Pharmacokinetics and safety of a novel influenza treatment (baloxavir marboxil) in Korean subjects compared with Japanese subjects

Baloxavir marboxil, a novel influenza therapeutic agent, is a prodrug rapidly metabolized into its active form, baloxavir acid, which inhibits cap‐dependent endonuclease. This study evaluated the pharmacokinetics (PKs) and safety of baloxavir acid in healthy Korean subjects and compared them with published data in Japanese subjects. This open‐label and single‐ascending dose study was conducted in 30 Korean male subjects, with a single oral dose of baloxavir marboxil (20, 40, or 80 mg) administered to eight subjects each; additionally, 80 mg was administered to six subjects (body weight >80 kg). Noncompartmental and population PK analyses were performed, and results were compared with those of Japanese subjects. Appropriateness of the body weight‐based dosing regimen was evaluated by simulation. PK profiles of baloxavir acid revealed multicompartment behavior with a long half‐life (80.8–98.3 h), demonstrating a dose‐proportional increase. Baloxavir acid reached peak plasma concentration from 3.5 to 4.0 h postdosing. Body weight was identified as a significant covariate of apparent oral clearance and apparent volume of distribution, which was similar to that observed in Japanese subjects. Body weight‐adjusted analysis revealed that exposure to baloxavir acid did not significantly differ between Korean and Japanese subjects. Simulated exposures to baloxavir acid demonstrated that the body weight‐based dosing regimen for baloxavir marboxil was appropriate. Based on a PK study, clinical data including dosing regimen developed in Japan were adequately extrapolated to Korea, supporting the approval of baloxavir marboxil in Korean as a new treatment option for influenza.

Study Highlights

• WHAT IS THE CURRENT KNOWLEDGE ON THE TOPIC?

Baloxavir marboxil, a novel influenza therapeutic agent, has been approved in Japan (first global approval; February 2018) and in the United States (October 2018). The recommended dosage for patients depends on body weight: 40 mg (40–80 kg), 80 mg (≥80 kg). However, no clinical data was available for adequate clinical use in the Korean population.

• WHAT QUESTION DID THIS STUDY ADDRESS?

What are the pharmacokinetic characteristics of baloxavir acid in Koreans, and will it show similar characteristics to those in Japanese?

• WHAT DOES THIS STUDY ADD TO OUR KNOWLEDGE?

Pharmacokinetics of baloxavir acid were similar to those of Japanese population. Simulated exposures to baloxavir acid demonstrated that the body weight‐based dosing regimen for baloxavir marboxil was appropriate in Korean population. This study provided the pharmacokinetic data to support the approval of baloxavir marboxil in Korea (November 2019) as a new treatment option for influenza.

• HOW MIGHT THIS CHANGE CLINICAL PHARMACOLOGY OR TRANSLATIONAL SCIENCE?

Based on this pharmacokinetic study, the efficacy, safety, and body weight‐based dosing regimen data developed in foreign countries could be adequately extrapolated to Korea.     

Cost-effectiveness of baloxavir marboxil compared to laninamivir for the treatment of influenza in Japan

BackgroundBaloxavir marboxil (baloxavir) is a new oral antiviral for influenza types A and B.ObjectivesTo determine the cost-effectiveness of baloxavir versus laninamivir in otherwise healthy (OwH) adults in Japan.MethodsA decision tree was utilized to describe the course of influenza and predict associated costs and quality-adjusted life-years (QALYs) over one year by antiviral. Costs were valued from the public healthcare payer perspective, including influenza test, antiviral acquisition, other medications, physician visits, other outpatient costs associated with influenza or drug-related adverse events (DRAEs), and hospitalizations. Resource utilization and unit costs were obtained from the analysis of the JammNet claims database. Health state utilities were obtained from a clinical trial of baloxavir and previous models, and were driven by influenza symptoms, DRAEs, and complications caused by influenza. Sensitivity analyses were also performed.ResultsThe total payer expenditure per patient for baloxavir versus laninamivir was ¥9383 versus ¥9132. The additional acquisition costs of baloxavir were partly offset by the DRAE costs avoided. Baloxavir showed a small gain in QALYs versus laninamivir and the incremental cost per QALY gained (¥2,231,260) was lower than the considered willingness-to-pay threshold (¥5,000,000/QALY). Key model drivers were the probability of DRAEs and the duration of symptoms. The probability of baloxavir being cost-effective was 64%.ConclusionThis cost-effectiveness study on baloxavir suggests that it would be cost-effective compared to laninamivir in OwH adults in Japan. Further studies are needed in different settings such as high-risk population and with different comparators.     

Acute ischemic colitis with hematochezia related to baloxavir marboxil treatment for influenza A

Oseltamivir, an established oral anti-influenza medication, increases the risk of ischemic colitis. Baloxavir marboxil is a novel oral anti-influenza medication, and few studies have evaluated its potential side effects, including ischemic colitis. Moreover, as influenza A can also induce ischemic colitis, drug-induced colitis associated with anti-influenza medication is not clearly understood. In this report, we describe the case of a 62-year-old Japanese woman who developed acute ischemic colitis after taking baloxavir for influenza A. The day after taking baloxavir (day 2), the patient experienced abdominal pain, diarrhea, and nausea. On day 3, she had developed hematochezia and decided to visit our hospital. Upon presentation, inflammation of the descending and sigmoid colon was detected by abdominal echography and computed tomography. Fluid replacement therapy and dietary restrictions were initiated. On day 4, the inflammation of the descending colon and marked intestinal edema were confirmed by colonoscopy. She was clinically diagnosed with ischemic colitis, from which she recovered completely by day 9. This case suggests that patients taking baloxavir may be at risk of developing ischemic colitis with hematochezia and underscores the need to further study the induction of this condition by commonly used oral anti-influenza agents.     

美国食品药品监督管理局批准新药Xofluza(baloxavir marboxil)用于流感治疗

2018年10月24日(罗氏新闻)——罗氏公司今日宣布,美国食品药品监督管理局已批准Xofluza(baloxavir marboxil)用于12岁及12岁以上急性、无并发症流感患者的治疗。Xofluza是首个、单剂量口服药物,通过抑制流感病毒复制所必需的酸性核酸内切酶的聚合酶而发挥作用。在非临床研究中,Xofluza对多种流感病毒有效,包括奥司他韦耐药株和禽流感病毒(H7N9、H5N1)。     

Safety and effectiveness of baloxavir marboxil for the treatment of influenza in Japanese clinical practice: A postmarketing surveillance of more than 3000 patients

Baloxavir marboxil is an oral anti-influenza drug that inhibits the cap-dependent endonuclease of the virus polymerase acidic protein. In clinical trials, baloxavir reduced the time to alleviation of influenza symptoms and time to resolution of fever in adults, adolescents, and children. The purpose of this study is to collect data on the safety and effectiveness of baloxavir when used in clinical practice. This postmarketing surveillance (clinicaltrials.jp; JapicCTI-183882), conducted at 688 Japanese hospitals or clinics (March 2018 to March 2019), enrolled patients of any age with influenza A or B infection who received a single, weight-based dose of baloxavir. Adverse drug reactions (ADRs) were seen in 11.2% of 3094 patients during the 7-day observation period; the most common ADR was diarrhea (6.1%). ADRs were more common in children aged <12 years (14.1%) than in adults (10.0%). Almost all ADRs were non-serious (98.9%) and were recovered or recovering (96.7%). Median time to alleviation of symptoms (N = 2884) was 2.5 days (overall, influenza A, and influenza B groups). Median time to resolution of fever (N = 2946) was 1.5 days (overall, influenza A, and influenza B groups). Biphasic fever (increased temperature after previous fever resolution) was seen in 6.7% of patients overall and 28.6% of patients <6 years infected with influenza B, similar to rates published elsewhere with other influenza drugs and in untreated influenza. This postmarketing surveillance of >3000 patients suggests that baloxavir is well tolerated and effective regardless of patient age or influenza virus type.     

Open-label study of the safety,pharmacokinetics, and effectiveness of a 2 mg/kg dose of baloxavir marboxil 2% granules in children <20 kg with influenza

IntroductionBaloxavir marboxil is an oral anti-influenza drug with demonstrated safety and efficacy in pediatric patients when a 2% granules formulation is administered at 1 mg/kg. This study assessed safety, effectiveness, and pharmacokinetics of a higher dose (2 mg/kg) of baloxavir marboxil 2% granules in pediatric patients weighing <20 kg.MethodsThis multicenter, open-label, noncontrolled study was conducted at 15 sites in Japan (January 2019–March 2020; JapicCTI-194577). Patients aged <12 years with confirmed influenza received a single oral dose of baloxavir marboxil at 2 mg/kg if body weight was <10 kg or 20 mg if ≥ 10 to <20 kg. Safety, pharmacokinetics, effectiveness (time to illness alleviation [TTIA] of influenza; time to resolution of fever; virus titer), and polymerase acidic protein (PA) substituted viruses were assessed over 22 days.Results45 patients, all aged ≤6 years, were enrolled. Adverse events were reported in 24 (53.3%) patients, most commonly nasopharyngitis, diarrhea, and upper respiratory tract infection. Median (95% confidence interval [CI]) TTIA was 37.8 (27.5–46.7) hours; median (95% CI) time to resolution of fever was 22.0 (20.2–28.6) hours. A >4 log decrease in mean viral titer occurred at day 2 and a subsequent temporary 1–2 log increase in patients with influenza A(H3N2) and B. Treatment-emergent PA/I38X-substituted virus was detected in 16/39 (41.0%) patients, but no prolonged TTIA or time to resolution of fever was associated with its presence.ConclusionsBaloxavir granules administered at 2 mg/kg in children <20 kg were well tolerated, with symptom alleviation similar to 1 mg/kg.     

Pharmacokinetics,safety, and efficacy of bosentan in pediatric patients with pulmonary arterial hypertension

BACKGROUND: Bosentan, a dual endothelin-receptor antagonist, is registered for the treatment of pulmonary arterial hypertension. Little is known about the effects of bosentan in children. This study was conducted to investigate the pharmacokinetics, safety, and efficacy of bosentan in pediatric patients with pulmonary arterial hypertension. METHODS: In this 2-center, open-label study, 19 pediatric patients with pulmonary arterial hypertension were enrolled and stratified for body weight and epoprostenol use. Patients weighing between 10 and 20 kg, between 20 and 40 kg, or greater than 40 kg received a single dose of 31.25, 62.5, or 125 mg, respectively, on day 1, followed by 4 weeks of treatment with the initial dose. The dose was then up-titrated to the target dose (31.25, 62.5, or 125 mg twice daily). Pharmacokinetic and hemodynamic parameters were obtained at baseline and after 12 weeks of treatment. Six-minute walk distance and cardiopulmonary exercise testing results were measured at baseline and at week 12 in children aged 8 years or older. RESULTS: The variability in exposure among the 3 groups was less than 2-fold after single- and multiple-dose administration. The exposure to bosentan decreased over time in all groups. The covariates body weight, gender, age, and the use of epoprostenol had no significant effect on the pharmacokinetics of bosentan. Bosentan produced hemodynamic improvement and was well tolerated. The mean change from baseline in mean pulmonary artery pressure was -8.0 mm Hg (95% confidence interval, -12.2 to -3.7 mm Hg), and that in pulmonary vascular resistance index was -300 dyne x s x m(2)/cm(5) (95% confidence interval, -576 to -24 dyne x s x m(2)/cm(5)). CONCLUSIONS: The pharmacokinetics of bosentan in pediatric patients with pulmonary arterial hypertension and healthy adults are similar, and treatment with bosentan resulted in hemodynamic improvement. These results suggest that the applied dosing regimens may be appropriate to treat pediatric patients.     

Pharmacokinetics, in-vitro activity, therapeutic efficacy and clinical safety of aztreonam vs. cefotaxime in the treatment of complicated urinary tract infections

The minimal inhibitory concentrations (MICs) of aztreonam and cefotaxime were determined against 400 isolates from urological in-patients with complicated and/or hospital acquired urinary tract infections (UTI). Against the Gram-negative rods the activities of both antibiotics were comparable except for higher activity of aztreonam against Pseudomonas aeruginosa. The pharmacokinetic study in nine elderly patients showed a prolonged plasma half life of aztreonam (2.7 h) as compared to younger volunteers (1.6-1.9 h). In a prospective randomized study 39 urological patients with complicated and/or hospital acquired UTI were treated with 1 g aztreonam or cefotaxime iv twice daily for 4 to 15 days. Cure was obtained in 5 out of 18 patients in the aztreonam and 7 out of 20 patients in the cefotaxime group. There were 3 superinfections, 7 relapses and 3 reinfections in the aztreonam group and 1 failure, 1 superinfection, 6 relapses and 5 reinfections in the cefotaxime group. There was no significant difference in therapeutic efficacy between the two antibiotics. Both antibiotics were tolerated well and seem to be equally effective in the treatment of complicated UTI caused by sensitive organisms.     

帕拉米韦治疗儿童甲流的疗效及安全性

目的评价帕拉米韦治疗儿童甲型流感的临床疗效及安全性。方法将2016年6月至2017年1月北京儿童医院收治的确诊甲型流感患儿,采用帕拉米韦氯化钠注射液治疗。观察治疗后症状缓解时间、发热缓解时间及不良反应。结果共有150例患儿纳入研究,其中男性79例(52.7%),女性71例(47.3%),平均年龄(3.9±3.0)岁。中位症状缓解时间(95%CI)是27.9 h(20.6~30.8 h),中位发热缓解时间(95%CI)是17.8 h(16.1~19.5 h)。不同年龄组间中位症状缓解时间和中位发热缓解时间的差异无统计学意义(P>0.05)。133例患儿(88.7%)治疗持续时间为1 d,17例患儿(11.3%)治疗持续时间为2 d,没有治疗持续时间3 d或以上患儿。没有并发症发生。不良反应发生率4.0%,全部是胃肠道反应,不良反应多发生在年龄小的儿童,不良反应均出现在治疗开始后的3 d之内,未经干预迅速缓解消退,不良反应发生率没有随剂量次数的增加而增加。结论帕拉米韦治疗儿童甲型流感病毒感染有效,安全性及耐受性良好,与国内外文献报道的疗效和安全性一致。     

Pharmacokinetics and safety of oral levofloxacin in human immunodeficiency virus-infected individuals receiving concomitant zidovudine.

This phase I, double-blind, randomized, placebo-controlled, parallel-design study was conducted to evaluate the safety and pharmacokinetics of levofloxacin in human immunodeficiency virus (HIV)-infected subjects concomitantly receiving a stable regimen of zidovudine (AZT). Sixteen HIV-infected males with CD4-cell counts ranging from 100 to 550 and not experiencing significant AZT intolerance were enrolled. Subjects received levofloxacin (350 mg of levofloxacin hemihydrate) or a placebo (eight subjects per treatment group) as a single oral dose on day 1, multiple doses every 8 h from days 3 to 9, and a single dose on day 10. On days 1 and 10, an AZT dose (100 mg) was administered concurrently with the study drug. In between these doses, AZT was administered according to the regimen used by the subject prior to entering the study up to a maximum of 500 mg/day. Plasma levofloxacin concentrations were monitored for 36 h after levofloxacin dosing on day 1, immediately prior to the morning doses on days 3 to 9, and for 72 h after dosing on day 10. Plasma AZT concentrations were monitored on day 0 for baseline (for 6 h after the AZT dose) and for 4 h after the AZT doses on days 1 and 10. Levofloxacin was rapidly absorbed (time to maximum plasma concentration, approximately 1.0 h) and extensively distributed in the body with an apparent volume of distribution of approximately 104 liters (approximately 1.34 liters/kg). Steady-state conditions on day 10 were confirmed. Pharmacokinetic profiles of levofloxacin from single doses and multiple (three-times-daily) doses were similar, with a moderate accumulation (observed day 10-to-day 1 ratio of the maximum plasma concentration, approximately 185% versus expected 169%; for the corresponding ratio of the area under the concentration-time curve from 0 to 8 h [AUC(0-8)], the values were observed 217% versus expected 169%) at steady state. Mean average steady-state peak plasma concentration, plasma levofloxacin concentration at the end of the dosing interval, AUC(0-8), terminal half-life, and total body clearance were 7.06 microg/ml, 3.62 microg/ml, 37.4 microg x h/ml, 7.2 h, and 9.4 liters/h (0.12 liters/h/kg), respectively. Pharmacokinetic profiles of levofloxacin in HIV-infected patients did not appear to be affected by the concomitant administration of AZT; nor were AZT pharmacokinetics altered by levofloxacin. Oral administration of 350 mg of levofloxacin hemihydrate every 8 h appeared to be well tolerated by the subjects. There were no apparent differences in adverse events between the two treatment groups. There were no clinically significant changes from baseline in any laboratory parameter or vital sign following treatments observed in this study. The study results suggest that there is no need for levofloxacin dosage adjustment in HIV-seropositive subjects who concomitantly receive AZT.     

Pharmacokinetics, safety, and efficacy of posaconazole in patients with persistent febrile neutropenia or refractory invasive fungal infection

The pharmacokinetic profiles, safety, and efficacies of different dosing schedules of posaconazole oral suspension in patients with possible, probable, and proven refractory invasive fungal infection (rIFI) or febrile neutropenia (FN) were evaluated in a multicenter, open-label, parallel-group study. Sixty-six patients with FN and 32 patients with rIFI were randomly assigned to one of three posaconazole regimens: 200 mg four times a day (q.i.d.) for nine doses, followed by 400 mg twice a day (b.i.d.); 400 mg q.i.d. for nine doses, followed by 600 mg b.i.d.; or 800 mg b.i.d. for five doses, followed by 800 mg once a day (q.d.). Therapy was continued for up to 6 months in patients with rIFI or until neutrophil recovery occurred in patients with FN. The 400-mg-b.i.d. dose provided the highest overall mean exposure, with 135% (P = 0.0004) and 182% (P < 0.0001) greater exposure than the 600-mg-b.i.d. and 800-mg-q.d. doses, respectively. However, exposure in allogeneic bone marrow transplant (BMT) recipients (n = 12) was 52% lower than in non-BMT patients. Treatment-related adverse events (occurring in 24% of patients) were mostly gastrointestinal in nature. Twenty-four percent of patients had adverse events leading to premature discontinuation (none were treatment related). In efficacy-evaluable patients, successful clinical response was observed in 43% with rIFI (56% of patients receiving 400 mg b.i.d., 17% receiving 600 mg b.i.d., and 50% receiving 800 mg q.d.) and 77% with FN (74% receiving 400 mg b.i.d., 78% receiving 600 mg b.i.d., and 81% receiving 800 mg q.d.). Posaconazole is well tolerated and absorbed. Divided doses of 800 mg (400 mg b.i.d.) provide the greatest posaconazole exposure.     

Pharmacokinetics,safety, and tolerability of ceftolozane/tazobactam in healthy Japanese,Chinese, and white subjects

Ceftolozane/tazobactam, a novel antibacterial with potent activity against Gram‐negative pathogens, was developed for treatment of complicated urinary tract infections, including pyelonephritis, and intra‐abdominal infections. A phase 1 pharmacokinetic (PK) study of ceftolozane/tazobactam in healthy Japanese, Chinese, and white volunteers was conducted to assess the potential effect of ethnicity on PK. The PK of ceftolozane, tazobactam, and tazobactam metabolite M1 was compared after single 1.5‐ and 3‐g intravenous doses of ceftolozane/tazobactam. Ten Japanese, nine Chinese, and ten white subjects were enrolled, and 27 completed all doses of study medication. Dose‐normalized PK parameters for ceftolozane and tazobactam were similar among Japanese, Chinese, and white subjects (at 1.5‐g and 3‐g doses, ceftolozane area under the plasma concentration–time curve from zero to infinity [AUC_0–∞] = 166.3, 165.9, and 185.5 h μg/mL, respectively, and 157.7, 158.5, and 181.2 h μg/mL, respectively; tazobactam AUC_0–∞ = 48.5, 43.2, and 50.1 h μg/mL, respectively, and 47.3, 43.7, and 50.0 h μg/mL, respectively. The 90% CIs of their ratio estimates were within the range 0.80 to 1.25 with the exception of AUC_0–∞ for ceftolozane after the 3‐g dose (0.79). The cumulative amount of ceftolozane and tazobactam excreted in urine was similar among ethnic groups. For all groups, treatment‐emergent adverse events (AEs) were mild; no deaths or serious AEs were reported. The PK of ceftolozane/tazobactam was approximately dose proportional (i.e. doubling the dose approximately doubles the exposure) and similar among the groups. No dosage adjustment is needed for ceftolozane/tazobactam in Japanese and Chinese patients.     

Randomized study of the efficacy and safety of oral elderberry extract in the treatment of influenza A and B virus infections

Elderberry has been used in folk medicine for centuries to treat influenza, colds and sinusitis, and has been reported to have antiviral activity against influenza and herpes simplex. We investigated the efficacy and safety of oral elderberry syrup for treating influenza A and B infections. Sixty patients (aged 18-54 years) suffering from influenza-like symptoms for 48 h or less were enrolled in this randomized, double-blind, placebo-controlled study during the influenza season of 1999-2000 in Norway. Patients received 15 ml of elderberry or placebo syrup four times a day for 5 days, and recorded their symptoms using a visual analogue scale. Symptoms were relieved on average 4 days earlier and use of rescue medication was significantly less in those receiving elderberry extract compared with placebo. Elderberry extract seems to offer an efficient, safe and cost-effective treatment for influenza. These findings need to be confirmed in a larger study.     

Pharmacokinetics, safety, and tolerability of caspofungin in children and adolescents

Caspofungin is a parenteral antifungal that inhibits beta-1,3-D-glucan synthesis. Although licensed for adult use, the appropriate caspofungin dosing regimen in pediatric patients is not yet known. We therefore investigated the pharmacokinetics and safety of caspofungin in pediatric patients. Thirty-nine children (ages 2 to 11 years) and adolescents (ages 12 to 17 years) with neutropenia were administered caspofungin using either a weight-based regimen (1 mg/kg of body weight/day) or a body surface area regimen (50 mg/m2/day or 70 mg/m2/day). Plasma samples for caspofungin profiles were collected on days 1 and 4. These results were compared to those from adults treated with either 50 or 70 mg/day for mucosal candidiasis. In children receiving 1 mg/kg/day (maximum, 50 mg/day), the area under the concentration-time curve over 24 h (AUC(0-24)) was significantly smaller (46% after multiple doses) than that observed in adults receiving 50 mg/day (P < 0.001). In children and adolescents receiving 50 mg/m2/day (maximum, 70 mg/day), the AUC(0-24) following multiple doses was similar to that for the exposure in adults receiving 50 mg/day. The AUC(0-24) and concentration trough (at 24 h) in pediatric patients receiving the 50-mg/m2 daily regimen were consistent across the range of ages. Caspofungin was generally well tolerated in this study. None of the patients developed a serious drug-related adverse event or were discontinued for toxicity. These results demonstrate that caspofungin at 1 mg/kg/day in pediatric patients is suboptimal. Caspofungin administration at 50 mg/m2/day provides a comparable exposure to that of adult patients treated with 50 mg/day.     

Pharmacokinetics,safety, and tolerability of sulcardine sulfate: an open‐label,single‐dose,randomized study in healthy Chinese subjects

Sulcardine sulfate (Sul) is a novel anti‐arrhythmic agent as a potential treatment for atrial fibrillation and ventricular arrhythmias. This study was conducted to investigate the pharmacokinetic profile, safety, and tolerability of Sul in healthy Chinese subjects. In this open‐label, single‐dose, randomized study, 10 healthy subjects were assigned to receive Sul doses of 200, 400, and 800 mg under fasting conditions (Cohorts A, B, and C, respectively) or 400 mg under fed conditions (Cohort D). The study incorporated a crossover design, separated by a seven‐day washout period. Blood samples were collected before treatment and at successive time intervals up to 48 h after treatment. Sul concentrations in plasma samples were determined using a validated LC‐MS/MS method. Tolerability was determined by clinical evaluation and adverse event (AE) monitoring. Pharmacokinetic results demonstrated that C_max and AUC_(0–t) of Sul increased with an increasing dose. The mean t_1/2 values for Cohorts A, B, and C were 16.85, 17.66, and 11.87 h, respectively. No statistically significant differences were observed between men and women for the main pharmacokinetic parameters, with the exception of t_1/2 in Cohorts B and C. No significant differences were observed in the absorption and bioavailability of Sul between the fed and fasted states (P > 0.05). Four subjects reported mild AEs during the study. No serious AEs were reported. Sul was shown to be safe and well tolerated in healthy Chinese subjects. Pharmacokinetics studies demonstrated that Sul has adequate oral absorption and bioavailability properties.     

多沙唑嗪治疗轻中度高血压疗效和安全性的临床研究

目的 评价新一代α_1受体拮抗剂甲磺酸多沙唑嗪的降压疗效及安全性,并与盐酸特拉唑嗪相比较。方法 采用随机分组平行对照方法,将226例轻、中度高血压患者分成两组:多沙唑嗪组(111例)口服甲磺酸多沙唑嗪2mg/d;盐酸特拉唑嗪组(115例)口服盐酸特拉唑嗪2mg/d。疗程8周。每两周一次上午监测诊室谷值坐位舒张压、心率,立位舒张压,并观察不良反应。用药前及治疗第8周后检测血液生化指标。第2周末谷值坐位舒张压仍大于90mmHg者加量至4mg/d,第4周末谷值坐位舒张压仍大于90mmHg者加量至6mg/d,第6周末谷值坐位舒张压仍大于90mmHg者,终止试验,改服其它药物。结果 治疗8周后甲磺酸多沙唑嗪组与盐酸特拉唑嗪组治疗有效反应率分别为74.77％和76.52％,(P>0.05);治疗后两组平均谷值坐位舒张压均有明显降低(P<0.05)。两组均无严重不良反应发生。结论 甲磺酸多沙唑嗪与盐酸特拉唑嗪降压疗效相似,不良反应发生率均较低,是一种安全、有效的治疗轻、中度原发性高血压的药物。