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Pharmacodynamic Profiles (pharmacodynamic + profile)
Selected AbstractsPharmacodynamics of S-2150, a Simultaneous Calcium-blocking and ,1 -Inhibiting Antihypertensive Drug, in RatsJOURNAL OF PHARMACY AND PHARMACOLOGY: AN INTERNATI ONAL JOURNAL OF PHARMACEUTICAL SCIENCE, Issue 3 2000TORU ISHIBASHI The in-vivo pharmacodynamics of S-2150, a newly developed dual-blocking type antihypertensive drug, was evaluated following intravenous infusion to rats. Previous in-vitro studies showed that the drug has two distinct mechanisms of antihypertensive effect,calcium-channel blocking activity and ,1 -adrenoceptor antagonism,which could be explained by a combination of two different pharmacodynamic models. The present in-vivo study showed that S-2150 also displays a complex pharmacodynamic profile (as measured by the decrease in mean blood pressure), which could be described by a combination of two sigmoid Emax models independently connected with the central compartment and the effect compartment. These results suggested that the dual-blocking mechanism of S-2150, which has been observed in in-vitro experiments, was also evaluated by the pharmacodynamic analysis of in-vivo experimental data. [source] Treatment of choroidal neovascularization using intravitreal bevacizumabACTA OPHTHALMOLOGICA, Issue 5 2007Robert Pedersen Abstract. Purpose:, This study aimed to assess the pharmacodynamic profile of intravitreal bevacizumab in relation to best corrected visual acuity (BCVA), foveal thickness, and other aspects of macular morphology after intravitreal injection of bevacizumab in eyes with subretinal choroidal neovascularization (CNV). Methods:, A retrospective observational, uncontrolled case series including 26 eyes in 25 patients followed for up to 6 months after intravitreal injection of bevacizumab 1 mg repeated as deemed necessary after monthly assessments by biomicroscopy, optical coherence tomography, colour fundus photography, fluorescein angiography and BCVA determination. At follow-up, cases were classified by morphological treatment response (reduction or elimination of pathological neovascular leakage, retinal thickening or serous retinal detachment) or absence of response (deterioration or lack of improvement). Primary disease entities included age-related macular degeneration (22 eyes, four of which had evidence of retinal angiomatous proliferation), idiopathic peripapillary neovascularization (one eye), and angioid streaks (three eyes in two patients). Results:, One month after the first injection, apparent morphological improvement was observed in 24/26 eyes and mean BCVA had improved by 3.1 ± 7.8 letters (p = 0.05). Of these 24 responders, which included all primary diagnoses, 11 (46%) demonstrated BCVA improvement of ,,5 letters. The two non-responders (7.7%) had lost >,3 lines of vision at 2 months follow-up. Overall, 18 eyes completed 6 months follow-up, with a mean BCVA improvement of 0.5 ± 12.7 letters, and 22 eyes completed 3 months follow-up, with a mean BCVA improvement of 2.0 ± 11.0 letters. Two months after the first injection, 11 (46%) of the 24 responders demonstrated signs of recurrent CNV activity, defined as decreased BCVA and/or increased retinal thickness and/or fluorescein angiographic CNV leakage. No serious drug-related adverse events were observed during the course of the study. Conclusions:, Overall mean BCVA remained stable throughout the study. Morphological signs of reduced CNV activity were seen in the majority of eyes at 2,4 weeks after intravitreal bevacizumab injection. Half the responders showed signs of renewed CNV activity at 2 months after their first injection. All first-injection responders were also second-injection responders. [source] Insulin analogues: an example of applied medical scienceDIABETES OBESITY & METABOLISM, Issue 1 2009B. Sheldon Insulin analogues were developed to try and achieve more physiological insulin replacement from injection in the subcutaneous site. Their pharmacokinetics and pharmacodynamics differ from human insulin when injected subcutaneously because of alterations in the amino acid sequence of the insulin molecule. The rapid-acting insulin analogues, lispro, aspart and glulisine, have a rapid onset of action and shorter duration of action because of changes to the B26,30 portion of insulin inhibiting formation of dimers and hexamers. They appear to improve postprandial glucose, incidence of hypoglycaemia and patient satisfaction and, when used in combination with basal insulin analogues, improve glycosylated haemoglobin in comparison to conventional insulin therapy. Additionally, they have been successfully used in children, pregnant women, in pump therapy and as part of premixed biphasic regimens. The two basal insulin analogues, glargine and detemir, developed by adjusting the isoelectric point and adding a fatty acid residue, respectively, have a protracted duration of action and a relatively smooth profile. Their pharmacokinetic and pharmacodynamic profiles have been assessed using euglycaemic clamp protocols. Both analogues have a longer duration of action, less of a peak of activity and a reduced variability with repeated injection. There is some evidence to suggest that detemir may have a slight hepatoselective effect. Clinical studies have shown a lower relative risk of hypoglycaemia and detemir appears to have a weight-sparing action. Insulin analogues represent a successful example of applied medical science. [source] Premixed insulin treatment for type 2 diabetes: analogue or human?DIABETES OBESITY & METABOLISM, Issue 5 2007Alan J. Garber The progressive nature of type 2 diabetes makes insulin initiation a necessary therapeutic step for many patients. Premixed insulin formulations containing both basal and prandial insulin (so called biphasic insulin) are often prescribed because they are superior to long- or intermediate-acting insulin in obtaining good metabolic control. In addition, they are considered as an attractive alternative to classical basal-bolus therapy as fewer daily injections are required. Premixed insulin formulations include conventional (e.g. biphasic human insulin 70/30, or 30/70 in European countries, BHI 30) and newer premixed human analogues (e.g. biphasic insulin aspart 70/30, or 30/70 in Europe, BIAsp 30; insulin lispro mix 75/25,Mix 75/25, or Mix 25/75 in Europe). Like conventional premixed human insulin, premixed insulin analogues contain a fixed proportion of soluble, rapid-acting insulin analogue, with protaminated analogue comprising the remainder. Unlike conventional premixes, analogue premixes have more physiological pharmacokinetic and therapeutically more desirable pharmacodynamic profiles than premixed human insulin. Consequently, postprandial glycaemic control is better with premixed insulin analogues than with premixed human insulin. In nontreat-to-target registration trials, the lowering of haemoglobin A1c with premixed insulin analogues was not inferior to that seen with premixed human insulin. Minor hypoglycaemia was similar for premixed analogue and premixed human insulins, while major hypoglycaemia appears to be rare with either formulation. The occurrence of adverse events, other than hypoglycaemia, was also similar between various premix insulins. The premixed insulin analogues, BIAsp 30 and Mix 75/25, like the fast-acting analogues from which they are derived, also allow flexible injection timing, relative to meal timing, thus improving adherence, compliance and quality of life compared with premixed human insulin. Overall, the evidence suggests that premixed insulin analogues are cost effective and have useful advantages over premixed human insulin for the treatment of type 2 diabetes. [source] Differential effects of short and long duration insulinotropic agents on meal-related glucose excursionsDIABETES OBESITY & METABOLISM, Issue 2 2001C. J. De Souza SUMMARY Aim Abnormal ,-cell function, characterized as the inability of the ,-cell to mount a rapid secretory response to glucose, is a well-established pathology of type 2 diabetes mellitus. These studies were designed to demonstrate the importance of early insulin release on the control of meal-induced glucose excursions by capitalizing on the significant pharmacodynamic differences between several oral insulin secreting agents. Methods Male Sprague Dawley fitted with indwelling jugular cannulas were used to compare the pharmacodynamic profiles of nateglinide (Nateg), glipizide (Glip) and repaglinide (Repag) through frequent blood samples following the administration of these compounds via oral gavage. In similar animals which were pretrained to consume their daily food intake in two discrete 45-min meals, the effects of compound induced changes in pre-meal, meal and post-meal insulin profiles on glycaemic control were assessed through frequent blood sampling following the administration of these compounds 10 min prior to a 30-min meal. Results There were significant pharmacodynamics differences between the three oral agents tested and the time to elicit peak insulin secretory responses increased from Nateg (4 min) to Repag (10 min) to Glip (45 min). During the meal tolerance test, glibenclamide did not increase pre-meal insulin levels and glucose excursions paralleled those in the control. Conversely, the other three agents, at doses that produced hypoglycaemic responses of similar magnitude, all increased early insulin release (,AUC(-15 to 3 min) = 0.5 ± 0.01, 1.6 ± 0.4, 3.6 ± 0.0, 1.2 ± 0.1 and 1.73 ± 0.4 nmol/min, for control, Nateg at 60 and 120 mg/kg, Glip and Repag, respectively) and curbed glucose excursions during the meal at varying rates and degrees (,AUC(0,30 min) = 39 ± 6, 8 ± 7, 5 ± 7, ,,1 ± 8 and ,,3 ± 8 mmol/min for control, Nateg at 60 and 120 mg/kg, Glip and Repag, respectively). However, unlike Nateg, the longer duration of action of Repag and Glip elicited sustained post-meal relative hypoglycaemia. Conclusion These data support the impact of early and rapid insulin release in the control of prandial and post-meal glycaemia and demonstrate that a short anticipatory burst of insulin, restricted to the beginning of a meal, provides a clear metabolic advantage and prevents post-meal hypoglycaemic episodes when compared to a greater but reactive insulin exposure that follows a meal-induced increase in glucose excursion. [source] | ||||||||||