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Biological Half-life (biological + half-life)
Selected AbstractsFunction of a long-term, GLP-1-treated, insulin-secreting cell line is improved by preventing DPP IV-mediated degradation of GLP-1DIABETES OBESITY & METABOLISM, Issue 5 2005B. D. Green Glucagon-like peptide-1 (GLP-1) is an important insulinotropic hormone with potential in the treatment of type 2 diabetes. However, the short biological half-life of the peptide after cleavage by dipeptidylpeptidase IV (DPP IV) is a major limitation. Inhibition of DPP IV activity and the development of resistant GLP-1 analogues is the subject of ongoing research. In this study, we determined cell growth, insulin content, insulin accumulation and insulin secretory function of a insulin-secreting cell line cultured for 3 days with either GLP-1, GLP-1 plus the DPP IV inhibitor diprotin A (DPA) or stable N -acetyl-GLP-1. Native GLP-1 was rapidly degraded by DPP IV during culture with accumulation of the inactive metabolite GLP-1(9,36)amide. Inclusion of DPA or use of the DPP IV-resistant analogue, N -acetyl-GLP-1, improved cellular function compared to exposure to GLP-1 alone. Most notably, basal and accumulated insulin secretion was enhanced, and glucose responsiveness was improved. However, prolonged GLP-1 treatment resulted in GLP-1 receptor desensitization regardless of DPP IV status. The results indicate that prevention of DPP IV action is necessary for beneficial effects of GLP-1 on pancreatic , cells and that prolonged exposure to GLP-1(9,36)amide may be detrimental to insulin secretory function. These observations also support the ongoing development of DPP-IV-resistant forms of GLP-1, such as N -acetyl-GLP-1. [source] Developmental and Therapeutic Pharmacology of Antiepileptic DrugsEPILEPSIA, Issue 2000Hisao Miura Summary: We investigated the clinical effects and plasma levels of zonisamide (ZNS) in children with cryptogenic localization-related epilepsies. ZNS is absorbed slowly from the gastrointestinal tract, and its biological half-life is long as compared with that of other common antiepileptic drugs. The peak-to-trough plasma level ratios during a day were as small as 1.28 ± 0.15 in children taking a daily dose of 8 mg/kg of ZNS once a day as a single drug. The plasma level (,g/ml) to dose (mg/kg/day) ratios estimated by the trough and peak plasma levels both increased with advancing age, but the peak-to-trough plasma level ratios were maintained almost uniformly throughout the pediatric age period. A wide range of the plasma levels was associated with complete freedom from seizures. The range of the plasma levels in patients who did not respond to ZNS was higher than that in the controlled group. However, the clinical effects of ZNS were in agreement with the range of generally accepted therapeutic plasma levels of ZNS, 15,40 ,g/ml. Any patient who receives polytherapy is at risk to develop 1 or more drug interactions. Concurrent administration of carbamazepine (CBZ) decreases plasma concentrations of ZNS. However, ZNS does not alter plasma concentrations of CBZ or its primary metabolite, carbamazepine-10,11-epoxide (CBZ-E). It is evident that the concurrent administration of lamotrigine (LTG) affects plasma concentrations of CBZ-E, while plasma CBZ levels remain unaltered. However, the effect of LTG on plasma concentrations of CBZ-E is small, and none of the study patients showed toxic plasma concentrations of CBZ-E or associated clinical toxicity. Drug-protein binding interactions are another source of side effects. A simultaneous administration of valproic acid increases the total plasma CBZ-E levels relative to the CBZ dose associated with the raised free fractions of CBZ and CBZ-E. The high free plasma concentrations of CBZ-E above 1.5 ,g/ml may be responsible for the side effects. [source] Pharmacoeconomics of factor dosing in the haemophilia populationHAEMOPHILIA, Issue 2006E. BERNTORP Summary., Treatment of haemophilia is extremely costly due to the short biological half-life of infused factor and pricing issues. This paper examines the impact of different dosing schedules on factor consumption, via a review of literature on dosing regimens used for prophylaxis with a focus on pharmacokinetics (PK). Pharmacokinetics were found to have an important role for pharmacoeconomics in factor dosing both for assessment of the treatment and for developing new treatment protocols but the clinical response to treatment must always guide the dosing schedule. In order to better understand pharmacoeconomics during prophylaxis, controlled prospective studies are needed but much can also be learned from studies of existing cohorts that have been treated for decades. [source] Higher 25-hydroxyvitamin D is associated with lower relapse risk in multiple sclerosis,ANNALS OF NEUROLOGY, Issue 2 2010Steve Simpson Jr. MPH Objective A protective association between higher vitamin D levels and the onset of multiple sclerosis (MS) has been demonstrated; however, its role in modulating MS clinical course has been little studied. We investigated whether higher levels of serum 25-hydroxyvitamin D (25-OH-D) were associated with a lower risk of relapses in people with MS. Methods We conducted a prospective cohort study of 145 participants with relapsing-remitting MS from 2002 to 2005. Serum 25-OH-D levels were measured biannually, and the hazard of relapse was assessed using survival analysis. Results There was an inverse linear relationship between 25-OH-D levels and the hazard of relapse over the subsequent 6 months, with hazard ratio (HR) 0.91 (95% confidence interval [CI]: 0.85,0.97) per 10nmol/l increase in 25-OH-D level (p = 0.006). When variation due to timing of blood collection was removed by estimating 25-OH-D at the start of each season, this association persisted, with HR 0.90 (95% CI, 0.83,0.98) per 10nmol/l increase (p = 0.016). Taking into account the biological half-life of 25-OH-D, we estimated 25-OH-D at monthly intervals, resulting in a slightly enhanced association, with HR 0.88 (95% CI, 0.82,0.95) per 10nmol/l increase (p = 0.001). Adjusting for potential confounders did not alter these findings. Interpretation In this prospective population-based cohort study, in a cohort largely on immunomodulatory therapy, higher 25-OH-D levels were associated with a reduced hazard of relapse. This occurred in a dose-dependent linear fashion, with each 10nmol/l increase in 25-OH-D resulting in up to a 12% reduction in risk of relapse. Clinically, raising 25-OH-D levels by 50nmol/l could halve the hazard of a relapse. ANN NEUROL 2010;68:193,203 [source] Effects of dietary squid viscera meal on growth and cadmium accumulation in tissues of Japanese seabass, Lateolabrax japonicus (Cuvier 1828)AQUACULTURE RESEARCH, Issue 11 2006Kangsen Mai Abstract Cadmium (Cd) is a toxic environmental pollutant with a long biological half-life and can produce both hepatic and renal injuries in mammals and fish. Squid viscera meal (SVM), an effective attractant for aquatic animals, is widely used as an ingredient in aquafeeds. However, SVM is rich in Cd and its complexes. A study was conducted to evaluate the effects of dietary SVM on the growth and Cd deposition in tissues of Japanese seabass, Lateolabrax japonicus. Three practical diets were formulated to contain 0, 50 and 100 g SVM kg,1 diet, respectively, containing 0.21, 7.26 and 12.08 mg Cd kg,1 diet. Each diet was randomly assigned to triplicate groups of 80 Japanese seabass (mean initial weight, 10.89±0.21 g) in floating sea cages (1.5 × 1.5 × 2.0 m). Fish were fed twice daily (06:30 and 16:30 hours) to satiation for 8 weeks. The results showed that there were no significant differences in fish survival among three dietary treatments, but significant higher specific growth rates (SGR) were observed in the fish fed diets with 50 or 100 g SVM kg,1 diet than that from the control group (P<0.05). The Cd concentrations in the kidney, liver and gill were found in a decreasing order at each treatment, and positively correlated with dietary Cd levels. Fish fed diets with 50 and 100 g SVM kg,1 diet had significantly higher Cd accumulations in the kidney (3.25, 5.85 mg kg,1), liver (0.76, 1.26 mg kg,1) and gill (0.42, 0.58 mg kg,1) compared with the control group (0.82, 0.34 and 0.32 mg kg,1 respectively) (P<0.05). The Cd concentration in fish muscle; however, was undetectable in any treatment. Therefore, based on these results, accumulation of Cd in edible tissue (muscle) of farmed Japanese seabass is not a food safety issue. However, long-term feeding of diets with SVM may result in accumulation of Cd in the kidneys, liver and gills of fish. [source] | ||||||||||