Effect of iron deficiency anaemia and its treatment on sulphadimidine absorption

Summary The effect of iron deficiency anaemia and its treatment on the absorption of sulphadimidine has been investigated in adult patients.The absorption judged by total % of the dose excreted in urine and C_max, t_max, AUC and Kabs in plasma, was not significantly different before and after iron therapy or correction of anaemia.However, sulphadimidine absorption by the anaemic patients was significantly greater than in normals.     

Iron deficiency anaemia and Helicobacter pylori infection

Iron deficiency anaemia (IDA) is the most common form of anaemia world-wide. IDA is the simple result of an imbalance between iron loss and absorption. Gastric function with hydrochloric and ascorbic acid is essential for iron absorption. Some strains of Helicobacter pylori are able to acquire iron, competing with the host. A large percentage of patients with atrophic body gastritis (ABG) develop IDA and 61% of them are H. pylori positive. Recent evidence suggests that H. pylori infection could cause IDA in the absence of peptic ulcer or other upper gastrointestinal (GI) tract bleeding lesions. Gastritis extending to the corpus and a high bacterial load are features of these patients. About 70% of IDA patients with ABG or H. pylori gastritis are premenopausal women. Both ABG and H. pylori gastritis should be considered when evaluating the GI tract of patients with iron deficiency anaemia.     

Pharmacokinetics of single and multiple doses of phenytoin in man

Summary Plasma concentration of phenytoin (diphenylhydantoin, DPH) have been studied in 5 volunteers after single oral and iv doses (5.0 mg sodium DPH/kg), and after multiple oral doses (2.0 mg sodium DPH/kg b.i.d. for 12 days). The data were analysed according to a one compartment model. The plasma half-life was 14.5 h±1.2 S.D. after i.v. administration, its apparent volume of distribution varied little (0.52 l/kg±0.04) and its bioavailability ranged between 0.70 and 1.0 (mean 0.87). After oral administration peak plasma concentrations were reached in 4 to 12 h. Elimination curves were slightly convex, probably due to an effect of slow absorption. Steady-state plasma levels varied twofold between individuals after multiple oral doses and exceeded those predicted from the single i.v. dose by 29 to 77%. The discrepancy was considered to be due to transition to dose-dependent kinetics.This is the last paper written in collaboration with Dr. Balzar Alexanderson before his untimely death on 2nd June 1973. We are grateful for the inspiring and fruitful experience of working with him. To honour his memory as a good friend and brilliant clinical pharmacologist a number of papers from our laboratory will be dedicated to him.     

Iron deficiency anaemia and Helicobacter pylori infection

Iron deficiency anaemia (IDA) is the most common form of anaemia world-wide. IDA is the simple result of an imbalance between iron loss and absorption. Gastric function with hydrochloric and ascorbic acid is essential for iron absorption. Some strains of Helicobacter pylori are able to acquire iron, competing with the host. A large percentage of patients with atrophic body gastritis (ABG) develop IDA and 61% of them are H. pylori positive. Recent evidence suggests that H. pylori infection could cause IDA in the absence of peptic ulcer or other upper gastrointestinal (GI) tract bleeding lesions. Gastritis extending to the corpus and a high bacterial load are features of these patients. About 70% of IDA patients with ABG or H. pylori gastritis are premenopausal women. Both ABG and H. pylori gastritis should be considered when evaluating the GI tract of patients with iron deficiency anaemia.     

小剂量间歇补铁法在小儿缺铁性贫血治疗中的疗效观察

目的研究小剂量间歇补铁法治疗小儿缺铁性贫血（IDA）的临床疗效及副作用。方法对138例缺铁性贫血患儿进行分组,小剂量组70例,常规剂量组68例,分别进行小剂量间歇补铁治疗及常规剂量每日补铁治疗,每周复查血红蛋白（Hb）,观察治疗效果。结果小剂量组与常规剂量组比较血红蛋白上升速度相同,差异无统计学意义（P〉0．05）,常规剂量组副作用发生率高于小剂量组,差异有统计学意义（P〈0．05）。结论小剂量间歇补铁法与常规剂量补铁法治疗小儿IDA疗效相同,且副反应发生率低、程度轻,认为小剂量补铁法较好,值得临床推广。     

The bioavailability and pharmacokinetics of glucosamine hydrochloride and chondroitin sulfate after oral and intravenous single dose administration in the horse

OBJECTIVE: The purpose of this study was to determine if glucosamine (GL) hydrochloride (FCHG49) and low molecular weight (LMW) chondroitin sulfate (CS) (TRH122) are absorbed after oral administration to horses. The bioavailability of LMWCS was evaluated by quantifying the total disaccharides found in the plasma following chondroitinase ABC digestion. METHODS: Two separate studies were conducted. In study 1, ten adult horses received the following four treatments in a randomized crossover fashion: (1) i.v. LMWCS (3 g of 8 kDa), (2) p.o. LMWCS (3 g of 8 kDa), (3) i.v. LMWCS (3 g of 16.9 kDa) and (4) p.o. LMWCS (3 g of 16.9 kDa). Each group received 9 g GL with LMWCS. In a second study, each horse (n=2) was randomly assigned to receive either i.v. administration of GL HCl (9 g) or p.o. administration of GL HCl (125 mg/kg). Blood samples were collected, assayed and pharmacokinetic parameters were determined. RESULTS: GL was absorbed after oral dosing with a mean C(max) of 10.6 (6.9) microg/ml and a mean T(max) of 2.0 (0.7) h. The extent of absorption of LMWCS after dosing with both the 8.0 and 16.9 kDa provides evidence that LMWCS is absorbed orally. C(max) and AUC were higher (p<0.05) for the 16.9 kDa material compared with 8.0 kDa. However, the 16.9 kDa bioavailability was less than 8.0 kDa, but this difference was not significant. CONCLUSIONS: This study provides the first report of the bioavailability of orally administered GL and LMWCS in the horse.     

蔗糖铁注射液治疗缺铁性贫血临床观察

目的：探讨静脉用蔗糖铁治疗缺铁性贫血（IDA）的有效性和安全性。方法：选择60例IDA患者。随机分为静脉组和口服药物组,观察两种方法对纠正缺铁、改善贫血的效果和不良反应。结果：治疗后两组患者血红蛋白（Hb）、铁蛋白（Fer）均较治疗前明显升高。静脉组Hb、Fer上升幅度明显高于口服组,差异显著。静脉组无明显不良反应,口服组有12例（20．00％）发生胃肠道反应。结论：静脉用蔗糖铁可作为IDA患者有效治疗方法,疗效优于口服铁剂,且不良反应发生率低。     

间隔补铁法在缺铁性贫血治疗中的临床效果

目的 探究间隔补铁法在缺铁性贫血治疗中的临床应用效果.方法 80例缺铁性贫血患者,采用随机数字表法分成对照组及观察组,各40例.对照组接受连续补铁法治疗,观察组接受间隔补铁法治疗.比较两组患者的临床疗效及不良反应发生情况.结果 观察组患者的总有效率为95.00％,高于对照组的77.50％,差异有统计学意义(P<0.05...     

两种布洛芬缓释制剂的药物动力学与相对生物利用度

目的：考察两种布洛芬缓释剂芬尼康止痛消炎片与芬必得胶囊达稳态后，血清中布洛芬的药物动力学与相对生物利用度。方法：采用反相高效液相色谱法分别测定１８名健康志愿受试者一日两次分别口服芬尼康６００ｍｇ与芬必得６００ｍｇ达稳态后，布洛芬的血药浓度变化情况，计算药物动力学参数与相对生物利用度，并以配对ｔ检验与双单侧ｔ检验进行统计分析。结果：两种制剂达稳态后Ｃｓｓｍａｘ分别为２６．６±５．６与２６．８±６．２ｍｇ·Ｌ－１，Ｔｍａｘ分别为２．８±０．５与２．７±０．６ｈ，ＡＵＣ０→∞分别为２９８．８±６５．７和２９８．８±７１．１（ｍｇ·Ｌ－１·ｈ），ＦＩ分别是１２３．７％±１９．５％与１２２．３％±２６．０％；以配对ｔ检验与双单侧ｔ检验对上述参数进行统计分析，两种制剂的Ｃｓｓｍａｘ、ＡＵＣ０→∞、Ｔｍａｘ、ＦＩ差异均无显著性（Ｐ＞０．０５）。结论：两者具生物等效性；以芬必得为标准参比制剂，芬尼康相对生物利用度为１０１．７％±１６．８％。     

Application of a simplified method to determine bioavailability of an oral dose of phenytoin

The bioavailability of capsules of phenytoin was determined by two methods: a method involving the numerical integration of the Michaelis-Menten equation and an alternative method involving fitting the time course of plasma concentrations, following the administration of the reference intravenous dosage, to an empirical quadratic function of time. The latter procedure requires much simpler computations. The two methods yielded very similar estimates of the rate and extent of absorption of phenytoin. Total absorption was 0.90±0.05 and 0.89±0.05(x±SE, n=6)using the methods of numerical integration and quadratic curve fitting, respectively. Both methods indicated that the rate of absorption of phenytoin was inconsistent and slow. Half the total absorption of phenytoin occurred over 2.5 ±0.3 hr but the remainder was absorbed very slowly over a period of about 30 hr. Empirical functions may be more generally useful in the determinations of the bioavalability of drugs, particularly if some aspects of the disposition are saturable.     

Effect of saliva flow rate on saliva phenytoin concentrations: implications for therapeutic monitoring

The effect of atropine-induced reductions in saliva flow rate on saliva phenytoin concentrations were evaluated in a randomised placebo-controlled crossover study in a group of epileptic patients stabilised on the drug.Pretreatment with atropine caused significant reductions in saliva flow rates during the first 4 h, compared to saline. The AUC_{0–4 h} for saliva flow rate was significantly reduced by atropine (245 g vs 327 g) and the saliva phenytoin AUC_{0–4 h} was significantly increased (5.6 g · ml^–1 · h vs 4.5 g · ml^–1 · h) without affecting plasma phenytoin concentrations. The saliva/plasma phenytoin AUC_{0–4 h} ratio was therefore significantly increased by atropine (0.15 vs 0.12). However, there was a poor correlation between saliva/plasma phenytoin concentration ratios and saliva flow rates for the two treatments in the individual patients (correlation coefficient ranged from 0.25 to 0.65).These findings demonstrate that saliva phenytoin concentrations are increased by reductions in saliva flow rate. Caution is therefore required when saliva phenytoin concentrations are used for therapeutic monitoring in the presence of factors which may affect saliva flow rate.     

Effect of iron deficiency anaemia and its treatment on the absorption and elimination of phenformin

1. The extent of phenformin absorption and its rate of urinary excretion have been assessed in adult patients with iron deficiency anaemia, a condition which compromises gastrointestinal function. 2. Phenformin (100 mg) was administered orally to patients before treatment, three days after the start of a course of iron treatment (oral 300 mg b.d. or total intravenous iron) and at the end of 28 days, when haemoglobin was over 10 gm%. 3. No significant difference was found between mean total amounts of phenformin and 4-hydroxyphenformin excreted in urine, before treatment or after 3 or 28 days replacement therapy. It is concluded that phenformin absorption is not affected by iron deficiency. 4. In addition, iron deficiency had no significant effect on phenformin elimination half-life.     

舒林酸胶囊的人体相对生物利用度研究

目的：单剂量口服舒林酸胶囊（试验品）对普通片（对照品）的相对生物利用度研究。方法：按双周期交叉试验,８位健康男性受试者服药后,采用快速,准确ＨＰＬＣ法测定其血药浓度。以３ｐ９７药动学程序计算。结果：宁波昆厂生产的舒林酸胶囊对普通片的相对生物利用度为９７．６％;方差分析与双单侧检验示明,两制剂ＡＵＣ间无显著性差异（Ｐ〉０．０５）,试验品生物利用度参数ＡＵＣ平均值的９０％可信限（８９．７％－１０４．８     

Effect of iron deficiency anaemia and its treatment on the absorption and elimination of phenformin

1.The extent of phenformin absorption and its rate of urinary excretion have been assessed in adult patients with iron deficiency anaemia, a condition which compromises gastrointestinal function.

2.Phenformin (100 mg) was administered orally to patients before treatment, three days after the start of a course of iron treatment (oral 300 mg b.d. or total intravenous iron) and at the end of 28 days, when haemoglobin was over 10 gm%.

3.No significant difference was found between mean total amounts of phenformin and 4-hydroxyphenformin excreted in urine, before treatment or after 3 or 28 days replacement therapy. It is concluded that phenformin absorption is not affected by iron deficiency.

4.In addition, iron deficiency had no significant effect on phenformin elimination half-life.     

Comparative bioavailability of two capsule formulations of ofloxacin in healthy volunteers after a single dose administration

Abstract

The bioavailability of two ofloxacin (OFX) tablet formulations (OTT, test formulation from Laboratorio Atral SA - Portugal, and Tarivid, reference formulation from Hoechst AG - Germany) were compared in 24 (12M, 12F) healthy volunteers who received a single oral dose of 200 mg of each formulation in an open, randomized, two-period crossover fashion with a 14 day washout interval between doses. Plasma samples were obtained over a 24 h interval and OFX concentrations were determined by HPLC with UV detection. From the OFX plasma concentration vs time curves, the AUC_[0-24] (area under the concentration vs time curves from 0 to 24 h), AUC_[0-α] (area under the concentration vs time curves extrapolated to infinity), C_max (maximum concentration achieved), t_max (time to achieve C_max), t_1/2 (terminal first order elimination half-life), and elimination constant (K_e) were obtained. All these variables were analyzed using both parametric and non-parametric statistics. The two OFX tablet brands did not show statistically significant differences in bioavailability as assessed by the statistical analysis of AUC_[0-24] (14.8 and 14.7μg h ml^?1, respectively for OTT and Tarivid), AUC_[0-α] (16.0 and 15.6 μg h ml^?1), C_max (2.9 and 3.1 μg/ml), t_max (0.8 and 1.5 h), t_1/2 (5.9 and 5.6 h), and K_e (0.12 and 0.13 h^?1) values. Based on these results and on the United States Food and Drug Administration (FDA) requirements [1993], both formulations were considered to be bioequivalent.     

铁剂治疗小儿缺铁性贫血的药物经济学分析及用药选择

目的：为合理选用铁剂治疗小儿缺铁性贫血提供参考依据。方法：选择国内市场8种铁剂,以1岁小儿为例,计算出一个疗程所需每种铁剂总量的费用。并进行药物经济学最小成本分析。结果：费用从高到低依次为尼龙雪、速力菲、福乃得A、富马酸亚铁胶囊、益气维血颗粒、福乃得B、新血宝、硫酸亚铁片。结论：经济学分析,推荐选用益气维血颗粒、速力菲。     

Effect of dose on bioavailability of oral digoxin

Summary Nine healthy volunteers received single 0.25, 0.5, 1.0, 1.5, and 2.0 mg doses of oral digoxin tablets in random sequence on five occasions separated by at least 4 weeks. Urinary excretion of immunoassayable digoxin was determined from 8 consecutive 24 h urine samples collected after each dose. Mean values of cumulative urinary excretion of digoxin at the 5 doses were: 40.9, 35.6, 36.4, 34.1, and 33.5% of the dose (F=0.64; d. f.=4.32; N. S.). Mean values of urinary excretion half-life were: 2.48, 2.03, 2.20, 2.07, and 1.87 days (F=2.87; d. f.=4.32;p=0.05). Thus, the bioavailability of orally administered digoxin tablets in healthy volunteers is dose-independent over an 8-fold range of doses.Supported in part by the Deutsche Forschungsgemeinschaft, Bonn-Bad Godesberg, Federal Republic of Germany; by Sandoz Studienstiftung, Basel, Switzerland; and by Grant MH-12279 from the United States Public Health Service