中钍浓度研究结果，计算并比较采用浓度算术均值和中位数所获的f1结果。结果 按全国中位数和算术均值估算出的^232Th f1分别为0．00048和0．00028。结论 我国成年男子膳食摄入^232Th的f1应采用0．00048，该结果低于按UNSCEAR最新世界参考值估算的结果，但接近于亚洲国家印度或日本相应报道值和支持ICRP对膳食钍f1的最新推荐值0．0005。     

ELECTRICAL POLARIZATION OF RECTAL MUCOSA and EXCRETION OF TETRAHYDROALDOSTERONE IN PATIENTS WITH CYSTIC FIBROSIS OF PANCREAS and IN NORMAL SUBJECTS

Abstract. Rask-Madsen, J., Schiøtz, P. O., Bartels, U., Nielsen, M. D. and Becher-Christensen, F. Medical Department F and the Department of Clinical Physiology, Glostrup Hospital, Glostrup, and the Department of Pediatrics TG, Rigshospitalet, Copenhagen, Denmark). Electrical polarization of rectal mucosa and excretion of tetrahydro-aldosterone in patients with cystic fibrosis of pancreas and in normal subjects. Acta Paediatr Scand, 64:81, 1975.–The electrical potential difference (PD) across the rectal wall was measured in 26 patients with cystic fibrosis of pancreas (CFP) and in 18 healthy subjects. The PDs obtained in normal children were identical to those previously obtained in normal adults. A significantly greater dispersion of the values was observed in CFP. When the patients were divided into groups according to metachromasia in fibroblast cultures, the mean PD was increased only in the ametachromatic group. True enough, this observation suggests a difference between various forms of CFP, distinguished by metachromasia, and thus is a further indication of the heterogeneity of the disease. The greater abnormalities in metachromasia negative patients may, however, be due solely to the fact that these patients are more severely affected by the disease. The urinary excretion of tetrahydroaldosterone in patients was within the ranges obtained in controls, which excludes the possibility of secondary hyperaldosteronism as the source of increased PD. No evidence was provided in favour of a basic defect in the intestinal transport of Na⁺ or CI⁻, but K⁺ concentrations in faecal fluids of patients were significantly lower than in controls. The equilibrium concentration of K⁺ could be accounted for by simple passive diffusion, suggesting that the epithelium behaved inertly with respect to this ion in CFP.     

用平均吸收率计算吸收速率常数

本文介绍利用平均吸收率替代待吸收百分率计算血管外途径给药后的药物吸收速率常数(K_α)。结果与电子数字计算机用非线性最小二乘法及文献数据复算的结果均一致。而且,用本法受观察终点对计算结果K_α的影响甚小。