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Increasing Dosage (increasing + dosage)
Selected AbstractsOn the ropivacaine-reducing effect of low-dose sufentanil in intrathecal labor analgesiaACTA ANAESTHESIOLOGICA SCANDINAVICA, Issue 8 2010C. M. ORTNER Background: Combining ropivacaine with sufentanil for intrathecal (i.t.) analgesia in labor is well recognized, but information on dosing is limited. This study aimed to determine the ED 50 of i.t. ropivacaine and to assess the effect of adding defined low doses of sufentanil. Methods: This was a two-phase, double-blind, randomized and prospective study. One hundred and fifteen parturients receiving combined spinal epidural analgesia were allocated to one of four groups to receive ropivacaine or sufentanil alone or in combination. In phase one, sufentanil dose,response was calculated using logistic regression. In phase two, ED 50 of ropivacaine and of the combination with a fixed dosage of sufentanil at ED 20 and ED 40 was evaluated using the technique of up,down sequential allocation. Analgesic effectiveness was assessed 15 min after injection using a 100 mm visual analog scale, with <10 mm lasting for 45 min defined as effective. Furthermore, side effects and duration were recorded. Results: The ED 50 of i.t. ropivacaine was 4.6 mg [95% confidence intervals (95% CI) 4.28, 5.31]. Adding sufentanil at ED 20 significantly decreased the ED 50 of i.t. ropivacaine to 2.1 mg (95%CI 1.75, 2.5) (P<0.005); at ED 40, the reduction was similar (P<0.005). Combining sufentanil with ropivacaine resulted in a dose-independent prolongation of analgesia. Besides pruritus, which was well tolerated, there were no differences in side effects. Conclusion: Adding sufentanil at ED 20 results in a more than 50% dose-sparing effect of ropivacaine and considerably prolongs analgesia. Increasing dosage implicates no clinical benefit. [source] ,Pseudo-aldosteronism' induced by intravenous glycyrrhizin treatment of chronic hepatitis C patientsJOURNAL OF GASTROENTEROLOGY AND HEPATOLOGY, Issue 7 2001Tekla GJ Van Rossum Abstract Background and Aims: Treatment with intravenous glycyrrhizin reduces the progression of liver disease caused by chronic hepatitis C (HCV) infection. Glycyrrhetinic acid, a metabolite of glycyrrhizin, inhibits the renal conversion of cortisol to cortisone by inhibiting the enzyme 11,-hydroxysteroiddehydrogenase in the kidney. The resulting excess of cortisol subsequently stimulates the mineralocorticoid receptor, leading to pseudo-aldosteronism with hypertension, hypokalemia and eventually renin and aldosterone suppression. The aim of this study was to evaluate the occurrence of pseudo-aldosteronism after treatment of chronic hepatitis C (HCV) patients with increasing doses of intravenous glycyrrhizin. Methods: Forty-four HCV patients with chronic hepatitis or compensated cirrhosis were treated with intravenous glycyrrhizin 6 × 200 mg/week, 3 × 240 mg/week or 3 × 0 mg/week (placebo) for 4 weeks. In all patients, bodyweight, blood pressure and plasma concentrations of sodium, potassium, cortisol, DHEA-S (dehydroepiandrosterone sulfate), renin and aldosterone were measured before, and at 0 and 4 weeks after treatment. Results: Within the placebo group, no significant changes were observed. Within the 1200 mg group systolic blood pressure was significantly higher at the end of treatment, while aldosterone was significantly lower; at the end of the follow-up period these values had returned to baseline. The changes from baseline in systolic and diastolic blood pressure at the end of treatment were significantly higher in the 1200 mg group compared to the placebo group. The changes in aldosterone and potassium concentrations at the end of treatment increased with increasing dosage, although not significantly. Conclusion: Hepatitis C virus patients with chronic hepatitis or compensated cirrhosis show minor reversible symptoms of pseudo-aldosteronism after treatment with 1200 mg glycyrrhizin weekly for 4 weeks. [source] Dose-dependent pharmacokinetics of a new neuroprotective agent for ischemia-reperfusion damage, KR-31378, in ratsBIOPHARMACEUTICS AND DRUG DISPOSITION, Issue 7 2000Hee J. Kim Abstract The dose-dependent pharmacokinetic parameters of a new neuroprotective agent for ischemia-reperfusion damage, KR-31378, were evaluated after intravenous and oral administration, 10, 20, and 50 mg/kg, to rats. After intravenous administration of 50 mg/kg, the dose-normalized (10 mg/kg) AUC (994 µg min/mL) was significantly greater than that at 10 (569 µg min/ml) and 20 (660 µg min/mL) mg/kg. This could be due to slower clearance (Cl) with increasing dosage (18.5, 14.6, and 10.2 mL/min/kg for 10, 20, and 50 mg/kg, respectively). The slower Cl with increasing dosage could be due to saturable metabolism of KR-31378 in rats and this could be supported by significantly slower Clnr and significantly greater 24-h urinary excretion of the drug at 50 mg/kg than those at 10 and 20 mg/kg. After oral administration of 50 mg/kg, the dose-normalized (10 mg/kg) AUC (1160 µg min/mL) was significantly greater than that at 10 (572 µg min/mL) and 20 (786 µg min/mL) mg/kg. Note that the AUCs were comparable (not significantly different) between intravenous and oral administration at each dosage, indicating that the absorption from gastrointestinal tract was almost complete and the first-pass (gastric, intestinal, and hepatic) effect was not considerable after oral administration to rats. Copyright © 2000 John Wiley & Sons, Ltd. [source] Improving lipid management , to titrate, combine or switchINTERNATIONAL JOURNAL OF CLINICAL PRACTICE, Issue 7 2004H. Schuster Summary Despite the benefits of statin therapy, cholesterol management remains suboptimal and many patients do not achieve their recommended low-density lipoprotein cholesterol (LDL-C) goals. The use of insufficient doses, limited drug effectiveness and poor patient compliance may contribute to the treatment gap. Options for improving lipid management include dose titration, combination therapy or prescribing a more efficacious statin. LDL-C reductions are generally modest when patients' current statin dose is titrated, and there may be an increased potential for adverse effects. Combining statin therapy with another lipid-modifying agent can provide additional LDL-C reductions, but cost, tolerability and compliance should be considered. In general, switching to a more efficacious statin is a cost-effective way of enabling more patients to achieve recommended targets without increasing dosages. When considering the options available, physicians should balance efficacy, cost and safety to enable more patients to attain LDL-C goals and achieve greater therapeutic gain from statin treatment. [source] Stringent testing identifies highly potent and escape-proof anti-HIV short hairpin RNAsTHE JOURNAL OF GENE MEDICINE, Issue 6 2009Karin J. von Eije Abstract Background RNA interference (RNAi) is a cellular mechanism that can be induced by small interfering RNAs to mediate sequence-specific gene silencing by cleavage of the targeted mRNA. RNAi can be used as an antiviral approach to silence the human immunodeficiency virus type 1 (HIV-1) through stable expression of short hairpin RNAs (shRNAs). Previously, we used a co-transfection assay in which shRNA constructs were transfected with an HIV-1 molecular clone to identify 20 shRNA inhibitors that target highly conserved HIV-1 sequences. Methods In the present study, we selected the most potent shRNAs to formulate a combinatorial shRNA therapy and determine the best and easiest method for antiviral shRNA selection. We performed transient inhibition assays with either a luciferase reporter or HIV-1 molecular clone and also infected shRNA-expressing T cell lines with HIV-1 and monitored virus replication. The latter assay allows detection of viral escape. In addition, we also tested shRNA-expressing T cells upon challenge with increasing dosages of HIV-1, and measured the dose required to result in massive virus-induced syncytia formation in this 2-week assay. Results Extended culturing selected three highly effective shRNAs that do not allow viral replication for more than 100 days. This difference in potency was not observed in the transient co-transfection assays. The use of increased dosages of HIV-1 selected the same highly potent shRNAs as the laborious and extended escape study. Conclusions These highly potent shRNAs could be used for a clinical vector and the comparison of the developed assays might help other researchers in their search for antiviral shRNAs. Copyright © 2009 John Wiley & Sons, Ltd. [source] | ||||||||||