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排序方式: 共有1103条查询结果,搜索用时 15 毫秒
1.
G. Toffoli I. Robieux D. Fantin M. Gigante S. Frustaci G. L. Nicolosi M. De Cicco & M. Boiocchi 《British journal of clinical pharmacology》1997,44(3):255-260
Aims In an attempt to reverse multidrug resistance, in a recent trial of verapamil in association with doxorubicin, we used escalating doses of continuous intravenous (i.v.) verapamil under close haemodynamic monitoring. We report the pharmacokinetics of escalating doses of verapamil.
Methods We studied nine patients [
seven males, two females; median age 46 years (range, 31–57)] with advanced adenocarcinoma of the colon and normal renal, hepatic, and cardiac functions. After a loading dose (0.15 mg kg−1 followed by 12 h continuous i.v. infusion at 0.20 mg kg−1 h−1 ), the infusion rate (ko) of verapamil was increased every 24 h (0.25, 0.30, 0.35, and 0.40 mg kg−1 h−1 ). The highest rate was maintained for 48 h. Doxorubicin was given as a continuous i.v. infusion from 12 to 108 h (n=4) or 60 to 108 h (n=5). Blood samples and urine collections were taken every 12 h. Verapamil and nor-verapamil were assayed by high performance liquid chromatography. We calculated systemic clearance of verapamil (CL=ko/Css ) and renal clearance (CLr) of verapamil and nor-verapamil. The Cssvs rate relationship was fitted to a Michaelis-Menten equation: Css=ko(Km+Css )/(V Vm ).
Results CL was dose-dependent and in all nine patients a significant reduction in CL was observed over the dose range (mean CL±s.d. were 0.51±0.31, 0.38±0.16, 0.32±0.18, and 0.27±0.11 l h−1 kg−1, respectively, at 0.25, 0.30, 0.35, and 0.40 mg kg−1 h−1; P=0.0001). Css increased more than proportionally to the dose rate and the Cssvs rate relationship was best defined by a Michaelis-Menten equation (Km=730 μg l−1; V Vm=0.55 mg kg−1 h−1 ), (r=0.994; P=0.006). CLr of verapamil and nor-verapamil was not saturable but the contribution to the elimination was only 2 to 4% of the dose.
Conclusions These findings suggest a non-linear, capacity-limited metabolic clearance of high-dose verapamil. Using escalating infusion rates, high verapamil concentrations (1500–2500 ng ml−1 ) were achieved without major toxicity. Saturable clearance may cause higher bioavailability and slower elimination of verapamil after acute oral overdoses. 相似文献
2.
Alain Djacoba Tehindrazanarivelo Jean Marc Visy Marie-Germaine Bousser 《Cephalalgia : an international journal of headache》1992,12(5):318-320
We report two patients with ipsilateral attacks of cluster headache and chronic paroxysmal hemicrania. The first patient, a 33-year-old man, started having attacks of chronic cluster headache at the age of 27. At 33, they were replaced by typical attacks of ipsilateral chronic paroxysmal hemicrania which showed a dramatic improvement with indomethacin 150 mg daily. After two days of complete remission, cluster headache attacks reappeared and persisted until verapamil, 360 mg a day, was added to indomethacin. The second patient, a 45-year-old man, first developed attacks of episodic cluster headache at the age of 35. At 44, he experienced ipsilateral typical attacks of chronic paroxysmal hemicrania, and two months later attacks of cluster headache. Under verapamil 240 mg daily, attacks of cluster headache disappeared, but those of chronic paroxysmal hemicrania increased in frequency until indomethacin 150 mg daily was added. These observations suggest a close relationship but not a similarity between cluster headache and chronic paraoxysmal hemicrania, and show the practical therapeutic interest of maintaining this distinction. 相似文献
3.
M. Vincenzi T. Morlino P. Allegri E. Barbieri F. Cappelletti U. Delio R. Ometto P. Maiolino 《Clinical cardiology》1981,4(1):15-21
Alterations in cardiovascular function induced by the acute intravenous administration of verapamil (5 or 10 mg) in 52 patients (29 with ischemic heart disease and 23 without heart disease) were evaluated with use of invasive techniques (right and left heart catheterization, left ventricular cineangiography, and coronary arteriography). The most significant changes were represented by a decrease in systemic vascular resistance and systemic arterial pressure, and an increase in heart rate and cardiac output. Contractility indexes were not depressed in either group, and altered ventricular wall motion tended to improve to a slightly smaller degree than in patients treated with nitroglycerin. The use of verapamil in patients with ischemic heart disease appears to be safe, and concern about the negative inotropic influences in humans no longer seems justified. 相似文献
4.
甲基黄酮醇胺盐酸盐对异丙肾上腺素正性频率作用的影响 总被引:2,自引:0,他引:2
本文比较了甲基黄酮醇胺盐酸盐(MFOA)、普萘洛尔(Pro)、维拉帕米(Ver)对异丙肾上腺素(Iso)所致兔离体右心房正性频率作用的影响。Pro使Iso累积浓度反应曲线平行右移,不抑制最大反应,属于典型的竞争性抑制剂,其pA2=8.43;MFOA和Ver使Iso量效曲线向下右移,抑制最大反应,为非竞争性拮抗。MFOA(2×10~(-5)M)和Ver(2×10~(-7)M)分别使最大反应下降19.28%和48.57%,其pD'2值分别为4.07±0.14、6.68±0.15。结果表明MFOA的作用不同于Pro,和Ver相似。 相似文献
5.
The effects of quercetin have been investigated on the gastrointestinal propulsion of charcoal meal in mice. Quercetin reduced the rate of intestinal transit and this effect was potentiated by verapamil. 相似文献
6.
Lothar SCHRAMM Josef ZIMMERMANN Kai LOPAU Hong LING Joachim HARLOS Ekkehart HEIDBREDER 《Nephrology (Carlton, Vic.)》1995,1(3):241-250
Summary: Calcium channel blockers are able to improve renal function in acute renal failure (ARF) and natriuretic peptides can also exert beneficial effects. At present it is unknown whether administration of atrial natriuretic peptide (ANP) and a calcium channel blocker given before a toxic lesion can prevent gentamicin induced ARF. the mechanisms of action of natriuretic peptides and calcium channel blockers are different and, as yet, it has not been clarified if combined administration can augment the effects on renal function. After a basal period we investigated the effects of verapamil (VER, 0.66 mg/kg), ANP, (30 μg/kg) and a combination of both (identical doses as described individually). the drugs were given intravenously for a period of 40 min (infusion period) before gentamicin (15 mg/kg, i.v.) was administered for induction of ARF. Basal values for glomerular filtration rate (GFR, mL/min) were around 1.8 with no differences between the groups. At the end of the infusion period (before application of gentamicin) GFR was significantly elevated with VER + ANP (3.13 ± 0.51), ANP (2.70 ± 0.59) and VER (2.34 ± 0.47) compared to controls (saline, 1.7 ± 0.48). After application of gentamicin GFR significantly dropped in the control group (0.77 ± 0.21, 0.75 ± 0.19, respectively), indicating development of ARF. In contrast with VER + ANP, ANP and VER GFR could be maintained for 30 min (2.47 ± 0.39, 2.28 ± 0.33, 2.22 ± 0.43, respectively) and 130 min (2.11 ± 0.32, 1.86 ± 0.29, 2.11 ± 0.28, respectively) after gentamicin. Moreover ANP and VER revealed natriuretic activity and, due to their vasorelaxing potency, also influenced arterial blood pressure. We conclude that both VER and ANP are able to prevent early gentamicin induced ARF when given before the toxic lesion. Both drugs induce hyperfiltration while infused, in particular when administered in combination. 相似文献
7.
G. N. Kryzhanovskii V. K. Reshetnyak M. L. Kukushkin M. P. Gorizontova V. S. Smirnova 《Bulletin of experimental biology and medicine》1992,114(3):1217-1220
Laboratory of Pathophysiology of Pain and Laboratory of General Pathology of the Microcirculation, Research Institute of General Pathology and Pathological Physiology, Russian Academy of Medical Sciences, Moscow. Translated from Byulleten' Éksperimental'noi Biologii i Meditsiny, Vol. 114, No. 9, pp. 229–231, September, 1992. 相似文献
8.
M. Ocaña E. Del Pozo R. Carlos J. M. Baeyens 《Journal of neural transmission (Vienna, Austria : 1996)》1992,88(3):223-234
Summary The effects of several calcium antagonists (verapamil, nicardipine and two diltiazem isomers, d-cis and l-cis diltiazem) alone and associated to non-depolarizing (pancuronium) and depolarizing (succinylcholine) neuromuscular blockers, were evaluated on sciatic nerve-tibialis anterior muscle preparations from cats in vivo. The calcium antagonists used (at 0.1 and 0.5mg/kg iv) did not modify the height of muscular twitches elicited indirectly. However, these agents potentiated in a dose-dependent way the neuromuscular blockade induced by iv pancuronium (2–40g/kg) and succinylcholine (6–200g/kg). The order of potency in increasing the effects of pancuronium was nicardipine d-cis diltiazem verapamil, whereas the order of potency in enhancing succinylcholine effects was d-cis diltiazem verapamil nicardipine. The effects of diltiazem were stereoselective, thus the potentiation induced by d-cis diltiazem was significantly greater in all cases than that induced by l-cis diltiazem, which suggests that calcium channel blockade plays a role in these interactions. However, other mechanisms such as calcium antagonists-induced nicotinic receptor desensitization may also be involved. 相似文献
9.
T T Chen T A Lane M C Doody M R Caudle 《American journal of reproductive immunology (New York, N.Y. : 1989)》1992,28(1):43-50
Macrophages and their secretory products, cytokines, play an integral role in many reproductive processes. In this study we examined the effect of conditioned media from cultured human peritoneal macrophages on progesterone production by granulosa cells and the role of calcium in this process. Macrophages were pretreated with various concentrations of a calcium channel blocker (verapamil) or a calcium ionophore (A23187). Macrophage-conditioned media (MCM) or cell-free media that contained calcium channel modifiers were added at three dose levels to cultured porcine granulosa cells. Progesterone production and LH receptor content were determined. Macrophage-conditioned media alone elevated basal progesterone production, but significantly attenuated granulosa cell LH receptor content. These effects were neither potentiated nor suppressed by pretreating macrophages with verapamil. However, production of the LH receptor lowering factor(s) appeared to be suppressed by calcium ionophore. We conclude that (1) one or more factors produced by macrophages have a net stimulatory effect on basal progesterone production and these factor(s) may not be calcium-dependent and (2) macrophage-derived secretory products reduce granulosa cell LH receptor content. The production of these factor(s) may be calcium-dependent. 相似文献
10.
YESIM TUNCOK SEBNEM APAYDIN SULE KALKAN MEHMET ATES & HULYA GUVEN 《International journal of experimental pathology》1996,77(5):207-212
The goal of this study was to compare the effects of glucagon and amrinone on mean arterial pressure (MAP) and heart rate, when used alone and in combination, in an anaesthetized rat model of verapamil toxicity. Rats were anaesthetized and the carotid artery was cannulated for MAP and heart rate measurements. Jugular and femoral veins were cannulated for drug administration. After verapamil infusion (15 mg/kg/h), control animals were given normal saline solution and the other groups received amrinone (0.1 or 0.2 mg/kg/min), glucagon (0.3 mg/kg bolus followed by 0.1 or 0.2 mg/kg/min infusion), glucagon plus amrinone (0.1 mg/kg/min and 0.1 mg/kg/min respectively) or glucagon plus amrinone (0.2 mg/kg/min and 0.1 mg/kg/min respectively). Glucagon (0.2 mg/kg/min) significantly increased MAP when compared to the control group ( P < 0.01). The combination of glucagon and amrinone did not produce a synergistic effect for the recovery of MAP. Furthermore, this combination masked the positive effects of glucagon (0.2 mg/kg/min) on MAP.Glucagon (0.2 mg/kg/min) increased the heart rates compared with those of the control group ( P < 0.05). Additionally, amrinone (0.1 mg/kg/min) plus glucagon (0.1 mg/kg/min) increased the heart rates ( P < 0.05). Finally, glucagon dose dependently recovered MAP. While amrinone depressed MAP in combination with glucagon, it did not alter the positive chronotropic effect of high dose glucagon. 相似文献