Low-doses of indinavir boosted with ritonavir in HIV-infected Thai patients: pharmacokinetics, efficacy and tolerability

OBJECTIVES: To assess the steady-state pharmacokinetics of two reduced doses of indinavir boosted with ritonavir (indinavir/ritonavir) in HIV-infected Thai patients. PATIENTS AND METHODS: Thirteen immunocompromised antiretroviral-naive patients (6 males, 7 females) initiated 600/100 mg indinavir/ritonavir, zidovudine and lamivudine, every 12 h. After 1 month, blood samples were taken at pre-dose, and 0.5, 1, 1.5, 2, 2.5, 3, 4, 5, 6, 8 and 12 h after drug intake. Indinavir dosing was then reduced to 400 mg (twice daily) and 1 week later an identical series of samples were drawn. Patients then resumed 600 mg of indinavir. HIV-1 RNA viral load was determined at 8, 24 and 48 weeks. Indinavir plasma levels were determined by HPLC and pharmacokinetic parameters by non-compartmental analysis. RESULTS: Median (range) weight was 58 kg (51-73) for men and 53 kg (46-59) for women. On 600 mg of indinavir, median indinavir AUC, C(max), and C(min) were 39.3 mg.h/L (20.6-50.5), 6.2 mg/L (3.7-9.0) and 0.41 mg/L (0.12-0.77), respectively, and on indinavir 400 mg, 18.3 mg.h/L (11.1-33.0), 3.8 mg/L (2.2-7.8) and 0.17 mg/L (0.10-0.39), respectively. No renal complications were observed. At 48 weeks, 6/13 (46%) patients had stopped 600 mg of indinavir due to intolerability (gastrointestinal and cutaneous), and 5/7 (71%) patients had a HIV-1 viral load <50 copies/mL. CONCLUSIONS: Reduced doses of indinavir/ritonavir maintained adequate indinavir plasma levels compared to current guidelines suggesting that these doses are efficacious in this setting. Considering the poor tolerability of 600 mg of indinavir, the 400 mg of indinavir may be preferred due to its lower exposure indices but long-term efficacy data are needed.     

Comparative study of barnidipine and felodipine in Chinese patients with essential hypertension

This study evaluated the efficacy and safety of barnidipine for the treatment of mild-to-moderate essential hypertension in Chinese patients. A total of 131 patients were randomized to receive either barnidipine (10 -15 mg) or felodipine (5 - 10 mg) once daily for 4 weeks. Both drugs reduced blood pressure significantly, with > or = 87% of patients obtaining a marked or moderate effect. The mean +/- SD reductions in systolic and diastolic blood pressure were 19.2 +/- 13.6 and 14.4 +/- 7.0 mmHg, respectively, for barnidipine treatment, and 20.3 +/- 11.3 and 14.7 +/- 7.7 mmHg, respectively, for felodipine treatment. There were no significant differences between the two drugs in terms of anti-hypertensive effect, heart rate, laboratory test results or incidence of adverse events. More patients taking felodipine experienced palpitations, but this difference was not statistically significant. Barnidipine is as efficacious and safe as felodipine in the treatment of essential hypertension in Chinese patients.     

The long-term efficacy and safety profile of barnidipine

Two multicentre trials have investigated the efficacy and tolerability of treatment with once-daily barnidipine, in patients with mild to moderate essential hypertension. The long-term efficacy and safety of barnidipine were demonstrated in a long-term, multicentre, open-label study. In total, 106, 79 and 32 patients were followed for the first, second and third year, respectively. Patients received barnidipine at a dose titrated to achieve a sitting DBP > or = 90 mmHg or a decrease in sitting BDP > or = 10 mmHg. If necessary, another antihypertensive agent was added to achieve normalisation of blood pressure. In the first year, normalisation of blood pressure was achieved in 91% of patients. This was maintained in 91% and 81% of patients in the second and third years, respectively. At the end of treatment in both years, over 60% of patients remained on barnidipine monotherapy (10 or 20 mg/day). A low incidence of adverse events possibly or probably related to barnidipine (10 or 20 mg/day) monotherapy was reported in the first and second years with headache, peripheral oedema and palpitations the most commonly reported. In the third year of follow-up, only one adverse event, an ECG abnormality, was considered to be possibly related to the study medication. The effective 24 hour control of blood pressure with barnidipine monotherapy was confirmed in a randomised, double-blind, placebo-controlled, cross-over study of 20 patients. These patients were given 6 week regimens of both barnidipine (20 mg/day) and placebo. Office and 24 hour ambulatory blood pressures were recorded at the end of each treatment phase. Barnidipine lowered blood pressure to a significantly greater extent than placebo both at night and during the day. Adverse events were classified as mild or moderate and fewer adverse events were reported with barnidipine treatment compared with placebo. Barnidipine monotherapy (20 mg/day) is safe and effective in providing 24 hour control of blood pressure. Furthermore, the efficacy and tolerability of barnidipine monotherapy (10 or 20 mg/day) are maintained for at least 2 years.     

Comparison of the efficacy and tolerability of lisinopril and sustained-release verapamil in black patients with hypertension.

In this clinical study the efficacy and tolerability of lisinopril and sustained-release (SR) verapamil hydrochloride were compared in black patients with mild-to-moderate uncomplicated essential hypertension. The goal of therapy was to achieve a supine diastolic blood pressure (SDBP) of less than 90 mmHg or a greater than or equal to 10-mmHg fall in SDBP. Forty-three patients completed the titration phase, 23 in the lisinopril group and 20 in the verapamil SR group. The mean baseline supine systolic/diastolic blood pressures were 147/98 mmHg for the lisinopril group and 155/100 mmHg for the verapamil SR group. At the end of a two- to eight-week titration period, 87% of the lisinopril-treated patients and 90% of the verapamil SR-treated patients had achieved SDBP control. Six patients were excluded from maintenance therapy: four in the lisinopril group (one because of urticaria and three because of failure to reach goal blood pressure) and two in the verapamil SR group (because of failure to reach goal blood pressure). After eight weeks of maintenance therapy, 68% of the lisinopril-treated patients and 72% of the verapamil SR-treated patients had achieved SDBP control. The mean decreases in SDBP were comparable for both treatment groups. At the end of titration, the mean decreases from baseline were 10.5 mmHg for the lisinopril group and 12.6 mmHg for the verapamil SR group. At the end of maintenance, the mean decreases from baseline were 7.8 mmHg for the lisinopril group and 9.2 mmHg for the verapamil SR group. Adverse experiences were few.(ABSTRACT TRUNCATED AT 250 WORDS)     

Comparison of the efficacy and tolerability of lisinopril and sustained-release verapamil in older patients with hypertension.

The efficacy and tolerability of lisinopril and sustained release (SR) verapamil hydrochloride were compared in 68 patients (mean age, 60 years) with mild to moderate uncomplicated essential hypertension. The goal of therapy was to achieve and maintain a supine diastolic blood pressure (SDBP) of less than 90 mmHg or a fall in SDBP greater than or equal to 10 mmHg. Patients received lisinopril (10 to 40 mg QD) or verapamil SR (120 to 480 mg QD) during a variable titration period (two to eight weeks) to achieve goal blood pressure prior to a four-week maintenance treatment period. Among the 62 patients who completed the titration period, the mean baseline supine systolic/diastolic blood pressures were 155/97 mmHg for the lisinopril group and 150/95 mmHg for the verapamil SR group. Ninety-seven percent of patients in the lisinopril group and 100% of patients in the verapamil SR group achieved SDBP control at the end of titration therapy. At the end of the maintenance treatment period, 82% of the lisinopril-treated patients and 81% of the verapamil SR-treated patients had SDBP control. Mean decreases in SDBP from baseline were comparable for both treatment groups. At the end of titration, mean decreases were 11.3 mmHg for the lisinopril group and 10.7 mmHg for the verapamil SR group; at the end of maintenance treatment, mean decreases were 10.5 mmHg and 8.5 mmHg. Thus both drugs were equally effective in older patients with mild to moderate essential hypertension. Both drugs were generally well tolerated. One patient in the lisinopril group and four patients in the verapamil SR group experienced adverse effects that required withdrawal from the study.     

Efficacy and safety of barnidipine compared with felodipine in the treatment of hypertension in Chinese patients

The efficacy and safety profiles of barnidipine in the treatment of hypertension were evaluated in an open parallel-group study. Fifty-nine Chinese patients with mild-to-moderate essential hypertension were randomized to receive either barnidipine or felodipine (5 mg once daily, titrated to 10 mg or 15 mg once daily, as indicated) for 12 weeks. Both drugs reduced blood pressures significantly with > or = 68% of cases obtaining marked or moderate blood pressure reduction. Mean reductions in systolic and diastolic blood pressure for barnidipine treatment were 23.7 +/- 13.5 mmHg and 12.7 +/- 7.9 mmHg, and for felodipine, 24.3 +/- 18.4 mmHg and 14.5 +/- 10.0 mmHg, respectively. There was no significant difference between these two drugs in anti-hypertensive effect, heart rate, laboratory measurements or incidence of adverse events. The only difference was that more patients taking felodipine experienced palpitations. We conclude that barnidipine has similar efficacy and a similar safety profile to felodipine in the treatment of mild-to-moderate essential hypertension in Chinese patients.     

Efficacy and tolerability of cycletanine in aged patients with hypertension

Moderate arterial hypertension of the elderly has to be treated but the efficacy has to be progressive. Cicletanine has a pharmacokinetic profile well fitted to the therapy of this age group. The mechanism of action is characterized by synthesis of prostacyclin. A double blind prospective randomized study was conducted at two institutions on 132 patients aged more than 60, with diastolic arterial pressure over 95 mmHg and systolic over 160 mmHg. 62.9% of them were aged more than 75. The analysis of those two studies shows that the three groups with cicletanine (respectively 50, 100 and 150 mg per day) had a significant decrease of both pressures versus placebo. In the 50 mg group, 40% of arterial pressures were normalized after 3 months of treatment. There were no difference between 50 and 100 mg. There were no adverse drug reaction like falling down, day or night, or orthostatic hypotension. The biological tolerance, more particularly renal, was excellent with this dose of 50 mg a day. Cicletanine at the dose of 50 mg/day is a recommended treatment in arterial hypertension of the elderly.     

Increased efficacy and tolerability with losartan plus hydrochlorothiazide in patients with uncontrolled hypertension and therapy-related symptoms receiving two monotherapies

The efficacy and tolerability of losartan 100 mg/hydrochlorothiazide (HCTZ) 25 mg and enalapril 10 mg/HCTZ 25 mg were compared in a double-blind, randomized trial in hypertensive patients inadequately controlled and experiencing side effects on prior therapy. Patients with moderate or severe hypertension, currently treated with at least two single-agent drugs (excluding angiotensin-converting enzyme inhibitors), with a sitting diastolic blood pressure (DBP) above 90 mm Hg, and at least one undesirable drug-related symptom were randomized to once-daily treatment with one of the combinations for 12 weeks. Losartan/HCTZ lowered sitting DBP from the prior therapy baseline by 13.7 mm Hg and sitting systolic blood pressure 19.3 mm Hg; similar reductions occurred with enalapril/HCTZ. Trough sitting DBP was reduced to normal levels (< 90 mm Hg) in 63% of patients switched to the losartan combination and in 58% of those treated with the enalapril combination. Each combination was associated with improved tolerability compared with prior therapy, although fewer patients reported each of 24 undesirable symptoms after 12 weeks of losartan/HCTZ. The improvement from prior therapy in the occurrence of cough was significantly greater with losartan/HCTZ (P = .005). Enalapril/HCTZ, but not losartan/HCTZ, increased serum uric acid levels at week 12. In conclusion, the combination of losartan 100 mg/HCTZ 25 mg offers a beneficial therapeutic option for patients with a history of moderate to severe hypertension whose blood pressure is not adequately controlled or who exhibit side effects while on two or more single-agent antihypertensive drugs. In this population, the switch from prior antihypertensive therapies to once daily losartan 100 mg/HCTZ 25 mg improves blood pressure control and reduces side effects.     

盐酸贝尼地平治疗高血压疗效观察

目的 观察盐酸贝尼地平的临床降压疗效、安全性及不良反应方法随机选择58例老年高血压患者,采用盐酸贝尼地平口服治疗,6～8周为一疗程,观察降压疗效、安全性及副作用,并对58例入选者进行治疗前后动态血压监测时照.结果 58例口服盐酸贝尼地平的病人,显效36例,有效12例,总有效率82.8%.结论 口服盐酸贝尼地平降压效果明显,安全可靠.     

Effect of barnidipine on blood pressure and serum metabolic parameters in patients with essential hypertension: a pilot study

The effect of barnidipine, a calcium channel blocker, on metabolic parameters is not well known. The authors conducted the present pilot study to evaluate the possible effects of barnidipine on parameters involved in atherogenesis, oxidative stress, and clotting activity. This open-label intervention study included 40 adult patients with essential hypertension who received barnidipine 10 mg once daily. Barnidipine significantly reduced systolic and diastolic blood pressure as well as isoprostane levels, which represent a reliable marker of oxidative stress. In contrast, barnidipine had a neutral effect on lipid profile and apolipoprotein levels, did not influence glucose homeostasis, had no effect on renal function, and did not cause any changes in electrolyte levels. Moreover, barnidipine did not affect either the clotting/fibrinolytic status (evaluated by measurement of fibrinogen, total plasminogen activator inhibitor, tissue plasminogen activator, and a2 antiplasmin) or the enzymatic activity of the inflammatory/anti-inflammatory mediators lipoprotein-associated phospholipase A2 and paraoxonase 1, respectively. Barnidipine should be mainly considered as an antihypertensive agent with neutral effects on most of the studied metabolic parameters in hypertensive patients. Any antioxidant effect of barnidipine needs further investigation.     

The efficacy of telmisartan compared with perindopril in patients with mild-to-moderate hypertension

In this study, efficacy of the angiotensin II type 1 receptor blocker telmisartan given as monotherapy was compared with that of perindopril monotherapy in patients with mild-to-moderate hypertension. After a 2-week, single-blind, placebo run-in period, 60 patients were randomised to double-blind, once-daily treatment with telmisartan 80 mg or perindopril 4 mg for 6 weeks. Clinic and ambulatory blood pressure measurements and clinical laboratory evaluation were performed at the end of the placebo run-in and active treatment phases. Both telmisartan and perindopril significantly (p < 0.0001) reduced clinic systolic blood pressure (SBP) and diastolic blood pressure (DBP) compared with baseline values. Also, both drugs significantly (p < 0.0001) reduced 24-h mean ambulatory SBP and DBP compared with baseline. Comparison of the mean hourly antihypertensive activities showed that the reduction in mean ambulatory DBP for the last 8 h of the dosing interval was significantly greater (p < 0.05) in telmisartan-treated patients. A 24-h mean DBP of <85 mmHg was observed in 66.6% of the telmisartan-treated patients but in only 46.6% of the perindopril-treated patients (p < 0.05). It is concluded that telmisartan and perindopril both produce significant reductions in clinic SBP and DBP, but the mean reduction in ambulatory DBP during the last 8 h of the dosing interval is greater in patients treated with telmisartan.     

阿利沙坦酯治疗老年高血压的疗效观察

目的观察阿利沙坦酯治疗老年轻中度原发性高血压的有效性及安全性。方法选取老年轻中度原发性高血压患者60例,男性36例,女性24例,按1∶1∶1的比例随机分为3组,阿利沙坦酯80 mg 组20例、阿利沙坦酯160 mg 组20例、厄贝沙坦150 mg 组20例,入选患者治疗12周。结果治疗12周后三组患者收缩压及舒张水平较基线均明显下降,阿利沙坦酯80 mg 组、阿利沙坦酯160 mg 组、厄贝沙坦150 mg 组收缩压／舒张压分别降低13．8／7．9 mm Hg、14．5／7．3 mm Hg 及15．3／8．8 mm Hg,各血压组内不同时间点差异有统计学意义（P ＜0．05）,各血压组间差异无统计学意义（P ＞0．05）。结论阿利沙坦酯应用于老年轻中度原发性高血压安全有效。     

Comparative efficacy of nicardipine hydrochloride and propranolol in the treatment of hypertension

Nicardipine hydrochloride and propranolol were compared for antihypertensive efficacy and safety in a 14-week randomized, double-blind, crossover study. After taking placebo for 4 weeks, patients received either nicardipine (30 mg three times a day) or propranolol (40 mg three times a day) for 4 weeks, then placebo for 2 weeks and, finally, were crossed over to the alternative active medication for 4 weeks. Both drugs substantially reduced blood pressure. Statistically significant treatment effects favouring nicardipine were observed for supine and standing diastolic and systolic blood pressures. As expected, heart rate decreased significantly with propranolol, but not with nicardipine. Of the 33 patients evaluated for safety, 18 reported adverse experiences (two while taking placebo) that were assessed as probably related to the drugs under study. Symptoms related to vasodilation were reported more frequently during nicardipine treatment and respiratory complaints were more frequent in patients given propranolol.     

The efficacy of calcium antagonists in circulatory failure in elderly patients with hypertension

As many as 52 patients with essential hypertension aggravated by circulatory failure were examined for the clinical, hemodynamic and neurohumoral parameters during furosemide stimulation. In elderly patients, the optimal vasodilatory dose of nifedipine amounted to 10 mg, that of verapamil to 40 mg per os or to 5 mg i.v. In patients with the stimulated activity of plasma renin, the concentration of plasma aldosterone remained unchanged. The plasma concentrations of ACTH and cortisol tended towards increase while vasopressin concentration dropped. Side effects could be frequently observed. Hemodynamic shifts appeared to be negative. During the first hour, forced diuresis was recorded. In patients with unstimulated plasma renin activity, plasma aldosterone concentration declined, whereas the concentrations of ACTH, cortisol and vasopressin rose. Side effects were less in number, the hemodynamic shifts were positive, and diuresis turned out 2-3 times less during the first hour than within the next 4 hours. It is suggested that the efficacy of the treatment with calcium antagonists can be predicted according to the magnitude of the hourly diuresis with regard to the type of hemodynamics.     

The efficacy and safety of telmisartan compared to enalapril in patients with severe hypertension

This 8-week, open-label study compared the efficacy and safety of once-daily telmisartan, either alone or in combination with hydrochlorothiazide (HCTZ) and amlodipine, with a similar enalapril regimen in patients with severe hypertension. Clinically relevant reductions in supine systolic blood pressure/DBP were observed with telmisartan (14.6/13.2 mmHg) and enalapril (13.0/12.9 mmHg) monotherapy. Incremental reductions were seen with up-titration of monotherapy (telmisartan 8.1/7.4 and enalapril 9.2/7.7 mmHg), and the addition of HCTZ (telmisartan 14.9/8.7 and enalapril 8.0/6.7 mmHg), and amlodipine (telmisartan 8.0/6.5 and enalapril 10.5/6.4). After 8 weeks of treatment, supine DBP control was achieved in 55% and 35% of the patients on the telmisartan and enalapril regimens, respectively. Both treatment regimens were well tolerated. Telmisartan, a new angiotensin receptor blocker, is a safe and effective drug to use in combination for the treatment of patients with severe hypertension and proved at least as effective as the enalapril combination.     

Comparable efficacy and superior gastrointestinal tolerability (nausea,vomiting, constipation) of tapentadol compared with oxycodone hydrochloride

Introduction  

Two randomized, double-blind, placebo-controlled studies in acute and chronic pain treatment, powered to assess noninferiority of the efficacy of tapentadol immediate release (IR) (50 mg, 75 mg) versus oxycodone hydrochloride (HCl) IR (10 mg), established comparable efficacy of tapentadol IR with oxycodone HCl IR, and suggested tapentadol IR’s improved gastrointestinal tolerability. The impact of these equianalgesic doses of tapentadol and oxycodone HCl on bowel function and gastrointestinal tolerability was then directly assessed in the current study, using a validated bowel function diary to comprehensively assess opioid-induced constipation symptoms and outcomes.     

Safety and efficacy of sibutramine in overweight Hispanic patients with hypertension

This 6-month randomized study evaluated the safety and efficacy of sibutramine in 57 overweight Hispanic patients with hypertension. Following a 2-week washout to confirm the diagnosis of hypertension, antihypertensive medication was adjusted to achieve a blood pressure less than 140/90 mm Hg before institution of either sibutramine 10 mg or placebo once a day. A body mass index in excess of 27 kg/m² was required for entry. At study end, weight had changed from 75.4±9.6 to 70.0±9.5 kg in the sibutramine group and from 77.9±9.0 to 74.5±9.4 kg in the placebo group. In the sibutramine group, systolic blood pressure was 127.8±5.8 mm Hg after stabilization and 125.2±8.5 mm Hg after completion of the trial; respective values for diastolic blood pressure were 82.4±3.7 and 81.5±4.6 mm Hg. With placebo, blood pressure dropped from 129.0±7.1/80.9±4.9 mm Hg to 122.8±9.7/80.3±5.4 mm Hg at the same timepoints. In the sibutramine group, 14 patients reported 21 adverse events, most frequently headache (n=5), constipation (n=4), and dry mouth (n=4). In the placebo group, 13 patients had 20 adverse events. Sibutramine is safe and effective in overweight Hispanic patients with hypertension, but monitoring of blood pressure and titration of antihypertensive medication are necessary.     

Therapy of arterial hypertension with verapamil hydrochloride in patients after myocardial revascularization

Verapamil hydrochloride, a calcium blocker from a group of phenyl alkylamines, was tested for its effect on central hemodynamics (CH) and blood oxygen-transporting function (BOTF) in 14 patients with arterial hypertension after surgical myocardial revascularization. CH and BOTF were studied by using a Swan-Hanz catheter and directly measuring blood pressure (BP). There was a significant reduction in BPmean, total peripheral vascular resistance index, left ventricular stroke outcome index, and oxygen delivery index. Verapamil in an average dose of 80.4 +/- 18.02 mg at the injection rate of 24.6 +/- 3.9 micrograms/kg/min was shown to make BPmean normal 16.8 +/- 6.35 min later. The agent is comparable with other calcium blockers, such as nifedipine and isradipine in its action on CH and BOTF, as well as in its efficiency and safety.     

Efficacy,safety, and tolerability of valsartan/hydrochlorothiazide in Asian patients with essential hypertension

Introduction  

Previous studies have demonstrated that hypertensive patients need concomitant therapy with one or more drugs from different classes of antihypertensive agents to achieve their blood pressure control targets. We performed the first multinational observational study of valsartan/hydrochlorothiazide (HCTZ) single pill combination in Asia to determine the efficacy, safety, and tolerability in hypertensive patients. The objective of this multinational, multicenter, 24-week follow-up observational study is to evaluate the efficacy, safety, and tolerability of valsartan/hydrochlorothiazide single pill combination in the treatment of essential hypertension in the Asia-Pacific region.