伊马替尼联合粒细胞集落刺激因子治疗慢性粒细胞白血病11例

目的 研究伊马替尼(IM)联合粒细胞集落刺激因子(G-CSF)降低单药IM疗效欠佳的慢性粒细胞白血病(CML)残留病的疗效.方法 采用IM联合G-CSF治疗11例IM治疗后Ph染色体转阴率≥35%的CML患者.起始治疗量为IM 400或600 mg/d,G-CSF 5μg·kg-1·d-1,皮下注射.白细胞计数≥30×109/L者,延迟或间断使用G-CSF直至白细胞＜20×109/L.治疗过程中定期检测外周血bcr-abl转录水平,治疗6个月后转录水平降低未超过0.5个对数(log)者,停用G-CSF.bcr-abl转录水平持续下降但仍未获得完全分子生物学缓解者,继续使用该方案治疗1～6个月.结果 11例患者中9例出现bcr-abl转录水平的明显下降(包括7例下降＞1个对数和2例下降＞0.5个对数),2例出现bcr-abl转录水平的下降小于0.5个对数.7例下降＞1个对数者,其中2例获得完全分子生物学缓解,5例原为部分细胞遗传学缓解的患者获得完全细胞遗传学缓解.所有患者均能耐受,未出现因不良反应中断治疗和治疗相关性死亡病例.结论 IM联合G-CSF方案治疗单药lM治疗反应欠佳的CML患者有效、安全.     

bcr-abl mRNA检测在慢性粒细胞白血病诊治中的意义

目的 探讨bcr-abl mRNA在慢性粒细胞白血病(CML)诊断、治疗及微小残留病变监测中的意义.方法 采用实时定量聚合酶链反应(real-time PCR)方法检测324例CML患者518份标本的bcr-abl mRNA表达情况.结果 CML慢性期、加速期和急变期患者的bcr-abl mRNA定量结果逐渐增高,分别为12.6%、25.4%和57.2%(P<0.05).异基因造血干细胞移植后的bcr-abl mRNA定量结果随时间延长逐渐降低,一般在移植6个月后转阴,服用伊马替尼(商品名:格列卫)与异基因造血干细胞移植病程相似,但融合基因转阴所用时间较长.结论 real-time PCR检测bcr-abl mRNA对于诊断、评价疗效、监测微小残留病变以及预测疾病进展具有重要的临床应用价值.     

急性白血病患者静脉注射高剂量阿糖胞苷后血浆阿糖胞苷、阿糖尿苷、细胞内三磷酸阿糖胞苷浓度测定和影响因素分析

目的 检测急性白血病患者静脉注射高剂量阿糖胞苷(Ara-C)后血浆、阿糖尿苷(Ara-U)和细胞内三磷酸阿糖胞苷(Ara-CTP)浓度,对不同Ara-C给药剂量和细胞内外药物浓度间的关系及影响因素进行分析研究.方法 提取75例急性白血病患者首剂静脉注射不同剂量Ara-C(分别为0.5、1.0、2.0g/m2)后单个核细胞和血清,采用不同色谱条件进行反相高效液相色谱法(RP-HPLC)分析.结果 细胞内Ara-CTP检测质量浓度在0.28～18.96μg/ml范围内线性关系良好(r=0.998),检测限为0.28μg/ml;血浆Ara-C和Ara-U的检测限分别为0.0157和1.034μg/ml;27例样本的保存时间超过1.5年,其中11例血浆Ara-C浓度低于检测限(40.7%),36例样本的单个核细胞数＜1.5×106/ml,其中15例细胞内Ara-CTP浓度低于检测限(41.7%);血浆Ara-U和细胞内Ara-CTP浓度随给药剂量增加而增高,血浆Ara-C浓度未随给药剂量增加而增高;年龄＞40岁患者的细胞内Ara-CTP浓度有随年龄增长而增加的趋势.结论 RP-HPLC法用于Ara-C血药浓度和细胞内Ara-CTP水平测定简便、稳定、重复性好.在Ara-C0.5～2.0 g/m2剂量范围内,血浆Ara-U和细胞内Ara-CTP浓度随给药剂量增加而增高.     

沙利度胺治疗急性白血病的疗效及对血管调控因子水平的影响

目的 观察沙利度胺联合化疗治疗急性白血病的临床疗效及其对血浆血管内皮生长因子(VEGF)、血管内皮生长因子受体(VEGFR)、碱性成纤维细胞生长因子(bFGF)水平的影响.方法 急性白血病患者36例,随机分为试验组及对照组各18例.每组均予以常规化疗方案标准剂量化疗,试验组同时口服沙利度胺100 mg/d.治疗前及治疗后8周分别采集外周血,双抗体夹心酶联免疫吸附法(ELISA)检测血浆VEGF、VEGFR、bFGF含量.以15位健康体检者为健康对照组.结果 试验组与对照组有效率分别为88.9%(16/18)和77.8%(14/18),差异有统计学意义(x2=4.103,P＜0.05).试验组与对照组治疗前血浆VEGF水平分别为(389.78±249.94)和(318.54±125.78)pg/ml,高于健康组的(132.91±26.66)pg/ml(t=3.141、3.024,均P＜0.01);治疗后分别为(211.74±36.72)和(288.02±31.77)pg/ml,高于健康组(t=2.413、2.324,均P＜0.05);试验组与对照组治疗前VEGF差异无统计学意义(t=1.384,P＞0.05),治疗后差异有统计学意义(t=2.793,P＜0.05).试验组与对照组治疗前血浆VEGFR水平分别为(2490.75±1695.9)和(2322.78±1105.87)pg/ml,高于健康组的(1134.98±378.45)pg/ml(t=2.914、2.783,均P＜0.01);治疗后分别为(1359.71±390.24)和(1753.89±337.04)pg/ml,与健康组相比差异有统计学意义(t=2.572、2.447,均P＜0.05);试验组与对照组治疗前VEGFR差异无统计学意义(t=1.276,P＞0.05),治疗后差异有统计学意义(t=2.486,P＜0.05).试验组与对照组治疗前血浆bFGF水平分别为(2.43±0.27)和(2.4l±0.33)ng/ml,高于健康组的(1.83±0.44)ng/ml(t=4.982、4.171,均P＜0.05);治疗后分别为(2.09±0.17)和(2.11±0.31)ng/ml,与健康组相比差异有统计学意义(t=3.01l、2.773,均P＜0.05);试验组与对照组治疗前及治疗后相比差异无统计学意义(t=0.953、1.282,均P＞0.05).结论 沙利度胺联合化疗可提高急性白血病患者的缓解率,有可能成为一种通过抗血管新生从而抑制白血病细胞生长及浸润的有效治疗方法.     

bcr-abll激酶抑制剂耐药突变研究及治疗进展:第52届美国血液学年会的热点问题

伊马替尼(Imatinib)是人工设计的一种酪氨酸激酶抑制剂(tyrosine kinase inhibitor,TKI),由于其出色的临床疗效,很快成为慢性粒细胞白血病(CML)的一线治疗药物.     

低剂量硼替佐米联合沙利度胺及化疗治疗多发性骨髓瘤35例

目的 观察低剂量硼替佐米联合沙利度胺及化疗治疗多发性骨髓瘤(MM)患者的疗效及安全性.方法 35例初治及难治复发MM患者,硼替佐米1.1 mg/m2,第0、3、7、10天,静脉注射;沙利度胺从50 mg/d开始逐渐加量至150 mg/d或患者能够耐受的最大剂量;化疗方案根据每疗程患者情况选择MP、VAD或AD方案.28 d为1个疗程,每例患者至少接受2个疗程以上治疗.达到部分缓解(PR)及以上疗效的患者应用沙利度胺150 mg/d或患者能够耐受的最大剂量维持治疗.采用2006年MM国际统一疗效标准观察疗效,根据国际癌症研究中心不良事件通用命名标准评估不良反应.结果 中位随访20个月,35例患者治疗总有效率82.8%,其中完全缓解(CR)率48.6%,良好的部分缓解(VGPR)率17.1%,PR率17.1%.3年预计无进展生存(PFS)和总生存(OS)率分别为60.92%和72.41%.达PR以上疗效患者的OS率高于未达PR患者,差异有统计学意义(P=0.004).初治及难治复发患者客观缓解率(ORR)及OS率差异无统计学意义.Ⅲ～Ⅳ度非血液学毒性主要包括乏力(3/35)、恶心、呕吐(8/35)、便秘(4/35)和周围神经病变(3/35).Ⅲ～Ⅳ度血液学毒性为粒细胞缺乏(10/35)和血小板减少(8/35).结论 低剂量硼替佐米联合沙利度胺及化疗治疗MM具有较好的疗效及安全性,沙利度胺维持治疗可延长患者PFS时间.     

异基因造血干细胞移植在慢性粒细胞白血病治疗中仍有一定地位

慢性粒细胞白血病(CML)是成年人常见的白血病,我国CML的年发病率稍低于西方国家.对CML的治疗而言,酪氨酸激酶抑制剂(TKI)--伊马替尼(imatinb mesylate,IM)的问世是继白消安(myleran,busulfan)、羟基脲(hydroxyurea)、干扰素(IFN-α)、异基因造血干细胞移植(allo-BMT)之后的又一个新的里程碑[1].IM对CML的治疗取得了卓越的治疗效果,其对初治的慢性期CML血液学的缓解率达90%以上,细胞遗传学缓解率可达80%以上,甚至部分病例可获得分子学的缓解(CMoR)[2-3].     

环氧化酶-2抑制剂对功能性鼻内镜手术后血浆及术野渗液前列腺素E2的作用

目的:外科手术引起的炎性反应会影响患者预后,本随机对照研究拟检验功能性鼻内镜手术后术野渗液和血浆前列腺素E2(prostaglandin E2,PGE2)的变化以及与疼痛及预后的相关性.方法:37名准备在全身麻醉下行功能性鼻内镜手术的患者被随机分为两组,塞来昔布组(n=16)术前1 h口服塞来昔布400 mg,术后连续5 d口服塞来昔布200 mg,q12 h;对照组(n=21)不服药.术后即刻到术后48 h收集鼻腔术野渗液并采集静脉血测量PGE2浓度,同时测量血浆中血栓烷素A2(thromboxane A2,TXA2)和前列环素(prostacyclin,PGI2)的浓度.结果:功能性鼻内镜手术后,对照组术野渗液和血浆PGE2水平显著升高,分别在术后6 h(177.5±142.2ng/L)和48 h(64.5±21.4 ng/L)达到高峰.塞来昔布组出现术野渗液PGE2水平(术后6 h达到高峰,106.2±33.4 ng/L)和血浆PGE2水平(术后48 h达到高峰,44.7±30.2 ng/L)显著下降(P＜0.05).术后疼痛视觉模拟评分(VAS)与术野渗液的PGE2水平呈正相关,术后6 h和48 h相关系数分别为0.333(P=0.044)和0.353(P=0.032).塞来昔布对TXA2/PGI2比值无影响.结论:外科手术部位PGE2水平升高是手术后炎症反应的重要表现,并参与引起术后疼痛;环氧化酶-2抑制剂可以显著抑制外周和血浆PGE2水平.     

非洛地平联合依那普利治疗原发性高血压临床观察

目的:观察非洛地平联合依那普利治疗原发性高血压的临床疗效.方法:所有患者治疗前停服降压药2 w.非洛地平+依那普利组服用非洛地平缓释剂5mg/d,依那普利10 mg/d,均1次/d.非洛地平组单服用非洛地平缓释剂5mg/d,1次/d,疗程均为4 w.服药2w后,如血压达到130/80mmHg以下,或收缩压(SBP)下降20mmHg,或舒张压(DBP)下降10mmHg,则继续服药;反之则增加药物剂量,非洛地平增至10mg/d,依那普利增至20mg/d.结果:治疗4w后,非洛地平+依那普利组SBP/DBP下降[(18.42+16.85)/(15.26+13.62)mmHg]明显高于非洛地平组[(12.13+9.05)/(10.97+8.18)mmHg](P＜0.05).非洛地平+依那普利组显效34例,有效14例;非洛地平组显效19例,有效21例;非洛地平+依那普利组总有效率(96.0%)显著高于非洛地平组(80.0%)(P＜0.05).治疗前后两组患者心率、肝功能、血脂、血糖无异常变化.结论:非洛地平联合依那普利具有良好的协同降低血压的效果,副作用小,安全有效.     

应用LSI9q34探针及ES/DCDF探针检测慢性粒细胞白血病患者der(9)缺失的研究

目的 研究慢性粒细胞性白血病(CML)患者衍生9号染色体[der(9)]部分序列缺失情况,探讨LSI 9q34探针在检测der(9)缺失中的联合应用价值.方法 对52例CML患者采用不加任何刺激剂的骨髓进行24 h短期培养法制备染色体,吉姆萨显带进行核型分析.应用ES/DCDF探针及LSI 9q34探针对骨髓间期细胞进行荧光原位杂交,并检测der(9)部分序列缺失.结果 52例中经ES/DCDF探针检测全部为ber-abl融合基因阳性,其中12例患者伴有der(9)部分缺失,占23.0%,经LSI 9q34探针检测有11例患者伴有der(9)部分缺失.结论 LSI9q34探针在判断CML患者是否伴有der(9)缺失方面有较好的特异性.伴有缺失的患者疾病进展较快,预后较差,甲磺酸依马替尼治疗不能完全逆转其负性作用,建议所有bcr-abl融合基因阳性的CML患者均应行 LSI 9q34探针检测,以指导临床治疗.     

Estimating the prevalence of delayed median nerve conduction in the general population

In a double-blind, randomized, crossover study of 25 patients after abdominal aortic surgery, we compared patient-controlled analgesia (PCA) with epidural versus intravenous pethidine. All patients received continuous epidural infusions of 0.125% bupivacaine adjusted to maintain appropriate sensory levels. The 48 hour study period commenced 36 to 48 hours after surgery and covered postoperative days 2 and 3. There was a crossover in PCA mode (epidural or intravenous) after 24 hours. Plasma pethidine concentration at the end of each 24 hour period and the total 24 hour pethidine dose did not change significantly between postoperative days 2 and 3. Pethidine plasma concentration was lower after 24 hours epidural than after intravenous PCA [125 (SD 108) ng/ml versus 171 (SD 107) ng/ml, P = 0.03], although pethidine dose did not differ significantly [mean 147 (SD 124) mg/24 h]. Visual analog pain scores (VAS) did not differ significantly between postoperative days 2 and 3, or at rest between epidural and i.v. groups. However, VAS with coughing and with abdominal palpation were lower in the epidural PCA group (P = 0.05, 0.008). With a background epidural infusion of 0.125% bupivacaine, PCA with epidural pethidine provided better pain control than PCA intravenous pethidine and this was achieved at lower plasma pethidine concentrations.     

Antifungal prophylaxis with itraconazole in neutropenic patients with acute leukaemia

The efficacy of antifungal prophylaxis with itraconazole capsules and its serum concentrations were evaluated in patients intensively treated for acute leukaemia. A consecutive group of patients without systemic antifungal prophylaxis (January 1993 to August 1994, period 1) was compared with another consecutive group of patients (period 2) who received itraconazole capsules (September 1994 to April 1995 400 mg/day, from May 1995 onwards 600 mg/day). All patients admitted with acute leukaemia and standard or high-dose chemotherapy were included into the study. Clinical endpoint was mortality from proven fungal infection. Seventy-six patients and 148 courses of cytotoxic chemotherapy were analysed in the control group as well as 47 patients and 112 treatment courses in the intervention group. Antifungal prophylaxis led to a significant decrease of mortality from invasive fungal infections (8.8%-0.9%, P = 0.005). The median trough concentration of itraconazole of all measurements was 520 ng/ml (range 230-793) in patients who received 400 mg/day and 760 ng/ml (370-1200) in patients receiving a dosage of 600 mg/day (P = 0.002). These findings suggest that itraconazole is an effective drug for antifungal prophylaxis but also that a considerable number of patients do not reach the desired trough levels (>500 ng/ml) with itraconazole capsules.     

Methylprednisolone pharmacokinetics, cortisol response, and adverse effects in black and white renal transplant recipients

It is generally assumed that chronic glucocorticoid therapy is similar pharmacologically when administered to either black or white renal transplant recipients, resulting in adrenal suppression, low circulating plasma cortisol concentrations, and a similar degree of drug exposure and toxicity. To examine this theory and to investigate the relationship of glucocorticoid metabolism to steroid-induced adverse effects among specific ethnic groups of renal transplant recipients, 9 black and 9 white male patients chronically receiving methylprednisolone were enrolled. All patients had stable renal function and were matched for age, weight, and time since transplant. Standard pharmacokinetic parameters for methylprednisolone were determined and cortisol responses were characterized by total cortisol area under the concentration curve (AUC), return cortisol AUC, and cortisol suppression half-life. All patients received their daily oral dose of methylprednisolone (mean daily dose = 11 mg for blacks and 11 mg for whites) as an intravenous infusion with serial plasma samples obtained over 24 h. The patients were assessed for the presence of specific cushingoid manifestations (buffalo hump, moon facies) and steroid-associated diabetes. Methylprednisolone and cortisol were analyzed via HPLC. In the black patients, the mean clearance of methylprednisolone (206 +/- 70 ml/hr/kg) was significantly slower with a smaller volume of distribution (0.95 +/- 0.32 L/kg) when compared with the white group (327 +/- 129 ml/hr/kg, P = 0.03; volume of distribution = 1.33 +/- 0.27 L/kg, P = 0.015). Despite chronic methylprednisolone therapy, a definite 24-hr cortisol response pattern was noted in 15 of the 18 patients with a mean total cortisol AUC of 732 +/- 443 ng.hr/ml in blacks and 539 +/- 361 ng.hr/ml in whites (P = 0.17, black vs. white). The mean cortisol suppression half-life was 4.31 +/- 1.54 hr in black recipients and 4.11 +/- 1.49 hr in whites (P = 0.48). The mean return cortisol AUC for the black patients was 327 +/- 279 ng.hr/ml and 370 +/- 207 ng.hr/ml for white patients (P = 0.28). The serum cortisol nadir for black patients was 12.3 +/- 7.2 ng/ml, which was significantly higher than the cortisol nadir in white patients (6.4 +/- 4.4 ng/ml; P = 0.03). A majority (94%) of patients (9 black, 8 white) had moon facies and 27% of patients (3 black, 1 white) had a buffalo hump. While 5 of 9 black patients had steroid-associated diabetes, no white patients manifested this adverse effect. The black patients with diabetes had higher cortisol AUCs with lower methylprednisolone clearances than the white group.(ABSTRACT TRUNCATED AT 400 WORDS)     

Double-blind, comparative study of rufloxacin once daily versus amoxicillin three times a day in treatment of outpatients with exacerbations of chronic bronchitis

In a double-blind, randomized, multicenter study, the efficacy and safety of two dosage schedules of rufloxacin once daily were compared with those of amoxicillin three times a day in the treatment of 192 outpatients with exacerbations of chronic bronchitis. Rufloxacin was given as a single oral dose of 400 mg on day 1 and single daily doses of 200 mg on the subsequent 9 days (n = 64) or as 300 mg on day 1 and then 150 mg daily for 9 days (n = 63); amoxicillin was given as 500 mg orally three times a day for 10 days (n = 65). Clinical and bacteriological assessments were carried out before treatment, between study days 3 and 5, and at days 1 and 8 after treatment. Pretreatment cultures were positive for 139 patients, the most frequently isolated pathogens being Streptococcus pneumoniae, Moraxella catarrhalis, and Haemophilus influenzae. Clinical success rates were comparable in the three groups (94, 95, and 98%, respectively), as were bacteriological success rates at the end of treatment (93, 95, and 91%, respectively) and at follow-up (88, 95, and 98%, respectively). The power to detect a significant 15% difference in cure rates was 74.9%. Follow-up bacteriological failures from pneumococcal infection were 18% in both rufloxacin groups combined and 5% in the amoxicillin group. The 200-mg dose regimen achieved average steady-state concentrations in plasma higher than did the 150-mg dose regimen (3.75 versus 2.72 micrograms/ml). Adverse events occurred in 11 and 13 patients, respectively, on rufloxacin and 8 on amoxicillin. This study shows that rufloxacin once daily ay be a possible option for the treatment of acute exacerbations of chronic bronchitis. The 200-mg daily oral dose preceeded by a loading dose of 400 mg displays a better pharmacokinetic profile than the lower dose.     

Long term effects of 50 mg acetylsalicylic acid alone and in combination with dipyridamole on platelet function after coronary bypass surgery

In a prospective randomized trial in 42 patients undergoing coronary artery bypass surgery, we analyzed the long term platelet inhibiting effects of 50 mg acetylsalicylic acid (ASA) by itself and in combination with dipyridamole (2 x 200 mg), in comparison with phenprocoumon. Three and six months therapy led to significant inhibition of maximum aggregation induced by collagen 1 microgram/ml in platelet rich plasma (PRP) by more than 50% (p < or = 0.05). In PRP stimulated with 5 micrograms/ml collagen maximum inhibition amounted to nearly 20% (n.s.). The groups treated with ASA/ASA + dipyridamole showed an ADP threshold concentration 2.5 times higher than the group treated with phenprocoumon (p < or = 0.05). After stimulation with collagen 1 microgram/ml and 5 micrograms/ml thromboxane B2 synthesis in vitro in both groups treated with ASA was reduced to 1% of the base line values (p < or = 0.01). Inhibition of aggregation in whole blood appeared evident, but was not statistically significant due to considerable fluctuation of measurement. An additional effect of dipyridamole was not detectable. In conclusion, treatment with 50 mg ADA/d results in a lasting, effective inhibition of aggregation of platelets in patients with coronary artery bypass surgery. There is no synergistic effect of additional dose of 400 mg dipyridamole/d.     

An open, randomized study of ketoprofen in patients in surgery for Achilles or patellar tendinopathy

OBJECTIVE: To assess the concentration of ketoprofen, after topical plaster application, in various tissues in relation to plasma levels in 60 patients undergoing surgery for Achilles or patellar tendinopathy; and to analyze whether tissues act as a reservoir of ketoprofen, by evaluating tissue concentrations in relation to plasma concentration at various time points after removal of the plaster. No attempt was made to study the clinical effect of treatment per se. METHODS: In random order to patients applied 30 mg plasters once daily for 5 consecutive days (n = 30), or took a single oral dose 50 mg (n = 30) before surgery. Tissue samples of skin, subcutaneous fat, tendon sheath, and tendon, and plasma were collected intraoperatively at 0, 6 and 14 hours after removal of the 5th plaster, and at 2, 6, and 14 hours after oral intake. Ketoprofen concentration was determined by a validated GC/MS method. The low limit of quantification was 0.5 ng/ml plasma and 0.5 ng/50 mg tissues. RESULTS: High concentrations of ketoprofen were observed in fat, tendon sheath, and tendon after topical applications, whereas plasma levels of ketoprofen were low. CONCLUSION: Ketoprofen attains high concentrations in subcutaneous tissues after multiple topical applications. Subcutaneous tissues appear to act as a reservoir of ketoprofen.     

Dextromethorphan phenotyping and haloperidol disposition in schizophrenic patients

This study examined the relationship between the metabolic ratios of dextromethorphan/dextrorphan, haloperidol disposition, and the incidence of extrapyramidal side effects in schizophrenic patients. Eighteen schizophrenic patients were phenotyped with a test dose of dextromethorphan prior to the initiation of haloperidol treatment. The metabolic ratio of dextromethorphan/dextrorphan was determined in each patient. Patients were treated with oral haloperidol 10 mg/day for 2 weeks. Blood samples for haloperidol and reduced haloperidol were obtained at week 2 of haloperidol treatment. Haloperidol and reduced haloperidol plasma concentrations were assayed by HPLC with electrochemical detection. Significant correlations of dextromethorphan/dextrorphan metabolic ratios vs. plasma haloperidol concentrations, reduced haloperidol concentrations, and reduced haloperidol/haloperidol ratios were found (r = 0.726, P = 0.0007; r = 0.782, P = 0.0001; and r = 0.619, P = 0.006, respectively). Ten patients who experienced extrapyramidal side effects had higher reduced haloperidol concentrations and reduced haloperidol/haloperidol ratios than the other patients (2.49 +/- 1.42 [S.D.] ng/ml vs. 1.10 +/- 0.46 ng/ml, P = 0.014 and 0.287 +/- 0.102 vs. 0.192 +/- 0.065, P = 0.030). The former also had a trend to have higher haloperidol concentrations and dextromethorphan/dextrorphan ratios than the latter (8.04 +/- 2.91 ng/ml vs. 5.83 +/- 1.79 ng/ml, P = 0.066 and 0.023 +/- 0.017 vs. 0.011 +/- 0.010, P = 0.077). Phenotyping patients has the potential to assist clinicians in predicting plasma drug concentrations during the subsequent neuroleptic drug treatment. Further research with phenotyping and psychotropic drug metabolism in psychiatric patients is needed.     

Plasma levels and effect on heart rate and blood pressure of metoprolol after acute oral administration in 12 geriatric patients

Metoprolol, a cardioselective beta-blocking agent, has been given orally to 12 geriatric patients with moderate hypertension. Drug levels of metoprolol as well as the effect of the drug on resting heart rate and BP were studied. Metoprolol was given in a dose of 20 mg, and 8 of the 12 patients also received a 50 mg dose. After the 20 mg dose the peak drug plasma concentration varied between 5 and 80 ng/ml (mean 33), and after the 50 mg dose between 14 and 212 ng/ml (mean 111). This variation is much greater than that seen in earlier studies on healthy volunteers and on a group of non-geriatric hypertensive patients. Plasma half-life of metoprolol averaged about 3.5 hours after both the 20 mg and the 50 mg dose; this does not differe from the plasma half-life in earlier studies in younger age groups. The variability observed in the study might be explained multifactorially, e.g. by different body weight, absorption and/or first-pass effect of the drug.