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1.
Purpose. The sensitivity and effectiveness of indirect metrics proposedfor the assessment of comparative absorption rates in bioequivalencestudies [C max , T max , partial AUC(AUC p ), feathered slope (SL f ), interceptmetric (I)] were originally tested by assuming first-order absorption.The present study re-evaluates their sensitivity performances using themore realistic inverse Gaussian (IG) model characterizing the inputprocess for oral drug administration. Methods. Simulations were performed for both the first-order orexponential model (EX) which is determined by only one parameter, themean absorption time (MAT = 1/k a ), and the IG model, whichadditionally contains a shape parameter, the relative dispersion of absorptiontime distribution (CV 2 A ). Kinetic sensitivities (KS) of the indirectmetrics were evaluated from bioequivalence trials (error free data)generated with various ratios of the true parameters (MAT and CV 2 A ) of thetwo formulations. Results. The behavior of the metrics was similar with respect tochanges in MAT ratios with both models: KS was low with C max ,moderate with SL f and AUC p , and high with I and T max followingcorrection for apparent lag time (T lag ). Changes of the shape parameterCV 2 A , however, were not detectable by C max , T max , SL f , and AUC p .Changes in both MAT and CV 2 A were well reflected by I with CV 2 A - ratio> 1. I exhibited approximately full KS also with CV 2 A - ratio <1 when a correction was first applied for the apparent lag time. Conclusions. The time profile of absorption rates is insufficientlycharacterized by only one parameter (MAT). Indirect metrics which aresensitive enough to detect changes in the scale and shape of the inputprofile could be useful for bioequivalence testing. Among the testedmeasures, I is particularly promising when a correction is appliedfor T lag .  相似文献   

2.
《Pharmaceutical biology》2013,51(4):354-361
Context: Alocasia indica Schott (Araceae) is used in several regions of India, especially in rural communities, by traditional medicine practitioners to treat diarrhea. However, no scientific data are available to justify the traditional potentials of the plant species in gastrointestinal disorders.

Objective: To evaluate the antidiarrheal and in vitro antiprotozoal activities of extracts of leaves of Alocasia indica using various pharmacological models.

Materials and methods: In vitro antidiarrheal activity of aqueous and ethanol extracts of Alocasia indica was evaluated against Escherichia coli, Salmonella typhimurium, Shigella flexneri and Staphylococcus aureus by agar well diffusion method. In vivo antidiarrheal activity of the extracts was studied against recinolic acid-induced diarrhea and magnesium sulfate-induced diarrhea. The effect of the extracts on normal intestinal transit, recinolic acid-induced intestinal transit, recinolic acid-induced intestinal fluid accumulation (enteropooling) and gastric emptying was assessed. In vitro antiprotozoal activity of aqueous and ethanol extracts of Alocasia indica was studied against Entamoeba histolytica and Giardia intestinalis.

Results: The aqueous and ethanol extracts exhibited significant in vitro antidiarrheal activity compared to the standard drug ciprofloxacine (10 µg/mL). The plant extracts showed significant (P <0.05) and dose-dependent antidiarrheal activity comparable to that of the reference drug, loperamide (10?mg/kg). The plant extracts exhibited significant in vitro antiprotozoal activity against both protozoa compared to the standard amebicidal and giardicidal drugs, metronidazole and emetine.

Discussion and conclusion: The results showed that the extracts of Alocasia indica have significant antidiarrheal and in vitro antiprotozoal activities which support its use in traditional herbal medicine practice.  相似文献   

3.
Multicompartmental pharmacokinetics involves the four volumes: Vc = volume of the central compartment; Vss = volume of distribution steady-state; Vβ = volume of distribution beta; and Vext = the extrapolated volume of distribution. The ratio Vc/Vext is indicative of the degree of multicompartmental character of a set of data. The quantity (Vext/Vβ)?1 is the fractional error in the total clearance when one assumes a monoexponential rather than a polyexponential equation for disposition of a drug. The ratio Vss/Vβ indicates how well the one-compartment body model predicts average amounts of drug in the body when a multicompartmental model is actually operative. The quantity (Vss/Vc)? 1 is equal to either k12/k21 or k12/k21 + k13/k31 of the two- and three-compartmental mammillary models. Examples from the literature are reported and discussed.  相似文献   

4.
周莉  庞骁  陈勇  许莉  李素平 《安徽医药》2018,39(6):683-686
目的 探讨89SrCl2治疗恶性肿瘤骨转移的疗效影响因素。方法 选择南充市川北医学院附属医院2013年2月至2016年9月行89SrCl2治疗的恶性肿瘤骨转移患者99例,分析患者的年龄、性别、肿瘤病理类型、89SrCl2治疗次数、手术切除原发灶、放疗、化疗、肿瘤骨转移的病灶数量、联合止痛药状况以及碱性磷酸酶(ALP)是否会影响89SrCl2的治疗效果。结果 89SrCl2治疗的总有效率为63.6%。单因素分析结果显示不同肿瘤病理类型、不同治疗次数、是否联合放射治疗、是否手术切除原发灶、不同肿瘤骨转移病灶数量及是否联合止痛药患者的治疗效果进行比较,差异具有统计学意义(P<0.05)。logistics回归分析显示,患者的肿瘤病理类型、89SrCl2治疗次数、手术切除原发灶、肿瘤骨转移的病灶数量及联合止痛药是影响89SrCl2疗效的独立因素(P<0.05)。结论 肿瘤病理类型、89SrCl2治疗次数、手术切除原发灶、肿瘤骨转移病灶数量以及联合止痛药能影响89SrCl2治疗恶性肿瘤骨转移的疗效。  相似文献   

5.
Summary The effects of two doses of tolazoline have been compared in 2 groups of newborns suffering from the persistent fetal circulation syndrome. The effects on PaO2 and AaDO2 were similar in the 2 groups who received either a bolus of 1 or 0.5 mg·kg–1 tolazoline, followed by a continuous infusion of 1 or 0.5 mg·kg–1·h–1. The observed changes did not differ significantly from those previously observed in babies treated with 2 mg·kg–1. A rise in PaO2 and a reduction in AaDO2 were usually observed shortly after the bolus injection and at plasma levels between 1.5 and 4 µg·ml·–1. A progressive rise in plasma level over time occurred after 1 mg·kg–1 (and in the previous study of 2 mg) but not with 0.5g/kg tolazoline. The elimination half-life of tolazoline in 6 patients was 5 to 13 h. The data suggest that continuous infusion of tolazoline is not necessarily required and that the dose of 0.5 mg/kg is more appropriate and safer than the higher doses usually proposed.  相似文献   

6.
Purpose. The relationship between the pH, solubility, and partition coefficient was investigated to show that the product of intrinsic values of solubility and partition coefficient is equal to the product of total values of solubility and distribution coefficient at different pH. Methods. The pH distribution profiles were obtained from the literature and the pH solubility profiles were obtained from the literature or calculated from their intrinsic solubility and pK a. Results. The pH solubility and pH distribution coefficient profiles of 25 compounds were investigated to show that the product of intrinsic solubility (S w) and intrinsic octanol-water partition coefficient (K ow) is equal to the product of total solubility of a partially ionized solute (S T) and its octanol-buffer distribution coefficient (K D) at any pH where ion pair formation and salt precipitation are not present. Conclusions. The fact that S w K ow can be used instead of S T K D to model the absorption of partially ionized drugs in the gastrointestinal tract has important biopharmaceutical implications.  相似文献   

7.
Summary The present investigation was undertaken to test the hypothesis that the experimentally determined degree of supersensitivity to an agonist caused by inhibition of a site of loss depends on the ratio K m of the site of loss/ED50 of the agonist.The influence of inhibition of neuronal uptake by cocaine on the -adrenoceptor-mediated effect of noradrenaline was studied on the dog saphenous vein; the influence of inhibition of COMT by U-0521 on the -adrenoceptor-mediated effect of isoprenaline was studied on the dog saphenous vein and on the guinea-pig trachea; the influence of inhibition of acetylcholinesterase by physostigmine on the effect of acetylcholine was studied on the guinea-pig ileum. To further extend the range of values of the ratio K m/ED50, several concentrations of phentolamine, propranolol or atropine were used to increase the ED50 of the respective agonist. It was thus possible to determine the degree of supersensitivity caused by inhibition of a site of loss over a range of K m/ED50 values of 0.02 to 2,307.In seven situations the ratio K m/ED50 was higher than 10. In all of these cases the supersensitivity caused by inhibition of the site of loss was maximal. In eleven situations the ratio K m/ED50 was less than 10 and higher than 0.1 and the supersensitivity obtained was sub-maximal but was closer to the maximum, the closer the ratio was to 10. In two situations the ratio was less than 0.1 and no supersensitivity was obtained.The results confirm the hypothesis.  相似文献   

8.
Context The underground edible tuber of Dioscorea alata L. (Dioscoreaceae) is a functional food with high nutritive value and therapeutic potential. The tuber is known to possess anti-inflammatory properties in traditional medicine.

Objective The present study explores the anti-inflammatory activity and standardisation of D. alata tuber hydromethanol extract.

Materials and methods Hydromethanol extract (70%) of D. alata tuber was chemically characterised using HPLC and GC-MS techniques. Murine lymphocytes were cultured for 48?h with six different concentrations (0–80?μg/mL) of the extract. The expression of nitric oxide (NO), TNF-α, COX-1, COX-2, and PGE2 were evaluated using colorimetric and ELISA methods.

Results Dioscorea alata extract inhibited the expression of NO and TNF-α with an IC50 value of 134.51?±?6.75 and 113.30?±?7.44?μg/mL, respectively. The IC50 values for inhibition of total COX, COX-1, COX-2 activities and PGE2 level were 41.96?±?3.07, 141.41?±?8.99, 32.50?±?1.69, and 186.34?±?15.36?μg/mL, respectively. Inhibition of PGE2 level and COX-2 activity was positively correlated (R2?=?0.9393). Gallic acid (GA), 4-hydroxy benzoic acid (4HBA), syringic acid (SYA), p-coumaric acid (PCA), and myricetin (MY) were identified and quantified using HPLC. GC-MS analysis revealed the presence of 13 different phytocompounds such as hexadecanoic acid, methyl stearate, cinnamyl cinnamate, and squalene.

Conclusion The D. alata extract significantly down-regulated the pro-inflammatory signals in a gradual manner compared with control (0?μg/mL). Different bioactive phytocompounds individually possessing anti-inflammatory activities contributed to the overall bioactivity of the D. alata tuber extract.  相似文献   

9.
  1. Prostanoids induce a wide range of biological actions which are mediated by specific membrane-bound receptors. We have recently shown that the E-type prostaglandins, PGE1 and PGE2, effectively inhibit eosinophil aggregation induced by platelet-activating factor (PAF). In an attempt to determine which prostanoid receptor(s) were involved, we investigated the effects of a range of selective prostanoid agonists and antagonists on eosinophil homotypic aggregation induced by PAF.
  2. Both PGE1 and PGE2 (10−10 to 10−6M) induced a concentration-related inhibition of the aggregation response induced by PAF. PGE1 was more effective than PGE2 but PGE2 was slightly more potent than PGE1 (approximate IC50 values for PGE1 and PGE2 of 1.5×10−8M and 5×10−9M, respectively).
  3. The EP2-selective agonists, 11-deoxy-PGE1, butaprost and AH13205, and the EP2/EP3-selective agonist, misoprostol, also inhibited PAF-induced aggregation. The rank order of potency for EP2-selective agonists was 11-deoxy-PGE1 > misoprostol > butaprost = AH13205. The protein kinase A inhibitor, KT5720 (10−6M), reversed the inhibitory effects of 11-deoxy-PGE1 (10−6M) and AH13205 (10−5M).
  4. The EP1/EP3-selective agonist, sulprostone, and the EP1-selective agonist, 17-phenyl-ω-trinor PGE2, had no significant inhibitory activity when tested at concentrations up to 10−6M. The EP4-receptor antagonist, AH23848B, had no effect on PAF-induced aggregation and did affect the inhibitory activity of PGE1.
  5. The IP-selective agonist, cicaprost (up to 10−6M), and the IP/EP1-receptor agonist, iloprost (up to 10−5M), had no significant effect on PAF-induced eosinophil aggregation. However, iloprost significantly augmented the inhibitory effects of a maximally inhibitory concentration of PGE2.
  6. PGD2 (10−5M) had no effect on eosinophil aggregation and the inhibitory activity of PGE1 on PAF-induced eosinophil aggregation was not altered by the DP-selective receptor antagonist, BWA868C.
  7. The results presented here suggest that the inhibition of PAF-induced eosinophil aggregation by prostanoids is mediated by the occupation of EP2-receptors. It is important to note that the effects of naturally occuring prostanoids, such as PGE2, on eosinophil aggregation occur at low concentrations highlighting a potential role for EP2 receptors in regulating eosinophil function in vivo.
  相似文献   

10.
Summary The pharmacokinetics of alinidine was investigated in two groups of volunteers: Group I (N=5) received on two different occasions single doses of14C-labelled drug given orally (40 mg) or intravenously (10 mg); Group II (N=6) received single oral doses 10, 30 or 90 mg dissolved in 20 ml water. The samples from Group I were analysed by two different and independent methods (RIA and counting total radioactivity). The results obtained by the two methods were identical, since the compound was not metabolized. The plasma concentrations and renal excretion data obtained from both groups were individually fitted to an open three compartment model. Independent of the route of administration and of the doses given, similar pharmacokinetic parameters were calculated for each group and each trial. The half lives of the distribution and elimination phases were t1/2: 36–41 s, t1/2 : 9.9–11.1 min and t1/2: 2.7–3.8 h. There was a linear relationship between the dose administered and the resulting areas under the plasma concentration curves (AUC). Following a lag period (=0.19–0.22 h), the peak plasma concentration was reached 0.6–1.2 h after oral administration. Oral alinidine was 100% bioavailable.  相似文献   

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