A method for calculating the mean absorption time of drugs undergoing reversible and first-pass metabolism

A method has been derived for calculating the mean absorption time of an oral drug and its interconversion metabolite which is generated from the drug systemically and presystemically. The method evolves from the convolution integral and requires plasma AUC and AUMC values after separate intravenous administration of the drug and its interconversion metabolite and oral administration of the drug. It can also be used to calculate the mean input time of a drug undergoing reversible metabolism and administered by any other extravascular route. Results of a simulation study using both errorless and errant data indicate that, when the absorption rate constant of a drug or its interconversion metabolite is not much larger than the apparent elimination rate constant, the proposed method performs satisfactorily. However, when the absorption rate constant of a drug or its interconversion metabolite is much larger than the apparent elimination rate constant, the proposed method appears to be inaccurate.     

Mechanisms of tolerance during treatment with nitroglycerin patches for 24 h

Objective: We examined the relationship between tolerance development, counterregulatory responses and arterial vasodilating effects evaluated by digital pulse plethysmography. Methods: Twenty patients with stable angina pectoris were exercise tested before, after 2 and after 24 h of open nitrate patch treatment. Results: The effects observed after 2 h of treatment on exercise duration, ST-segment depression, blood pressure and heart rate were lost in most individuals after 24 h. In contrast, the effects on the arterial pulse curves persisted after 24 h, with a mean change from baseline of 29%, compared to 33% at 2 h. After 24 h, a significant decrease in haematocrit and an increase in body weight were observed. The haematocrit changes correlated with the loss of clinical efficacy (r =0.57 for ST-segment depression, and r =0.54 for exercise duration). Conclusion: Clinical nitrate tolerance may be observed despite maintenance of the arterial vasodilating effects, and tolerance is more related to plasma volume expansion as a counterregulatory mechanism. Received: 28 February 1996/Accepted in revised form: 5 July 1996     

用化学发光自显影技术快速检测鸭沙门氏菌

应用我室建立的化学发光自显影技术检测鸭沙门氏菌。用酶标抗体与硝酸纤维素膜上固定的细菌结合,再同发光底物溶液作用,使X线胶片感光,根据胶片上的黑斑进行半定量,可检出100个菌。其检测特异性好,约2小时即可出报告。     

A Novel Extravascular Input Function for the Assessment of Drug Absorption in Bioavailability Studies

Purpose. Flexible parametric models describing the input process after extravascular drug administration are needed for the assessment of absorption rate and the use of population methods in bioavailability and bioequivalence studies. Methods. The oral concentration-time curve modeled as the product of the input and disposition function in the Laplace domain was obtained by numerical inversion methods for parameter estimation. The utility of the inverse Gaussian input density was examined using bioavailability data of an extended-release dosage form. Measures of rate of absorption and the cumulative absorbed amount profile were defined in terms of the estimated model parameters. Results. Accurate estimation of absorption parameters was achieved by simultaneous fitting of the extravascular and intravascular data (describing the latter by a triexponential function). The new input function allowed a direct estimation of both extent of absorption and mean absorption time. Conclusions. The findings suggest that the inverse Gaussian density is a useful input function. Its flexibility may reduce the effect of model misspecification in parameter estimation. All parameters can be readily interpreted in terms of the absorption process.     

双氯灭痛药膜体外透皮速率的实验研究

作者选择乙基纤维素、聚乙烯醇等高分子材料制成涂膜剂，用大鼠皮进行双氯灭痛药膜的体外透皮速率测定。结果表明，氮酮与丙二醇可以促进药物渗透。不同的高分子材料可影响药物的扩散与释放，从而影响其透皮速率。与无膜无促透剂处方相比，药物在乙基纤维素中的透皮速率没有增加，在聚乙烯醇膜中的透皮速率有显著增加。     

免疫反应在实验性游离型腰椎间盘突出自然吸收中的意义

目的：通过检测CD3和IgG在实验性游离型腰椎间盘突出自然吸收中的表达，探讨腰椎间盘突出后能否自然吸收及其可能的吸收机制。方法：将25只成年狗平均分成5组，从L2/3切取髓核组织，置于L5处的硬脊膜外，于术后2，4，6，8，12周，取动物标本以及正常部位的髓核组织，用CD3抗体和抗IgG进行免疫组化检测。结果：约30%的标本局部为脂肪组织，54%的标本局部硬脊膜与骨粘连，16%的标本既无粘连也无脂肪，免疫组化测定显示，随着时间的推移，CD3^ 细胞的浸润程度呈递减趋势，而IgG沉积的分布程度呈递增趋势，正常髓核无CD3^ 细胞浸润，IgG沉积分布极少。结论：在椎管内，狗游离的髓核组织8-12周后可部分或全部自然吸收，其吸收机制是机体自身免疫反应的结果。     

Small-dose oral iron absorption test in anaemic and non-anaemic elderly hospitalized patients

Abstract: The small-dose (20 mg) oral iron absorption test (OIAT) was performed in 76 hospitalized elderly patients and 30 healthy adults. Of the elderly patients, 34 were considered as iron deficient (serum ferritin level <20 μg/L) of whom 23 were anaemic and 11 not anaemic, 21 had the anaemia of chronic disorders (ACD) and another 21 were non-anaemic patients with a normal serum ferritin level. There was a significant inverse correlation between the serum ferritin level as a measure of iron store and the maximum increase in serum iron during a 3-h test (C_max), in the elderly as well as in the healthy adult group. A decision limit of 80 μg/dL for C_max is a good discriminant between absent (serum ferritin <20 μg/L) and adequate body iron stores. Sixty-eight per cent of the patients with a serum ferritin level <20 μg/L but virtually none of the ACD patients, non-anaemic elderly inpatients with normal serum ferritin levels and healthy adults had a C_max level >80 μg/L. Although further investigation is needed before the OIAT can be recommended as a valuable test for evaluating iron absorption, predicting mild iron deficiency and differentiating between different categories of anaemia, it seems worthwile that more effort should be done to validate this simple and safe test.     

Plasma concentrations and bioavailability of propranolol by oral, rectal, and intravenous administration in man

Eight normal male volunteers received 80 mg doses of propranolol by the oral and rectal routes and 2.2 mg by intravenous administration in a crossover fashion. Plasma concentrations of propranolol were measured by a gas chromatographic method using an electron capture detector. Individual subject concentration-time data were analysed and results indicated that the data fit a two compartment model with first order absorption. An approximately two-fold higher plasma propranolol concentration was observed after rectal administration as compared with oral dosing. Statistical analysis of the difference in the total AUCs indicates a significantly higher bioavailability of propranolol administered by the rectal route. The reduced bioavailability after oral administration indicates a substantial first pass effect but that it is possible to bypass the liver, at least partially, by giving the drug rectally to man.     

马蹄莲不同部位微量元素的含量测定

目的 探讨马蹄莲不同部位微量元素的含量。方法 用发射光谱法、原子吸收法测定了马蹄莲根、茎、叶中20种微量元素的含量。结果 马蹄莲根、茎、叶中含有12种人体必需微量元素，其中Fe、Mn、Zn、Si、Li、Ca等七种元素含量较高。结论 马蹄莲富含多种人体必需的微量元素，预示马蹄莲具很高的药理保健价值。