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排序方式: 共有353条查询结果,搜索用时 15 毫秒
1.
The pharmacokinetics of artemisinin after oral, intramuscular and rectal administration to volunteers 总被引:4,自引:0,他引:4
H A Titulaer J Zuidema P A Kager J C Wetsteyn C B Lugt F W Merkus 《The Journal of pharmacy and pharmacology》1990,42(11):810-813
The pharmacokinetics after oral, intramuscular and rectal administration of artemisinin, a new potent antimalarial drug, to healthy volunteers has been examined. The study was set-up as a four-way cross-over design with a wash-out period of one week between the test days. In ten volunteers artemisinin concentrations in serum were monitored using a reversed phase HPLC assay with UV detection after derivatization. After oral administration, artemisinin was rapidly but incompletely absorbed, the mean absorption time was 0.78 h and the bioavailability relative to the intramuscularly injected suspension in oil 32%. The mean residence time of the latter (10.6 h) was 3 times that of the oral formulation (3.4 h). This seems to enable a twice daily dosage regimen for the intramuscular oil injection, while the oral formulation necessitates a more frequent dosing interval. After intramuscular injection and rectal administration of an aqueous suspension, very low and variable artemisinin concentrations in serum were observed, probably indicating a poor and erratic absorption. 相似文献
2.
Adverse health effects of prenatal and postnatal tobacco smoke exposure on children. 总被引:6,自引:0,他引:6
Parents who choose to smoke are possibly not aware of, or deny, the negative effects of passive smoking on their offspring. This review summarises a wide range of effects of passive smoking on mortality and morbidity in children. It offers paediatricians, obstetricians, specialists in preventive child health care, general practitioners, and midwives an approach to promote smoking cessation in smoking parents before, during, and after pregnancy. 相似文献
3.
Drugs in nasal preparations, for local use as well as for systemic use, should not interfere with the self-cleaning capacity of the nose, effectuated by the ciliary epithelium. Many drugs and additives, however, have a negative effect on nasal ciliary function. Examples of ciliotoxic agents are lipophilic and mercuric preservatives, local anesthetics, antihistamines, propranolol, and absorption enhancers such as the bile salts. Cholinergic drugs and -adrenergic drugs exert a ciliostimulatory effect. It is the purpose of this review to summarize the present knowledge of ciliotoxicity of drugs and additives and to give recommendations for the use of ciliofriendly drugs in nasal preparations. 相似文献
4.
Marttin Emmeline Verhoef J. Coos Cullander Christopher Romeijn Stefan G. Nagelkerke J. Fred Merkus Frans W. H. M. 《Pharmaceutical research》1997,14(5):631-637
Purpose. To visualize the transport pathway(s) of high molecular weight model compounds across rat nasal epithelium in vivousing confocal laser scanning microscopy. Furthermore, the influence of nasal absorption enhancers (randomly methylated -cyclodextrin and sodium taurodihydrofusidate) on this transport was studied.
Methods. Fluorescein isothiocyanate (FITC)-labelled dextrans with a molecular weight of 3,000 or 10,000 Da were administered intranasally to rats. Fifteen minutes after administration the tissue was fixed with Bouin. The nasal septum was surgically removed and stained with Evans Blue protein stain or DiIC18(5) lipid stain prior to visualization with the confocal laser scanning microscope.
Results. Transport of FITC-dextran 3,000 across nasal epithelium occurred via the paracellular pathway. Endocytosis of FITC-dextran 3,000 was also shown. In the presence of randomly methylated -cyclodextrin 2% (w/v) similar transport pathways for FITC-dextran 3,000 were observed. With sodium taurodihydrofusidate 1% (w/v) the transport route was also paracellular with endocytosis, but cells were swollen and mucus was extruded into the nasal cavity. For FITC-dextran 10,000 hardly any transport was observed without enhancer, or after co-administration with randomly methylated -cyclodextrin 2% (w/v). Co-administration with sodium taurodihydrofusidate 1% (w/v) resulted in paracellular transport of FITC-dextran 10,000, but morphological changes, i.e. swelling of cells and mucus extrusion, were observed.
Conclusions. Confocal laser scanning microscopy is a suitable approach to visualize the transport pathways of high molecular weight hydrophilic compounds across nasal epithelium, and to study the effects of absorption enhancers on drug transport and cell morphology. 相似文献
5.
Bioavailability of intranasal formulations of dihydroergotamine 总被引:1,自引:0,他引:1
van der Kuy PH Lohman JJ Hooymans PM Ter Berg JW Merkus FW 《European journal of clinical pharmacology》1999,55(9):677-680
Objective: A comparison of the pharmacokinetic properties of two novel intranasal preparations of dihydroergotamine mesilate (DHEM)
with a commercially available intranasal preparation.
Methods: Two intranasal formulations of DHEM in combination with randomly methylated β-cyclodextrin (RAMEB) were prepared. Subsequently,
in an open, randomised, crossover study in nine healthy volunteers, the following medication was administered: 2 mg DHEM/2%
RAMEB nasal spray ( =two puffs of 100 μl); 2 mg DHEM/4 mg RAMEB nasal powder; 2 mg Diergo nasal spray ( =four puffs of 125 μl);
0.5 mg DHEM i.m., and 2 mg DHEM solution p.o.
Results: No statistically significant differences were found in maximum plasma concentration (Cmax), time to reach Cmax (tmax), area under plasma concentration–time curve (AUC0–8 h), Frel(t=8 h) and Cmax/ AUC(t=8 h) for the three intranasal preparations. The relative bioavailabilities of the DHEM/RAMEB nasal spray, the DHEM/RAMEB nasal
powder and the commercially available DHEM nasal spray were 25%, 19% and 21%, respectively, in comparison with i.m. administration.
The relative bioavailability after oral administration was 8%.
Conclusion: The pharmacokinetic properties of the novel intranasal preparations are not significantly different from the commercially
available nasal spray. Advantages of the DHEM/RAMEB nasal spray are (1) less complicated handling, (2) reduction of the number
of puffs and (3) a preference by the volunteers.
Received: 12 February 1999 / Accepted in revised form: 23 August 1999 相似文献
6.
Absorption Enhancing Effect of Cyclodextrins on Intranasally Administered Insulin in Rats 总被引:4,自引:0,他引:4
Merkus Frans W. H. M. Verhoef J. Coos Romeijn Stefan G. Schipper Nicolaas G. M. 《Pharmaceutical research》1991,8(5):588-592
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. 相似文献
7.
Bronchodilation in infants with malacia or recurrent wheeze. 总被引:3,自引:0,他引:3
W Hofhuis E C van der Wiel H A W M Tiddens G Brinkhorst W P J Holland J C de Jongste P J F M Merkus 《Archives of disease in childhood》2003,88(3):246-249
BACKGROUND: Controversy remains regarding the effectiveness of bronchodilators in wheezy infants. AIMS: To assess the effect of inhaled beta(2) agonists on lung function in infants with malacia or recurrent wheeze, and to determine whether a negative effect of beta(2) agonists on forced expiratory flow (V'(maxFRC)) is more pronounced in infants with airway malacia, compared to infants with wheeze. METHODS: We retrospectively analysed lung function data of 27 infants: eight with malacia, 19 with recurrent wheeze. Mean (SD) age was 51 (18) weeks. Mean V'(maxFRC) (in Z score) was assessed before and after inhalation of beta(2) agonists. RESULTS: Baseline V'(maxFRC) was below reference values for both groups. Following inhalation of beta(2) agonists the mean (95% CI) change in mean V'(maxFRC) in Z scores was -0.10 (-0.26 to 0.05) and -0.33 (-0.55 to -0.11) for the malacia and wheeze group, respectively. CONCLUSIONS: In infants with wheeze, inhaled beta(2) agonists caused a significant reduction in mean V'(maxFRC). Infants with malacia were not more likely to worsen after beta(2) agonists than were infants with recurrent wheeze. 相似文献
8.
Mascha P van den Berg J Coos Verhoef Stefan G Romeijn Frans W H M Merkus 《European journal of pharmaceutics and biopharmaceutics》2004,58(1):131-135
The uptake of estradiol and progesterone into the cerebrospinal fluid (CSF) after intranasal and intravenous administration in rats was investigated. Each animal received estradiol intranasally (40 microg/rat) and by intravenous infusion (10 microg/rat) into the jugular vein using a vascular access port. Hereafter, the same set of rats was treated with progesterone intranasally (200 microg/rat) and by intravenous infusion (104 microg/rat). Following nasal delivery, both steroid hormones reach Cmax values in plasma and CSF at 15 min after administration. Intravenous infusion of estradiol and progesterone shows comparable plasma and CSF concentration-time profiles compared to the nasal route. For both hormones the AUCCSF/AUCplasma ratios (mean +/- SD) after intranasal delivery (estradiol 2.3 +/- 1.1%; progesterone 1.9 +/- 0.7%) do not differ significantly from the ratios shown after intravenous infusion (estradiol 2.0 +/- 0.6%; progesterone 2.2 +/- 0.8%). These results indicate that after nasal delivery estradiol and progesterone are rapidly absorbed into the systemic circulation, from where the non-protein bound hormones probably enter the CSF by crossing the blood-brain barrier. No extra direct nose-CSF transport could be demonstrated. 相似文献
9.
10.
Mark M. P. van den Dorpel Ilkka Heinonen Sanne M. Snelder Hendrik J. Vos Oana Sorop Ron T. van Domburg Daphne Merkus Dirk J. Duncker Bas M. van Dalen 《The international journal of cardiovascular imaging》2018,34(5):743-749
Left ventricular (LV) diastolic dysfunction is one of the important mechanisms responsible for symptoms in patients with heart failure. The aim of the current study was to identify parameters that may be used to detect early signs of LV diastolic dysfunction in diabetic pigs on a high fat diet, using conventional and speckle tracking echocardiography. The study population consisted of 16 healthy Göttingen minipigs and 18 minipigs with experimentally induced metabolic dysfunction. Echocardiography measurements were performed at baseline and 3-month follow-up. The ratio of peak early (E) and late filling velocity (E/A ratio) and the ratio of E and the velocity of the mitral annulus early diastolic wave (E/Em ratio) did not change significantly in both groups. Peak untwisting velocity decreased in the metabolic dysfunction group (? 30.1?±?18.5 vs. ? 23.4?±?15.5 °/ms) but not in controls (? 38.1?±?23.6 vs. ? 42.2?±?23.0 °/ms), being significantly different between the groups at the 3-month time point (p?<?0.05). In conclusion, whereas E/A ratio and E/Em ratio did not change significantly after 3 months of metabolic dysfunction, peak untwisting velocity was significantly decreased. Hence, peak untwisting velocity may serve as an important marker to detect early changes of LV diastolic dysfunction. 相似文献