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71.
Sylvie Perreault Huy Ong Patrick du Souich 《Journal of pharmacokinetics and pharmacodynamics》1992,20(5):461-476
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 Multiple blood samples were withdrawn to assay salbutamol and potassium.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
- clINT
Salbutamol intrinsic clearance
- clT
Salbutamol total plasma clearance
- cMAX
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
- Varea
Salbutamol apparent volume of distribution
- T
2
1
Salbutamol half-life of the terminal phase
- tMAX
Time to observe the maximal decrease in plasma potassium
- eMAX
Predicted maximal effect of salbutamol
- EC50
Concentration of salbutamol eliciting 50% of eMAX
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. 相似文献
72.
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
- bmax
maximal serum level
- t
time after dose
- tmax
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
- KBG KEB KTB KBT
first order rate constants (e. g. KBG means: into B, from G)
- KBG
first order rate constants
- etc.
not corrected for the volume of distribution 相似文献
73.
Ø. Stenbæk E. Myhre H. Erik Rugstad Elisabeth Arnold T. Hansen 《European journal of clinical pharmacology》1977,12(2):117-123
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. 相似文献
74.
75.
76.
436例小儿肺炎的中西医结合治疗 总被引:1,自引:0,他引:1
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。 相似文献
77.
胰岛素鼻腔给药微球剂的制备及药效学研究 总被引:6,自引:1,他引:6
目的 :制备胰岛素鼻腔给药微球剂并进行药效学研究。方法 :以可溶性淀粉为原料 ,利用聚乙二醇法制备淀粉微球 ,吸附胰岛素 ,制得含胰岛素的淀粉微球。根据Baldwin法进行药效学研究。结果 :制得的胰岛素微球鼻腔给药后可使血液中血糖浓度下降35 2%。结论 :胰岛素微球经鼻腔给药可明显降低血糖水平 ,药物作用呈现缓释特征。 相似文献
78.
口服或阴道用米索前列醇用于人工流产术前宫口扩张的比较 总被引:2,自引:0,他引:2
目的 :比较在人工流产术前阴道或口服用米索前列醇后宫口扩张的临床效果。方法 :将 16 1例行人工流产术的早孕妇女分成 3组。第 1组 5 3例和第 2组 5 7例于术前 1h分别经阴道用米索前列醇和口服米索前列醇各 4 0 0 μg ,第 3组为对照组5 1例 ,术前不用任何药物。结果 :第 1组和第 2组宫口扩张有效率分别是 92 % (49/ 5 3)和 89% (5 1/5 7) ,明显高于对照组 0 (0 / 5 1,P <0 .0 1) ;前 2组术中无需使用局部麻醉 (0 / 5 3和 0 / 5 7) ,而对照组则有 74 % (38/ 5 1)的病人需加用局部麻醉 (P <0 .0 1) ;前 2组术中出血量为 (7±s 4 )mL和 (7± 3)mL ,也少于对照组 (12± 4 )mL ,差异有非常显著意义 (P <0 .0 1)。阴道用米索前列醇组与口服米索前列醇组相比 ,术中扩宫口作用差异无显著意义 (P >0 .0 5 ) ,但口服用药组不良反应多于阴道用药组。结论 :阴道用米索前列醇组、口服米索前列醇组术中扩宫口作用肯定 ,出血量小、不良反应轻 ,两者疗效相似 相似文献
79.
Yoshinori Ebato Yoshinori Kato Hiraku Onishi Tsuneji Nagai Yoshiharu Machida 《Drug development research》2003,58(3):253-257
A simple method for the preparation of the inner liposomes for double liposomes (DL) was developed. The encapsulation efficiency of erythrosine in liposomes prepared by this new method is superior to that of the previous method because of the concentration of the drug in the lipid membrane. To evaluate the usefulness of DL prepared by the glass‐filter method modified in this study as an oral dosage form of salmon calcitonin (SCT), a suspension of liposomes containing SCT was administered to rats at a dose of 10 μg SCT/kg. Each type of DL showed better efficacy than its inner liposomes alone. The decrease in plasma calcium level was dependent on the electrical charge and particle size of the inner liposomes. The hypocalcemic efficacy of DL encapsulating SCT‐loading cationic liposomes relative to that after subcutaneous administration of SCT at a dose of 1 μg/kg was 6.47%, which was the largest value obtained. These results indicated that not only the particle size but also the electrical charge of inner liposomes affect intestinal absorption. This study verified that the efficacy was increased because of the decrease in diameter of the inner liposomes and the use of lipid with a positive charge. These findings concluded that DL might be useful as an oral dosage form of SCT. Drug Dev. Res. 58:253–257, 2003. © 2003 Wiley‐Liss, Inc. 相似文献
80.
探讨 5 FU超声雾化吸入联合放疗及全身化疗治疗非小细胞肺癌 (NSCLC)的疗效 ,探讨一种新的非手术综合治疗方案。60例非小细胞肺癌患者随机分为两个组。研究组采用 5 FU超声雾化吸入联合常规放疗及以顺铂为主的全身化疗 2个周期 ,对照组采用常规放疗及全身化疗。结果示研究组和对照组的总有效率分别为 86 67%(2 6/3 0 )和 63 3 3 % (19/3 0 ) ,χ2 =4 3 5 6,P <0 0 5。 1、2、3年生存率研究组为 79 89%、5 6 2 6%和 3 0 3 9% ;对照组分别为 5 1 5 7%、3 4 81%和 11 60 % ,χ2 =4 42 1,P <0 0 5。两组的毒副反应差别无统计学意义 ,P >0 0 5。 5 FU超声雾化吸入联合放疗和以顺铂为主的全身化疗提高了NSCLC的 1、2、3年生存率 ,毒副反应可耐受 ,是一种有效的非手术综合治疗方案。 相似文献