252例儿童哮喘的门诊治疗和管理

目的为探讨儿童哮喘得到长期缓解有效方法。方法我们开展前瞻性的对２５２例哮喘儿童进行了门诊治疗与管理和家庭治疗与自我管理相结合地研究,强调长期规范治疗,并对部分患儿进行了缓解期肺功能的测定,以此评价疗效。结果经半年～１年随访,系统管理治疗规范组哮喘缓解率明显高于间歇规范组及不规范组（Ｐ＜０００１）。缓解期肺功能测定也表明规范组肺功能基本正常率明显高于其他两组（Ｐ＜００５）。结论儿童哮喘要得到长期缓解及根本控制,必须要有系统的门诊治疗管理和家庭治疗与自我管理相结合。     

Pharmacokinetic aspects of rectal formulations of Temazepam

An in vitro/in vivo study was carried out with different rectal formulations of temazepam. Pharmacokinetic data were determined in a cross-over study in 10 volunteers after rectal administration of 10 mg temazepam as a polyethylene glycol based suppository (selected from in vitro data), a liquid-filled capsule and a micro-enema respectively, using oral administration of a liquid-filled capsule as a reference. Serum levels of temazepam indicate an instantaneous and complete release from the micro-enema (F_rel=0.94±0.21, C_max 205±36.9 g/l, t_max 0.49±0.31 hour) and a slower but complete release of temazepam from the suppository (F_rel=1.01±0.25, C_max 202±41.3 g/l, t_max 1.48±0.41 hour). A high interindividual variation in absorption profiles was observed after rectal administration of the liquid-filled capsule (F_rel 0.72±0.36, C_max 182±122 g/l, t_max 4.08±4.28 hour), which makes it less suitable for rectal use. The micro-enema and suppository appear to be useful as rectal formulations for temazepam.     

Absorption Enhancing Effect of Cyclodextrins on Intranasally Administered Insulin in Rats

The absorption enhancing effect of -, -, and -cyclodextrin (CD), dimethyl--cyclodextrin (DMCD), and hydroxypropyl--cyclodextrin (HPCD) on intranasally administered insulin was investigated in rats. Coadministration of 5% (w/v) DMCD to the insulin solution resulted in a high bioavailability, 108.9 ± 36.4% (mean ± SD, n = 6), compared to i.v. administration, and a strong decrease in blood glucose levels, to 25% of their initial values. Coadministration of 5% -CD gave rise to an insulin bioavailability of 27.7 ± 11.5% (mean ± SD, n = 6) and a decrease in blood glucose to 50% of its initial value. The rate of insulin absorption and the concomitant hypoglycemic response were delayed for the -CD-containing solution as compared to the DMCD preparation. The other CDs, HPCD (5%), -CD (1.8%), and -CD (5%), did not have significant effects on nasal insulin absorption. DMCD at a concentration of 5% (w/v) induces ciliostasis as measured on chicken embryo tracheal tissue in vitro, but this effect is reversible. In conclusion, DMCD is a potent enhancer of nasal insulin absorption in rats.     

Salbutamol disposition and dynamics in conscious rabbits: Influence of the route of administration and of the dose

This study assessed the influence of dose and route of administration on salbutamol kinetics and hypokaliemic effect. Salbutamol plasma kinetics were studied in a first group of 6 rabbits who received 60, 800, and 60 g/kg by the intravenous (iv), oral (po), and intratracheal (it) routes, respectively, at 1-week intervals. A second group of 6 rabbits received 120, 2400, and 120 g/kg of salbutamol by the same three routes. Multiple blood samples were withdrawn to assay salbutamol and potassium. Following iv salbutamol (60 g/kg), total plasma clearance was 82±5 ml/min per kg, apparent volume of distribution was 5.0±0.5 l/kg, and terminal half- life was 41±2 min. Similar values were estimated when 120 g/kg of salbutamol was administered iv or was given po or it. The bioavailability of po and it salbutamol was approximately 1 and 20%, respectively. For the first group, the maximal decrease in plasma potassium elicited by salbutamol was 0.80±0.19, 0.48±0.22, and 0.78±0.46 mmol/l, and for the second group, maximal decrement was 1.31±0.37, 0.70±0.24, and 0.84±0.17 mmol/l for the iv, po, and it routes, respectively. Compared to salbutamol peak plasma concentrations, maximal decrease in plasma potassium appeared between 60 and 108 min later for the iv route, 90 and 25 min later for po and it routes, and for this reason, the hypokaliemic effect was not associated to salbutamol plasma concentrations. The hypokaliemic effect was dependent upon the route, e.g., po>it>iv. It is concluded that (i) salbutamol plasma kinetics are first-order independently of the route of administration, and (ii) salbutamol hypokaliemic effect is modulated by the dose and the route of administration.List of abbreviations AUC Area under salbutamol plasma concentration-time curve - cl_INT Salbutamol intrinsic clearance - cl_T Salbutamol total plasma clearance - c_MAX Salbutamol maximal plasma concentration - F Fraction of the dose of salbutamol reaching the systemic circulation - iv Intravenous route of administration - it Intratracheal route of administration - po Oral route of administration - V_area Salbutamol apparent volume of distribution - T ₂ ¹ Salbutamol half-life of the terminal phase - t_MAX Time to observe the maximal decrease in plasma potassium - e_MAX Predicted maximal effect of salbutamol - EC₅₀ Concentration of salbutamol eliciting 50% of e_MAX Supported by the Medical Research Council of Canada (MT-10874). Sylvie Perreault is recipient of a Bourse Formation de troisième cycle des Fonds de la Recherche en Santé du Québec.     

Behaviour of glibenclamide on repeated administration to diabetic patients

Summary Six maturity onset diabetic patients took glibenclamide 5 mg by mouth, every morning 10 min before a standard breakfast. Serum levels of immunoreactive glibenclamide, glucose and immunoreactive insulin were measured repeatedly on the first and 15th days of treatment. Measured glibenclamide blood levels were in close agreement with an analogue computer simulation of data obtained from healthy volunteers: there was no accumulation of drug in the blood, but there was strong evidence for the existence of a slowly equilibrating deep compartment. Considerable insulin release and correction of the breakfast-induced hyperglycaemia were observed immediately after administration of the drug, as well as 5 h later, at lunch time. The clinical significance of blood levels of glibenclamide, as well as the correlation of pharmacokinetics with pharmacodynamics, are discussed in the light of these results.Glossary of symbols IR- immuno-reactive - GLI glibenclamide - IRI immuno-reactive insulin - GLU glucose - AK 1 values obtained with patient AK on the first day of treatment - AK 15 values obtained with patient AK on the 15th day of treatment - b serum level - b_max maximal serum level - t time after dose - t_max time of maximal serum level - G gastro-intestinal system - B central compartment (blood) - T peripheral compartment (tissue) - E excreta - M,N coefficients of the equation of a bi-exponential decay curve - µ, v exponents of the equation of a bi-exponential decay curve - e base of natural logarithms - K_BG K_EB K_TB K_BT first order rate constants (e. g. K_BG means: into B, from G) - K_BG first order rate constants - etc. not corrected for the volume of distribution     

Pharmacokinetics of methyldopa in healthy man

Summary The pharmacokinetics of 2-¹⁴C-L--methyldopa have been investigated in five healthy volunteers following intravenous and oral administration. In the intravenous study a bi-phasic plasma concentration curve was found both for chemically determined -methyldopa and for radioactivity. The plasma level of radioactivity differed significantly from chemically determined drug, a pattern which was also found in urine. This suggests the presence of unidentified metabolite(s). The difference between plasma disappearance and urine recovery of -methyldopa and radioactivity during the first 4 h after injection suggests distribution to an extravascular compartment. Plasma half-lives of total radioactivity and of unchanged drug were calculated. In three subjects, pharmacokinetic parameters for a two-compartment open body model were calculated from urine and plasma data. Urinary recovery of radioactivity was almost complete within 48 h after intravenous administration. After oral administration, however, only about 40 per cent of the radioactive dose was recovered in the urine, and it contained approximately equal amounts of unconjugated methyldopa, acid-labile conjugated methyldopa and unidentified metabolite(s). The acid-labile conjugate was found only after oral administration, which supports the theory of a mucosal conjugation process. The lack of acid-labile conjugated drug either in the plasma or urine after intravenous injection indicates that there is no enterohepatic circulation of this drug.     

药事管理学科科研问题及对策浅析

分析当前我国药事管理学科科研中存在的问题和原因。提出发展科研的思路与方法。     

对现代病证结合论治方法的整理与研究

半目前病证结合论治方法整理归纳为：西医诊病，中医治证；中医疾病的病证结合论治；用中医理论辨西医疾病之基本病机论治；西医疾病分期论治；专病专方治疗；专病专药治疗；中西医药联合治疗。并对每种形式的特点进行了分析研究。     

436例小儿肺炎的中西医结合治疗

对436例肺炎患儿在抗生素治疗的同时，给予清热宣肺，化痰平喘，健脾益气，养阴清肺中药口服，结果总有效率达97．25％。中西医结合治疗小儿肺炎可以缩短病程，减少抗生素的使用。