The Experts below are selected from a list of 213 Experts worldwide ranked by ideXlab platform
A. Lucacchini - One of the best experts on this subject based on the ideXlab platform.
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Characterization of a voltage-dependent L-type calcium channel from rabbit and turtle brain
Neurochemical Research, 1996Co-Authors: B. Costa, L. Giusti, C. Martini, A. LucacchiniAbstract:The binding of [^3H]Nitrendipine to membrane preparation from turtle and rabbit brain was studied. A single population of [^3H]Nitrendipine binding sites was detected in both species. [^3H]Nitrendipine bound with high affinity to brain membrane from both rabbit and turtle, revealing a significant population of binding sites (K_ d values of 0.55±0.05 nM and 0.56±0.04 nM and B_max values of 122±11 and 275±18 fmol/mg of protein, respectively). Displacement studies showed a similar order of potency of various unlabeled ligands against [^3H]Nitrendipine both in rabbit or in turtle: Nitrendipine > nifedipine ≥ nicardipine ≫ verapamil ≥ diltiazem. Our results show that a two fold increment of [^3H]Nitrendipine binding sites exists in the turtle brain respect to the rabbit.
G Schwietzer - One of the best experts on this subject based on the ideXlab platform.
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combination treatment of enalapril with Nitrendipine in rats with renovascular hypertension
Hypertension, 1994Co-Authors: U O Wenzel, Udo Helmchen, W Schoeppe, G SchwietzerAbstract:We have recently shown that treatment with the calcium channel blocker Nitrendipine may aggravate albuminuria and glomerular injury in rats with two-kidney, one clip renovascular hypertension if arterial blood pressure is not reduced. To test whether Nitrendipine also exerts its adverse renal effects when normotension is achieved, we examined the effect of combined therapy with Nitrendipine and the converting enzyme inhibitor enalapril on blood pressure, albuminuria, glomerular filtration rate, and morphology of the nonclipped kidney. Rats treated with enalapril alone or in combination with the diuretic hydrochlorothiazide or rats treated with Nitrendipine alone served as controls. Therapy was started 6 weeks after clipping of one renal artery. Nitrendipine alone did not reduce blood pressure but significantly increased albuminuria, diuresis, glomerular filtration rate, and glomerular volume and injury compared with untreated hypertensive controls. Increase of glomerular filtration rate, diuresis, and albuminuria was reversible after withdrawal of Nitrendipine. Treatment with enalapril alone decreased blood pressure significantly but not to normotensive levels and was without significant effect on albuminuria and glomerular morphology. The combination of Nitrendipine and enalapril reduced blood pressure to normotensive levels and not only prevented the increase of glomerular volume, glomerular filtration rate, diuresis, and albuminuria caused by Nitrendipine alone but furthermore improved glomerular injury and albuminuria to levels not significantly different from normotensive controls. Enalapril in combination with the diuretic had similar beneficial effects on blood pressure, albuminuria, and glomerular injury. These data demonstrate that the adverse effects of Nitrendipine monotherapy on glomerular structure and function can be prevented by the combination of Nitrendipine and enalapril when blood pressure is normalized.
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adverse effect of the calcium channel blocker Nitrendipine on nephrosclerosis in rats with renovascular hypertension
Hypertension, 1992Co-Authors: U O Wenzel, Udo Helmchen, W Schoeppe, Gotz Troschau, G SchwietzerAbstract:The effect of a 6-week treatment with the calcium channel blocker Nitrendipine or the angiotensin converting enzyme inhibitor enalapril on blood pressure, albuminuria, renal hemodynamics, and morphology of the nonclipped kidney was studied in rats with two-kidney, one clip renovascular hypertension. Six weeks after clipping of one renal artery, hypertensive rats (178 +/- 4 mm Hg) were randomly assigned to three groups: untreated hypertensive controls (n = 8), enalapril-treated (n = 8), or Nitrendipine-treated (n = 10). Sham-operated rats served as normotensive controls (128 +/- 3 mm Hg, n = 8). After 6 weeks of treatment, renal hemodynamics (glomerular filtration rate and renal plasma flow) were measured in the anesthetized rats. Renal tissue was obtained for determination of glomerular size and sclerosis. Enalapril but not Nitrendipine reduced blood pressure significantly. After 6 weeks of therapy, glomerular filtration rate was not different among the studied groups. Renal plasma flow increased, but albumin excretion and glomerulosclerosis did not change after enalapril treatment. In contrast, in the Nitrendipine-treated group albuminuria increased from 12.8 +/- 2 progressively to 163 +/- 55 compared with 19.2 +/- 9 mg/24 hr in the hypertensive controls. Furthermore, glomerulosclerosis index was significantly increased in the Nitrendipine-treated group compared with the hypertensive controls (0.38 +/- 0.1 versus 0.13 +/- 0.04). In addition, glomerular size was higher in the Nitrendipine-treated group (14.9 +/- 0.17 10(-3) mm2) but lower in the enalapril-treated group (11.5 +/- 0.15 10(-3) mm2) compared with the hypertensive controls (12.1 +/- 0.17 10(-3) mm2).(ABSTRACT TRUNCATED AT 250 WORDS)
D D Breimer - One of the best experts on this subject based on the ideXlab platform.
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stereoselective pharmacokinetics of oral felodipine and Nitrendipine in healthy subjects correlation with nifedipine pharmacokinetics
European Journal of Clinical Pharmacology, 1993Co-Authors: P A Soons, T M T Mulders, Emi Uchida, H C Schoemaker, A F Cohen, D D BreimerAbstract:The pharmacokinetics of racemic (rac) felodipine, rac-Nitrendipine and nifedipine (all given as an oral dose of 20 mg in solution) have been investigated in a randomised cross-over study in 12 healthy male subjects using stereoselective assays. Both felodipine and Nitrendipine exhibited stereoselective pharmacokinetics. On average, the AUCs of the active (S)-enantiomers of felodipine and Nitrendipine were 139% and 104% higher than those of their optical antipodes, but the elimination half-lives of the enantiomers of each racemate were not different. The AUCs of nifedipine, rac-felodipine, rac-Nitrendipine and of their enantiomers were highly correlated (all r>0.83), suggesting closely related rate limiting steps in the in vivo first-pass metabolism of these high-clearance drugs. Stereoselectivity was only a minor contributor to inter-individual variability in the oral pharmacokinetics of these compounds in healthy subjects.
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stereoselective pharmacokinetics of oral and intravenous Nitrendipine in healthy male subjects
British Journal of Clinical Pharmacology, 1991Co-Authors: P A Soons, D D BreimerAbstract:Abstract 1. Stereoselectivity in the pharmacokinetics of Nitrendipine was investigated by reanalysing plasma samples of a previously published study (Soons et al., 1989). 2. Racemic Nitrendipine was administered intravenously (40 micrograms kg-1) and orally, both as plain tablet (20 mg) and in an osmotic pump device (40 mg Osmet) to nine healthy male subjects. Nitrendipine enantiomers were measured with a stereoselective assay. 3. Upon oral administration (tablet) the bioavailability of (S)-(-)-Nitrendipine (13.4% +/- 5.6%) was 75% (50% - 98%) higher than that of (R)-Nitrendipine (7.9% +/- 4.0%) (mean +/- s.d. (95% confidence interval)). Values of AUC and Cmax for (S)-Nitrendipine were 90% (55% - 121%) and 77% (51% - 100%) higher respectively, than those for (R)-Nitrendipine. Similar results were obtained with the osmotic system. 4. The clearance of intravenously administered (S)-Nitrendipine was slightly (7%) lower than that of (R)-Nitrendipine, but elimination half-lives and volumes of distribution were similar. 5. The difference in disposition of Nitrendipine enantiomers is most likely related to a difference in activity of the cytochrome P-450 system towards the enantiomers, giving rise to a two-fold difference in first-pass elimination. 6. Stereoselectivity in the first pass metabolism of Nitrendipine exhibited little intersubject variability and therefore is not a major factor in the wide variability in systemic availability of the more-potent (S)-enantiomer.
Venishetty Vinay Kumar - One of the best experts on this subject based on the ideXlab platform.
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development and evaluation of Nitrendipine loaded solid lipid nanoparticles influence of wax and glyceride lipids on plasma pharmacokinetics
International Journal of Pharmaceutics, 2007Co-Authors: Venishetty Vinay Kumar, Durairaj Chandrasekar, Sistla Ramakrishna, Veerabrahma Kishan, Prakash V DiwanAbstract:Nitrendipine is an antihypertensive drug with poor oral bioavailability ranging from 10 to 20% due to the first pass metabolism. For improving the oral bioavailability of Nitrendipine, Nitrendipine loaded solid lipid nanoparticles have been developed using triglyceride (tripalmitin), monoglyceride (glyceryl monostearate) and wax (cetyl palmitate). Poloxamer 188 was used as surfactant. Hot homogenization of melted lipids and aqueous phase followed by ultrasonication at temperature above the melting point of lipid was used to prepare SLN dispersions. SLN were characterized for particle size, zeta potential, entrapment efficiency and crystallinity of lipid and drug. In vitro release studies were performed in phosphate buffer of pH 6.8 using Franz diffusion cell. Pharmacokinetics of Nitrendipine loaded solid lipid nanoparticles after intraduodenal administration to conscious male Wistar rats was studied. Bioavailability of Nitrendipine was increased three- to four-fold after intraduodenal administration compared to that of Nitrendipine suspension. The obtained results are indicative of solid lipid nanoparticles as carriers for improving the bioavailability of lipophilic drugs such as Nitrendipine by minimizing first pass metabolism.
Prakash V Diwan - One of the best experts on this subject based on the ideXlab platform.
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development and evaluation of Nitrendipine loaded solid lipid nanoparticles influence of wax and glyceride lipids on plasma pharmacokinetics
International Journal of Pharmaceutics, 2007Co-Authors: Venishetty Vinay Kumar, Durairaj Chandrasekar, Sistla Ramakrishna, Veerabrahma Kishan, Prakash V DiwanAbstract:Nitrendipine is an antihypertensive drug with poor oral bioavailability ranging from 10 to 20% due to the first pass metabolism. For improving the oral bioavailability of Nitrendipine, Nitrendipine loaded solid lipid nanoparticles have been developed using triglyceride (tripalmitin), monoglyceride (glyceryl monostearate) and wax (cetyl palmitate). Poloxamer 188 was used as surfactant. Hot homogenization of melted lipids and aqueous phase followed by ultrasonication at temperature above the melting point of lipid was used to prepare SLN dispersions. SLN were characterized for particle size, zeta potential, entrapment efficiency and crystallinity of lipid and drug. In vitro release studies were performed in phosphate buffer of pH 6.8 using Franz diffusion cell. Pharmacokinetics of Nitrendipine loaded solid lipid nanoparticles after intraduodenal administration to conscious male Wistar rats was studied. Bioavailability of Nitrendipine was increased three- to four-fold after intraduodenal administration compared to that of Nitrendipine suspension. The obtained results are indicative of solid lipid nanoparticles as carriers for improving the bioavailability of lipophilic drugs such as Nitrendipine by minimizing first pass metabolism.
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development and validation of a reversed phase hplc method for determination of Nitrendipine in rat plasma application to pharmacokinetic studies
Biomedical Chromatography, 2007Co-Authors: Chandrasekar Durairaj, Vinay Kumar Venishetty, Ramakrishna Sistla, Madhusudhan Rao Yamsani, Prakash V DiwanAbstract:A simple and sensitive method for the determination of Nitrendipine in rat plasma was developed using high-performance liquid chromatography (HPLC). The procedure involves extraction of Nitrendipine in dichloromethane/sodium hydroxide, followed by reversed phase HPLC using a Waters, Spherisorb ODS2 (250 × 4.6 mm, 5 µm) column and UV detection at 238 nm. The retention times of Nitrendipine and internal standard (felodipine) were 5.0 min and 7.5 min, respectively. The calibration curves were linear over the range of 5 ng/mL (lower limit of quantification, LOQ) to 200 ng/mL for Nitrendipine. The intra- and inter-day coefficients of variation for all criteria of validation were less than 15% over the linearity range. The sensitivity and precision of the method were within the accepted limits (< 15%) throughout the validation period. The present method was also successfully applied for the study of plasma pharmacokinetics of Nitrendipine loaded solid lipid nanoparticles (SLN) in rats. Copyright © 2007 John Wiley & Sons, Ltd.