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1.
Ashish Verma Vijay K. Vanguri Venkata Golla Sean Rhyee Matthew Trainor Konstantin Abramov 《Journal of medical toxicology》2013,9(1):71-74
Introduction
Sodium hypochlorite is the active ingredient in bleach, a ubiquitous household disinfectant, and has known toxicities depending on route of exposure and amount. Acute kidney injury due to sodium hypochlorite exposure has never been reported. Patients that did develop nephrotoxicity following bleach exposure did so due to development of other risk factors for kidney injury such as volume depletion or sepsis.Discussion
We report a patient who presented with black urine after parenteral self-administration of a large quantity of bleach. We review the clinical presentation, laboratory and biopsy findings, and outcome as well as discuss possible mechanisms of sodium hypochlorite toxicity and management strategies. 相似文献2.
A. P. Cossu M. Musu P. Mura L. M. De Giudici G. Finco 《European journal of clinical pharmacology》2014,70(1):23-28
Purpose
Thrombocytopenia is a common complication in the intensive care unit (ICU), but the incidence of drug-induced thrombocytopenia (DIT) is not well defined. We investigate linezolid-induced thrombocytopenia in patients with impaired renal function. Since recent studies suggest that linezolid clearance is reduced in these patients and there are no precise data confirming that dose-adjustment should be required, we performed a systematic analysis in order to establish whether it is necessary to consider a dose adjustment and promote studies to confirm this concept.Methods
We report a case of thrombocytopenia (nadir 32?×?103/μl) in a patient with acute kidney injury who was treated with linezolid for a MRSA pulmonary infection. We performed a systematic review of the literature through PubMed with the aim to include every case report, case series, prospective and retrospective clinical study reporting linezolid-induced thrombocytopenia with concomitant impaired renal function.Results
An increasing number of clinical studies suggest a correlation between the onset of linezolid-induced thrombocytopenia and renal dysfunction. Close monitoring of platelet count and hemoglobin is recommended in patients treated with linezolid, especially in those with impaired renal function because the reduction of its clearance causes drug accumulation, as some studies have reported.Conclusions
Clinicians should consider the potential risk of this complication, especially in elderly patients with end-stage renal disease. Further studies should be encouraged to determine if the incidence of linezolid-related thrombocytopenia could be reduced by a dose adjustment according to renal function, for which currently there is still no specific recommendation. 相似文献3.
Hesamoddin Hosseinjani Azadeh Moghaddas Hossein Khalili 《European journal of clinical pharmacology》2013,69(7):1375-1390
Purpose
To review available evidence on the effectiveness of N-acetylcysteine (NAC) as a prophylactic agent in the prevention of non-contrast media agent-induced kidney injury.Method
Data were collected by searching Scopus, PubMed, Medline, Science direct and Cochrane database systematic reviews. A total of 26 relevant experimental studies up to the date of publication were included in the review.Results
Available evidence shows that NAC has the potential to exert significant protective or ameliorative effects against drug-induced kidney injury in experimental models. The possible suggested renoprotective mechanisms of NAC in different experimental settings were acting as an antioxidant by restoring the pool of intracellular reduced glutathione, scavenging of free radicals, and/or interacting with reactive oxygen species.Conclusion
Whether the administration of NAC could be an effective protective clinical strategy to prevent drug-induced kidney injury or not is a question that remains to be answered in future clinical trials. 相似文献4.
Background
CCl4 is a well-established hepatotoxin inducing liver injury by producing free radicals. Exposure to CCl4 also induces acute and chronic renal injuries. The present study was designed to establish the protective effect of hesperidin (HDN), a citrus bioflavonoid, on CCl4-induced oxidative stress and resultant dysfunction of rat liver and kidney.Methods
Animals were pretreated with HDN (100 and 200 mg/kg orally) for one week and then challenged with CCl4 (2 ml/kg/s.c.) in olive oil. Rats were sacrificed by carotid bleeding under ether anesthesia. Liver enzymes, urea and creatinine were estimated in serum. Oxidative stress in liver and kidney tissue was estimated using Thiobarbituric acid reactive substances (TBARS), glutathione (GSH) content, superoxide dismutase(SOD), and Catalase (CAT)Results
CCl4 caused a marked rise in serum levels of ALT and AST (P < 0.05). TBARS levels were significantly increased whereas GSH, SOD and CAT levels decreased in the liver and kidney homogenates of CCl4 treated rats. HDN (200 mg/kg) successfully attenuated these effects of CCl4Conclusion
In conclusion, our study demonstrated a protective effect of HDN in CCl4 induced oxidative stress in rat liver and kidney. This protective effect of HDN can be correlated to its direct antioxidant effect. 相似文献5.
Manjusha Abraham Lowell Tilzer K. Sarah Hoehn Stephen L. Thornton 《Journal of medical toxicology》2015,11(3):364-367
Introduction
The brown recluse spider (BRS) (Loxosceles reclusa) envenomation can lead to multiple complications, including hemolysis. We present a case of refractory hemolysis after a BRS bite treated with therapeutic plasma exchange (TPE).Case Report
A 17-year-old female presented with fever, fatigue, and dyspnea. She was diagnosed with sepsis and received intravenous (IV) fluids, inotropic support, and antibiotics. On hospital day 1 she was noted to have skin lesion consistent with a BRS bite and developed hemolysis. Systemic loxoscelism with hemolysis was then suspected and methylprednisolone IV was initiated. She was discharged with a stable HGB on hospital day 3 on oral prednisolone. She was re-admitted 24 h later, with signs of worsening hemolysis. Methylprednisolone was restarted and she was transfused 4 units of packed red blood cells. TPE was initiated due to the refractory hemolysis. Shortly after the TPE session, her clinical and laboratory status improved. She required no further transfusions and was discharged on a steroid taper.Discussion
TPE is an extra-corporeal method to remove substances from the blood by separating plasma from cellular blood components and replacing it with physiologic fluids. TPE has been used for snake envenomation but there are no reports detailing its use for BRS envenomations. Improvement was associated with TPE initiation and may have been due to removal of complement components activated by the spider venom. This report suggests that TPE could be a possible treatment modality for systemic loxoscelism with refractory hemolysis due to BRS envenomation. Further investigation is warranted. 相似文献6.
Wolfgang Domej Heike Mitterhammer Rudolf Stauber Peter Kaufmann Karl Heinz Smolle 《Journal of medical toxicology》2007,3(4):173-177
Introduction
Gasoline, ingested intentionally or accidentally, is toxic. The majority of reported cases of gasoline intoxication involve oral ingestion or inhalation. Data are scarce on complications and outcomes following hydrocarbon poisoning by intravenous injection.Case Report
Following a suicide attempt by intravenous self-injection of 10 ml of gasoline, a 26-year-old medical student was admitted to the intensive care unit (ICU) with hemoptysis, symptoms of acute respiratory failure, chest pain, and severe abdominal cramps. Gas exchange was severely impaired and a chest x-ray indicated chemical pneumonitis. Initial treatment consisted of mechanical ventilation, supportive hyperventilation, administration of nitrogen oxide (NO), and prednisone. Unfortunately, the patient developed multi-organ dysfunction syndrome (MODS) complicated by life-threatening severe vasoplegia within 24 hours after gasoline injection. High doses of vasopressors along with massive amounts of parenteral fluids were necessary. Despite fluid replacement, renal function worsened and required hemofiltration on 5 sequential days. After 12 days of intensive care management, the patient recovered completely and was discharged to a psychiatric care facility.Discussion
Intravenous gasoline injection causes major injury to the lungs, the organ bearing the first capillary bed encountered. Treatment of gasoline poisoning is symptomatic because no specific antidote is available. Early and aggressive supportive care may be conducive to a favorable outcome with minimal residual pulmonary sequelae. 相似文献7.
Qi Liu Changyuan Wang Qiang Meng Xiaokui Huo Huijun Sun Jinyong Peng Xiaochi Ma Pengyuan Sun Kexin Liu 《Pharmaceutical research》2014,31(5):1120-1132
Purpose
To conduct in vivo and in vitro experiments to investigate puerarin (PUR), an isoflavone C-glyoside, and elucidate its ability to alter methotrexate (MTX) transport and pharmacokinetics.Methods
In vivo absorption studies, in vitro everted intestinal sac preparation, kidney slices in rats and bi-directional transport assay with mock-/MDCK-MDR1 cells, uptake studies in HEK293-OAT1/3 cells were employed to evaluate the interaction.Results
In vivo and in vitro MTX absorption in rats were enhanced in combination with PUR. PUR inhibited digoxin efflux transport in MDCK-MDR1 monolayers with an IC50 value of 1.6?±?0.3 μM, suggesting that the first target of drug interaction was MDR1 in the intestine during the absorption process. MTX renal clearance decreased significantly after simultaneous intravenous administration. MTX uptake in rat kidney slices and HEK293-OAT1/3 cells were markedly inhibited by PUR, suggesting that the second target of drug interaction was OATs located in the kidney. Moreover, concomitant administration of PUR reduced renal MTX accumulation and plasma levels of creatinine and BUN.Conclusions
Co-administration of PUR enhanced MTX exposure by inhibition of intestinal MDR1 and renal OAT1/3. Although the renal damage of MTX was improved by PUR, the high level exposure of MTX should be cautious in the clinical usage. 相似文献8.
Purpose
To elucidate the effect of sterols on the aggregation of amphotericin B (AmB) in PEG-phospholipid micelles and its consequences on the hemolytic activity of AmB.Methods
AmB-incorporated PEG-phospholipid micelles co-loaded with ergosterol, cholesterol, or 7-dehydrocholesterol were prepared at 4:1:1 and 20:5:1 ratios of polymer-to-sterol-to-AmB. The aggregation state of AmB was elucidated by UV?Cvis spectroscopy. AmB/sterol co-loaded PEG-phospholipid micelles were incubated with red blood cells and the hemolytic activity of AmB assessed by measurement of free hemoglobin.Results
AmB in PEG-phospholipid micelles stayed mostly in a deaggregated state in the absence of sterol or with cholesterol, but aggregated in the presence of ergosterol or 7-dehydrocholesterol. The fraction of aggregated AmB in PEG-phospholipid micelles was lower at the 20:5:1 ratio. In an aggregated state or in the absence of sterol, AmB caused rapid and complete hemolysis. In contrast, deaggregated AmB co-loaded with cholesterol caused slower and incomplete hemolysis, especially at a 20:5:1 ratio.Conclusions
The aggregation state of AmB in PEG-phospholipid micelles was sterol dependant. AmB/cholesterol co-loaded PEG-phospholipid micelles caused low in vitro hemolysis due to deaggregation of AmB and micellar stability, presumably owing to cholesterol/phospholipid versus cholesterol/AmB interactions in the interior core region. 相似文献9.
Nadav Willner Shimon Storch Tamar Tadmor Elad Schiff 《European journal of clinical pharmacology》2014,70(3):261-263
Background
Methotrexate (MTX), an antimetabolite of folic acid, is the drug of choice for the nonsurgical management of ectopic pregnancy. MTX-related toxicity may include leukopenia, thrombocytopenia, pancytopenia, nausea, vomiting, stomatitis, mucositis, and liver and lung toxicity, depending primarily on the dosage of the drug and patients' renal function. Currently, the use of MTX in hemodialysis patients, even at a low dosage, is controversial, and no clear-cut guidelines are available.Case report
We report here a rare case of a life-threatening complication characterized by severe pancytopenia and skin and mucosal injury, which developed in a young patient on hemodialysis after oral treatment with MTX for ectopic pregnancy.Conclusion
We conclude that even low-dose MTX administration is not to be used in patients with renal insufficiency, and when no other therapeutic options are available we suggest taking several clinical measures to prevent or treat myelosuppression. 相似文献10.
11.
Koji Kato Haruyuki Mori Tomoko Kito Miyu Yokochi Sumito Ito Katsuhisa Inoue Atsushi Yonezawa Toshiya Katsura Yuji Kumagai Hiroaki Yuasa Yoshinori Moriyama Ken-ichi Inui Hiroyuki Kusuhara Yuichi Sugiyama 《Pharmaceutical research》2014,31(1):136-147
Purpose
Multidrug and toxin extrusion proteins (MATEs) are multispecific organic cation transporters mediating the efflux of various cationic drugs into the urine. The present study aimed at identifying endogenous compounds in human plasma and urine specimens as biomarkers to evaluate drug interactions involving MATEs in the kidney without administration of their exogenous probe drugs.Methods
An untargeted metabolomic analysis was performed using urine and plasma samples from healthy volunteers and mice treated with or without the potent MATE inhibitor, pyrimethamine. Plasma and urinary concentrations of candidate markers were measured using liquid chromatography-mass spectrometry. Transport activities were determined in MATE- or OCT2-expressing HEK293 cells. The deuterium-labeled compounds of candidates were administered to mice for pharmacokinetics study.Results
Urinary excretion of eleven compounds including thiamine and carnitine was significantly lower in the pyrimethamine-treatment group in humans and mice, whereas no endogenous compound was noticeably accumulated in the plasma. The renal clearance of thiamine and carnitine was decreased by 70%–84% and 90%–94% (p?<?0.05), respectively, in human. The specific uptake of thiamine was observed in MATE1-, MATE2-K- or OCT2-expressing HEK293 cells with Km of 3.5?±?1.0, 3.9?±?0.8 and 59.9?±?6.7 μM, respectively. The renal clearance of carnitine-d 3 was decreased by 62% in mice treated with pyrimethamine.Conclusions
Our findings indicate that MATEs account for the efflux of thiamine and perhaps carnitine as well as drugs into the urine. The urinary excretion of thiamine is useful to detect drug interaction involving MATEs in the kidney. 相似文献12.
George M. Bosse Melissa A. Platt Stephen D. Anderson Michael W. Presley 《Journal of medical toxicology》2011,7(1):52-56
Introduction
Hyperkalemia is a common condition, particularly in the setting of renal dysfunction. Hyperkalemia due to intentional oral potassium overdose is not commonly reported.Case Report
We present a case of acute intentional potassium overdose in a patient with normal renal function resulting in significant hyperkalemia, with a maximum serum potassium concentration of 11 mEq/L. Despite an initial course complicated by various unstable cardiac rhythms, including ventricular tachycardia, ventricular fibrillation, and pulseless electrical activity, the patient was discharged from the hospital neurologically intact. Treatment for hyperkalemia included hemodialysis.Discussion
The role of dialysis in potassium overdose is poorly defined.Conclusion
Based on this case and a review of the medical literature, we recommend hemodialysis for cases of potassium overdose with hemodynamic instability and significantly elevated serum potassium concentrations that do not respond promptly to medical therapy. Hemodialysis should also be considered in cases with underlying renal dysfunction. 相似文献13.
Andrejs Skesters T. Zvagule A. Silova N. Rusakova L. Larmane J. Reste M. Eglite K. D. Rainsford B. A. Callingham M.-A. Bake A. Lece 《Inflammopharmacology》2010,18(1):17-23
Aims
To establish if there is further evidence for the long-term oxidant stress injury (as reported previously—Kumerova et al. in Biol Trace Elem Res 77:1–12, 2000) in surviving Chernobyl nuclear power plant (NPP) workers from Latvia. The overall objectives of this study have been to establish if there have been long-term systemic changes in the oxidant/antioxidant status of clean-up workers that might reflect adaptation to the progression of oxidative stress injury.Methods
Biochemical analyses of the circulating levels of endogenous oxidants and anti-oxidants were undertaken over two periods (Stage 1 in 1998–1999 and Stage 2 in 2005–2006) at approximately 6–7 years time interval, in order to establish if there have been time-dependent changes in the parameters that may be important for the health of the clean-up workers. The biochemical analyses included (a) plasma levels of the anti-oxidant, selenium, (b) blood and plasma levels of glutathione peroxidase, (c) red blood cell catalase, (d) plasma total oxidant status as lipid peroxides and hydroperoxides, (e) plasma ceruloplasmin, and (f) total blood levels of zinc and copper.Results
The circulating content of lipid peroxides, plasma oxidisability, lipid peroxides, catalase, Zn, and Cu were elevated above normal values at both the stages of this study. Glutathione peroxidase was increased above normal values at Stage 1 but not at Stage 2. The most pronounced changes between Stage 1 and Stage 2 were (a) a reduction by about ½ in the content of lipid peroxides and lipid peroxidation, but not in the blood oxidisability and (b) increased plasma selenium. The data show that there may be a partial improvement in the anti-oxidant/oxidant status of the Chernobyl NPP workers over the 7-year period of investigation.Conclusions
The NPP patients may be undergoing progressive reduction in blood oxidants accompanied by adaptation to oxidant stress injury due to the increased anti-oxidant activity measured in their plasma and blood. 相似文献14.
Carlos Alberto León-Espinoza Silviu Bordu Javier Lopez-Sebastian Elena Muñoz-Forner Francisco Morera-Ocón Luis Sabater-Orti Bruno Camps-Vilata Joaquin Ortega-Serrano 《Central European Journal of Medicine》2014,9(4):588-593
Background
Since the Atlanta Symposium several guidelines and consensus conferences have been published to improve the management and understanding of patients with acute pancreatitis. Herein, a review of the most recent guidelines on acute pancreatitis is carried out, trying to find differences and similarities.Methods
Five of the last international guidelines on acute pancreatitis as well as the last consensus conference are critically reviewed.Conclusions
There is more consensus than disagreement between guidelines, which is why the knowledge of them is of great importance when treating AP. 相似文献15.
Ken-ichi Fujita Tomoko Sugiura Hidenori Okumura Saki Umeda Noritaka Nakamichi Yusuke Watanabe Hiromichi Suzuki Yu Sunakawa Ken Shimada Kaori Kawara Yasutsuna Sasaki Yukio Kato 《Pharmaceutical research》2014,31(1):204-215
Purpose
Clinical study has previously revealed that plasma concentration of 7-ethyl-10-hydroxycamptothecin (SN-38), an active metabolite of irinotecan, was higher in patients with end-stage renal failure than those with normal kidney function although SN-38 is mainly eliminated in the liver. Here, we focused on inhibition by uremic toxins of hepatic SN-38 uptake and down-regulation of uptake transporter(s) by uremic plasma in humans.Methods
We evaluated SN-38 uptake and its inhibition by uremic toxins, 3-carboxy-4-methyl-5-propyl-2-furanpropionate (CMPF), indoxyl sulfate (Indox), hippuric acid (HA) and indole acetate (IA), with cryopreserved human hepatocytes and HEK293 cells stably expressing hepatic uptake transporters, organic anion transporting polypeptides (OATPs). We also collected plasma samples from patients with severe renal failure to examine their effects on mRNA level of OATPs in primary cultured human hepatocytes.Results
SN-38 was taken up by hepatocytes, which showed biphasic saturation patterns. The SN-38 uptake by hepatocytes was significantly inhibited by a uremic toxin mixture including clinically relevant concentrations of CMPF, Indox, HA and IA. Kinetic analyses for OATP-mediated transport revealed that the uptake of SN-38 by OATP1B1 was the highest, followed by OATP1B3. Among the uremic toxins, CMPF exhibited most potent inhibition of OATP1B1-mediated SN-38 uptake and directly inhibited the uptake of SN-38 also in hepatocytes. In addition, gene expression of OATP1B1 and OATP1B3 in hepatocytes was significantly down-regulated by the treatment with the uremic plasma.Conclusions
OATP1B1-mediated hepatic uptake of SN-38 was inhibited by uremic toxins, and gene expression of OATP1B1 was down-regulated by uremic plasma. 相似文献16.
Purpose
In the renal proximal tubular cells, various transporters play important roles in the secretion and reabsorption of drugs. When metabolic acidosis is induced, a number of adaptive changes occur in the kidney. The purpose of this study was to clarify the changes of drug transporters under the acidosis and the effects of these changes on urinary drug excretion.Methods
Wistar/ST rats were given 1.5% NH4Cl in tap water for 48 h to induce the acidosis. Pharmacokinetics of PSP or metformin was evaluated. In addition, expression levels of drug transporters were examined by Western Blotting.Results
The renal clearance of PSP was markedly decreased, whereas the creatinine clearance and renal clearance of metformin were unchanged. Furthermore, Western blots indicated that the protein expression level of organic anion transporter (OAT) 3 was decreased. In contrast to OAT3 levels, OAT1 and organic cation transporter (OCT) 2 levels were unaffected. An immunohistochemical analysis showed that the OAT3 protein in the proximal tubules was localized in the basolateral membrane both of the normal and the acidosis rats.Conclusion
The decrease of renal excretion of anionic drugs during metabolic acidosis might be partly due to a reduction in the level of OAT3 protein. 相似文献17.
Background
In India, Curcumin (CMN) is popularly known as "Haldi", and has been well studied due to its economic importance. Traditional Indian medicine claims the use of its powder against biliary disorders, anorexia, coryza, cough, diabetic wounds, hepatic disorder, rheumatism and sinusitis. This study was designed to examine the possible beneficial effect of CMN in preventing the acute renal failure and related oxidative stress caused by chronic administration of cyclosporine (CsA) in rats. CMN was administered concurrently with CsA (20 mg/kg/day s.c) for 21 days. Oxidative stress in kidney tissue homogenates was estimated using thiobarbituric acid reactive substances (TBARS), reduced glutathione (GSH) content, superoxide dismutase (SOD), and Catalase (CAT). Nitrite levels were estimated in serum and tissue homogenates.Results
CsA administration for 21 days produced elevated levels of TBARS and marked depletion of renal endogenous antioxidant enzymes and deteriorated the renal function as assessed by increased serum creatinine, Blood Urea Nitrogen (BUN) and decreased creatinine and urea clearance as compared to vehicle treated rats. CMN markedly reduced elevated levels of TBARS, significantly attenuated renal dysfunction increased the levels of antioxidant enzymes in CsA treated rats and normalized the altered renal morphology.Conclusion
In conclusion our study showed that CMN through its antioxidant activity effectively salvaged CsA nephrotoxicity. 相似文献18.
Song Y Xue W Tian P Ding X Pan X Yan H Hou J Feng X Xiang H Tian X Qin G Fan X 《European journal of clinical pharmacology》2011,67(6):553-562
Objective
The effects of diltiazem on 1692 kidney transplant recipients under the immunosuppressive regimen of cyclosporine A (CsA) in combination with either mycophenolate mofetil or azothioprine were assessed. The two treatment groups were compared for blood concentrations of CsA, the extent of acceptable dosage reduction for the maintenance of immunotherapy, potential effects of kidney protection, and promotion of graft function.Method
We monitored changes of blood concentrations of CsA in the two different patient treatment groups for post-transplant graft function, episodes of acute rejection, and hepatic and renal toxicity in 1640 renal transplant recipients after treatment with diltiazem.Results
In patients treated with the triple immunosuppressive regimen consisting of CsA, azothioprine, and prednisolone (Pred), the sub-group of patients receiving the diltiazem treatment saw a significantly reduced CsA dosage in comparison to the non-diltiazem group (control group 1) (P?<?0.05), but the blood concentrations of CsA of the diltiazem group were higher than those of control group 1 (P?<?0.01). Of the patients treated with CsA, mycophenolate mofetil, and Pred, the sub-group of patients also treated with diltiazem showed similar effects: CsA dosage was reduced (P?<?0.01) and the blood concentrations of CsA significantly increased (P?<?0.01) in comparison with those of control group 2. In addition, recovery time of graft function decreased to 4.7?±?1.8?days and 3.9?±?1.4?days in the two diltiazem treatment groups, respectively (P?<?0.05), and the rate of acute rejection decreased to 21 (p?<?0.05) and 7.9% (P?<?0.01), respectively.Conclusion
In our cohort of renal transplantation patients, co-administration of CsA and diltiazem increased CsA blood concentration, thereby resulting in a reduction in its required dosage treatment, which lightened the patients?? economic burden while improving primary and long-term kidney function by promoting the recovery of graft function and decreasing hepatic and renal toxicity. The co-administration of diltiazem may also reduce the rate of acute rejection, especially in patients who also receive the triple immunosuppressive regimen consisting of CsA, mycophenolate mofetil, and Pred. 相似文献19.
Cai J Huang Z Yang G Cheng K Ye Q Ming Y Zuo X Zhou P Yuan H 《Am J Cardiovasc Drugs》2011,11(6):401-409
Background
Hypertension, a major complication in kidney transplant recipients, is associated with premature death and graft loss. However, an optimal antihypertensive therapy for these patients has not been established [Chinese Clinical Trial Registry No. ChiCTR-TRC-10001071].Objective
The aim of the present study was to evaluate the effect of amlodipine and valsartan on BP control in renal transplant patients and to analyze the correlation between cytochrome P450 (CYP) 3A5 or multidrug resistance-1 gene (MDR1) genotype and the antihypertensive effect of these two regimens.Methods
150 renal transplant patients with stage 1 or 2 hypertension were enrolled in the trial. Patients were randomly assigned to amlodipine or valsartan. Metoprolol was added if BP was not under control after 4 weeks. BP and plasma levels of ciclosporin were monitored during the 24-week trial. CYP3A5 and MDR1 genotypes were determined using a polymerase chain reaction-restriction fragment length polymorphism (PCR-RFLP) method.Results
The demographic features and baseline BP were similar between these two groups. During the 24-week trial, the reduction of systolic BP (SBP) was similar between the amlodipine and valsartan groups. However, the reduction of diastolic BP (DBP) was significantly greater in the amlodipine group compared with the valsartan group at 12, 16, and 24 weeks of treatment. The plasma level of ciclosporin at 2 hours of medication was significantly higher in the amlodipine group than in the valsartan group after 4 weeks of the trial. The reduction of DBP at 24 weeks was greater in the subjects with CYP3A5 *3/*3 variant than in those with CYP3A5*1/*1 variant (?13.5± 1.9mmHg vs ?8.7± 1.6mmHg, p<0.05).Conclusion
The present study demonstrated that amlodipine produced a greater reduction of DBP than valsartan, although both amlodipine and valsartan resulted in satisfactory control of BP in patients with renal transplantation. Administration of amlodipine significantly increased the plasma concentration of ciclosporin, and its effects on BP control and ciclosporin concentration may be associated with the CYP3A5 genotype in these subjects [Chinese Clinical Trial Registry No. ChiCTR-TRC-10001071]. 相似文献20.
Alma Idrizi Myftar Barbullushi Arben Beqiri Liri Hoxha Alketa Koroshi Nereida Spahia Margarita Gjata Xhoana Xhaferri Valbona Bajrami Nestor Thereska 《Central European Journal of Medicine》2013,8(3):335-338