Hyperkalemia - frequency in a group of hypertensive diabetics

To evaluate the frequency of hyperkalemia in a cohort of hypertensive diabetic patients. A prospective analytical cohort study. The study was carried out in department of medicine [nephrology] Military Hospital [MH] and Armed Forces Institute of Urology [AFIU] Rawalpindi from Jun 2007 - Jun 2009. A total of 110 hypertensive, middle aged diabetic patients attending medical OPD in MH and AFIU. Rawalpindi were followed over two years from Jun 2007 - Jun 2009 for development of hyperkalemia and monitored for changes in eGFR, Serum Urea, creatinine and blood glucose random besides changes in blood pressure and ECG findings. SPSS version 13 was employed for statistical analysis. During the course of study 9 patients were lost to follow up. There were 7 deaths among study subjects before the end of study after about ten to twelve months. Out of the 94 patients followed up mean Serum Urea at the end of study was 13.50 mmol/l against a serum creatinine level of 2.26mmol/l and an estimated GFR of 21.08 ml/ min. The frequency of raised serum Potassium of 5.1-6.0 mmol/l was 46.08% and 26.59% of the patients had serum Potassium of 6.1-7.2 mmol/l at the end of study. This was against an initial level of 4.5-5.0 mmol/l in 100% of the study subjects. Paired sample t-test revealed significant changes in each variable studied but a borderline positive correlation of 0.619 was observed only between serum potassium and change in eGFR at the end of study. The mean blood glucose random dropped from 16.14 mmol/l to 10.41 mmol/l. at the end of study mean systolic BP was 122mm Hg and diastolic BP 80.2mm Hg. The ECG revealed tall T waves in 64.9% of cases while at the start of study all subjects had their electrocardiograms within normal limits. There was a trend of increase in frequency of tall T waves with the rise of serum potassium levels. Raised serum potassium is a significant potential complication among long standing diabetics with covert nephropathy treated with ACE inhibotrs, ARBs, potassium sparing diuretics or a combination of these drugs. Co morbidities and development of this complication must therefore be considered by physicians when dealing with such patients

Aldose Reductase Inhibitor Ameliorates Renal Vascular Endothelial Growth Factor Expression in Streptozotocin-Induced Diabetic Rats

PURPOSE: The vascular endothelial growth factor (VEGF) expression of podocyte is one of the well-known major factors in development of diabetic nephropathy. In this study, we investigated the effects of aldose reductase inhibitor, fidarestat on diabetic nephropathy, and renal VEGF expression in a type 1 diabetic rat model. MATERIALS AND METHODS: Twenty four Sprague-Dawley male rats which were performed intraperitoneal injection of streptozotocin and normal six rats were divided into four groups including a normal control group, untreated diabetic control group, aldose reductase (AR) inhibitor (fidarestat, 16 mg.kg(-1).day(-1)) treated diabetic group, and angiotensin receptor blocker (losartan, 20 mg.kg(-1).day(-1)) treated diabetic group. We checked body weights and blood glucose levels monthly and measured urine albumin-creatinine ratio (ACR) at 8 and 32 weeks. We extracted the kidney to examine the renal morphology and VEGF expressions. RESULTS: The ACR decreased in fidarestat and losartan treated diabetic rat groups than in untreated diabetic group (24.79 +/- 11.12, 16.11 +/- 9.95, and 84.85 +/- 91.19, p < 0.05). The renal VEGF messenger RNA (mRNA) and protein expression were significantly decreased in the fidarestat and losartan treated diabetic rat groups than in the diabetic control group. CONCLUSION: We suggested that aldose reductase inhibitor may have preventive effect on diabetic nephropathy by reducing renal VEGF overexpression.

Management of steroid resistant nephrotic syndrome.

JUSTIFICATION: There is a lack of evidence based guidelines for management of children with steroid resistant nephrotic syndrome (SRNS). PROCESS: Experts of the Indian Society of Pediatric Nephrology were involved in a two-stage process, the Delphi method followed by a structured face to face meeting, to formulate guidelines, based on current practices and available evidence, on management of these children. Agreement of at least 80% participants formed an opinion. OBJECTIVES: To develop specific, realistic, evidence based criteria for management of children with idiopathic SRNS. RECOMMENDATIONS: The Expert Group emphasized that while all patients with SRNS should initially be referred to a pediatric nephrologist for evaluation, the subsequent care might be collaborative involving the primary pediatrician and the nephrologist. Following the diagnosis of SRNS (lack of remission despite treatment with prednisolone at 2 mg/kg/day for 4 weeks), all patients (with initial or late resistance) should undergo a renal biopsy, before instituting specific treatment. Patients with idiopathic SRNS secondary to minimal change disease or focal segmental glomerulosclerosis should receive similar therapy. Effective regimens include treatment with calcineurin inhibitors (tacrolimus, cyclosporine), intra-venous cyclophosphamide or a combination of pulse corticosteroids with oral cyclophosphamide, and tapering doses of alternate day corticosteroids. Supportive management comprises of, when indicated, therapy with angiotensin converting enzyme inhibitors and statins. It is expected that these guidelines shall enable standardization of care for patients with SRNS in the country.

Effect of angiotensin II on blood flow in acute and chronically inflamed knee joints of rabbits: the role of nitric oxide

Angiotensin converting enzyme [ACE] upregulation in stromal cells of joints affected by rheumatoid arthritis may lead to higher tissue angiotensin II that is a vasoconstrictor and mitogen factor. To date, the role of angiotensin II on regulating blood flow in inflamed joints has not been studied. Acute and chronic joint inflammation was induced in rabbits by intra-articular injection of carrageenan and antigen-induced arthritis method, respectively. The ACE level of synovial fluid and the response of joint blood flow to angiotensin II, angiotensin II receptor antagonist, and the role of nitric oxide [NO] in modulation of the effects of angiotensin II on joint blood vessels were examined The synovial fluid level of ACE was significantly increased during the process of inflammation and angiotensin II increased joint vascular resistance dose-dependently in both acute and chronically inflamed joints. The angiotensin 1 receptor antagonist losartan completely blocked the vasoconstrictor effect of angiotensin II on joint blood vessels and induced vasodilatation. Nitric oxide synthase inhibitor N-omega -nitro L- arginine methyl ester [L-NAME] increased joint vascular resistance and augmented vascular response of inflamed joints to angiotensin II. Angiotensin II receptors in joint blood vessels are angiotensin -1 subtype, and inflammation significantly increases the activity of synovial fluid ACE. Nitric oxide plays a significant role on regulating joint blood flow and in modulation of angiotensin 1 receptor-mediated vasoconstriction of inflamed joint blood vessels

study of prescribing valsartan in out-patient clinics at the Royal hospital, Muscat, Oman

Angiotensin Receptor Blockers such as Valsartan, are a newer class of drugs associated with significant reductions in cardiovascular morbidity and mortality. They are commonly used in hypertension, chronic heart failure, diabetes-related nephropathy and post-myocardial infarction in patients who are intolerant to Angiotensin Converting Enzyme inhibitors [ACEi], A review of medicines used in Royal Hospital [an Omani tertiary health care centre] during 2004 and 2005 showed that Valsartan was one of 20 most expensive drugs used The main objective of this study was to evaluate the pattern of prescribing valsartan in out-patient clinics. a retrospective study applying medicines use evaluation, to describe the pattern of prescribing Valsartan in comparison with international guidelines. The study carried out in the outpatient pharmacy setting, Royal Hospital from 15th May to 30th June 2006, It included 120 adult patients who had been prescribed Valsartan at the outpatient clinics during the study period, among the 120 patients only 109 patients were finally included in the study, Elevenpatients who had had duplicated prescriptionswere excluded from the study, 78% of the patients were on Valsartan for its FDA-approved indications while 22% of patients were for other non-approved indications. Half of the patients were initiated on an ACEi before shifting to Valsartan, The other half of the patients was started with Valsartan as a first line choice without any clinical justification, The study showed that half of the patients were initiated on Valsartan without being prescribed an ACEi prior to that, while the recommendation in most of the international guidelines based on indication stated that ARBs are used in patients who are intolerant to ACEi, The study emphasizes the need for further research to highlight the need for developing national guidelines and adhering to these guidelines for rational prescribing

Recent update in the management of hypertension.

Hypertension is still the leading cause of death worldwide. Hypertension increases not only the risk for progression of chronic kidney disease (CKD) but also for cardiovascular (CV) morbidity and mortality. For most patients it is the systolic blood pressure rather than the diastolic blood pressure that most strongly predicts adverse events. The optimal target for BP control for most hypertensive patients is < 140/90 mmHg, or < 130/80 mmHg for patients with diabetes and CKD. Certain lifestyle measures such as weight reduction, smoking cessation, restriction of dietary sodium intake, moderation of alcohol intake and an increase in physical activity can lower BP. Except for progression of proteinuric kidney disease and congestive heart failure (CHF), it is the achieved BP and not the class of agent that is most important in reducing morbid outcomes. If BP is more than 20/10 mmHg above the goal, therapy should be initiated with 2 drugs, one of which should be a thiazide-type diuretic. A strong consideration should be given to initiate antihypertensive therapy in patients with (RAAS) blockers, usually in concert with diuretics. Patients with proteinuria > 1 g/day despite optimal BP control with angiotensin-converting enzyme (ACE) inhibitor or angiotensin receptor blocker (ARB) monotherapy may benefit from a combination therapy.

role of renin blockers in the prevention of diabetes

To evaluate the role of renin blockers angiotensin converting enzymes inhibitors [ACEI] or angiotensin receptor blockers [ARB] in the prevention of diabetes. We did a meta-analysis using the Cochrane group methodology of all available randomized controlled trials [RCTs] that evaluated the role of renin blockers in which outcomes of new-onset diabetes was reported. This meta-analysis was conducted between April 2005-April 2006 at King Faisal Specialist Hospital and Research Center, Riyadh, Kingdom of Saudi Arabia. Thirteen trials including 91,388 individuals met the inclusion criteria. There was a statistically significant reduction in the incidence of new-onset diabetes in patients receiving renin blockers compared to other antihypertensive agents [relative risks=0.79; 95% confidence interval=0.75-0.84]. There was a statistically significant reduction in the incidence of new-onset diabetes in patients receiving renin-blockers compared to diuretics, conventional antihypertensive therapy [diuretics or beta-blockers], and calcium channel blockers. Renin blockers reduce the incidence of new-onset diabetes and should be considered as first line therapy, when indicated, in patients at high risk for diabetes

Angiotensin converting enzyme inhibitors impair recombinant human erythropoietin induced erythropoiesis in patients with chronic renal failure

To investigate the effects of angiotensin converting enzyme [ACE] inhibitors/angiotensin receptor blockers [ARBs] and other anti-hypertensive agents on recombinant human erythropoietin [rHuEPO] in chronic renal failure [CRF] patients. The present study was conducted at the Nephrology Department, Khan Research Laboratories Hospital and Quaid-i-Azam University, Islamabad, Pakistan during March 2004 to February 2005. One hundred patients, 55 males and 45 females [age range 13-78 years] were divided into 2 groups. Group-I patients received rHuEPO and ACE inhibitors/ARBs while Group-II patients received rHuEPO with other antihypertensives such as calcium channel blockers or beta-adrenergic receptor blockers. Monthly increment in hematocrit [HCT%] was monitored in both groups for 4 continuous months. One-way ANOVA on Dunn's, univariate and multivariate analyses were carried out to determine any significant improvement in erythropoiesis between the 2 treatment groups. Monthly increase in HCT% was significantly greater in the group that was treated with rHuEPO and antihypertensives other than ACE inhibitors/ARBs compared with that treated with ACE inhibitors/ARBs, an effect observed even at a higher dose of rHuEPO, and the patients were iron replete. The present data from our population confirms that ACE inhibitors/ARBs interfere with rHuEPO therapy for treatment of anemia in CRF. The ACE inhibitors/ARBs inhibit erythropoiesis induced by rHuEPO in CRF patients, therefore, simultaneous use of ACE inhibitors/ARBs and rHuEPO should be carried out with caution

Angiotensin-II behaves as an endogenous pro-inflammatory molecule.

Angiotensin-II regulates vascular tone, stimulates the release of pro-inflammatory cytokines, activates NF-kappaB, increases oxidant stress, and suppresses nitric oxide synthesis, and thus, it functions as an inflammatory molecule. Since ACE is present in many tissues, this suggests that angiotensin-II may play a significant role in atherosclerosis, congestive cardiac failure, stroke, bipolar disorder, schizophrenia, dementia, Alzheimer's disease, psoriasis, atopic and non-atopic dermatitis, eczema, several acute and chronic inflammatory diseases, and cancer, conditions in which inflammation is an aetiopathogenic factor. Thus, ACE inhibitors and/or angiotensin-II receptor blockers could be of benefit in these conditions. Furthermore, structural analogues of ACE inhibitors and angiotensin-II receptor blockers could be developed that possess anti-inflammatory actions without significant action on the cardiovascular system.

Effect of the combination of angiotensin receptor [AR] inhibitor and statin in patients with diabetic nephropathy

Despite the covencing evidence that antihypertensive treatment particularly with angiotensin converting enzyme [ACE] inhibitor, and angiotensin receptor [AR] blocker intrferes with renal disease progression, progression still cannot be completely halted, and there is a dire need for additional therapeutic intervention. Several studies have revealed the effects of statins in diabetic nephropathy. Therefore we evaluate the short-term effect of the combination of AR blocker [valsartan] and statin [simvastatin] in patients with DN. We included 24 normolipidemic patients with diabetic nephropathy. 9 of them are type I diabetes mellitus [DM], and 15 of them are type 2 DM. Each patient followed up for 3 months on valsartan [160mg /day], then for 6 months with addition of simvastatin [20 mg /day]. In simvastatin treatment' patients, proteinuria was significantly reduced by 56% [from 1242 +/- 524 to 553 +/- 314, p<0.0001] compared with baseline values. The present study demonstrates that statin [simvastatin] administration was associated with further reduction of proteinuria in normolipidemic diabetic patient already on AR blocker [valsartan]

Efecto de candesartán cilexetilo más hidroclorotiazida en la presión arterial ambulatoria de 24 horas en pacientes con hipertensión arterial asencial / The effect of candersartan cilexetil pul hydrochlorotiazide (HCT) in the 24 hours ambulatory blood pressure measurement of essential hypertensive patients

El monitoreo ambulatorio de presión arterial MAPA, permite conocer si el tratamiento antihipertensivo asegura una disminución homogénea y balanceada de las PA en cada hora de las 24 h del estudio. Objetivo: Evaluar la reducción de las PA con candesartán cilexetilo, un bloqueador de última generación altamente selectivo del receptor AT1 de la angiotensina II, por medio del índice de Homogeneidad (IH) obtenido del MAPA de 24 h y comparar este índice con clásico T/P ratio o relación valle/pico. Material y métodos: 23 pacientes con hipertensión arterial esencial con edad media de 51 ± 7 años recibieron dosis crecientes de candesartán cilexetilo 8 a 32 mg, más 12,5 mg de HCT, hasta completar 3 meses de tratamiento realizándose el segundo MAPA. Resultados: Candesartán cilexetilo en dosis promedio de 21 ± 7 mg más 12,5 mg de HCT redujo significativamente p <0,001 las PA sistólica en 31 ± 17 mmHg y la diastólica en 18 ± 7 mmHg durante el día y en la noche la reducción fue para la PAS de 27 ± 15 mmHg y para la PAD de 16 ± 9 mmHg. El (IH) Δ H/DS durante las 24 h fue para PAS de 2,16 ± 1,16 y para la PAD de 1,84 ± 0,87. El T/P sistólico fue de 68 ± 19 y el diastólico de 67 ± 21. El coeficiente relación lineal del IH sistólico con las reducciones de las PAS fue de r: 0,91 y p <0,001 y el IH diastólico con las reducciones de PAD r: 0,84 y p <0,001. La correlación del T/P sistólico y la reducción de las PAS fue r: 0,24 y p <0,25 y del T/P diastólico r: 0,19 y p <0,37. Conclusión: En pacientes con hipertensión arterial esencial documentada por el MAPA de 24 h, candersatán cilexetilo en dosis de 21 mg más 12,5 mg de HCT redujo significativamente p <0,001 las PA S y D durante el día y la noche, reducción homogénea y sostenida confirmada por el estudio del (IH) lo cual no pudo ser corroborado por clásico T/R ratio. Los promedios de PA durante el día fueron de 120/82 mmHg y durante la noche de 107/69 mmHg.

Additive Antiproteinuric Effect of Combination Therapy with ACE Inhibitor and Angiotensin II Receptor Antagonist: Differential Short-term Response between IgA Nephropathy and Diabetic Nephropathy

In previous studies, the synergistic antiproteinuric effect of the combination therapy of ACE inhibitors and angiotensin II receptor antagonists (ATRAs) has been inconsistent in relation to underlying renal diseases. The influence from the blood pressure (BP) - reducing effect in some studies might also contribute to this inconclusiveness. To examine the possibility of the benefit being different according to underlying renal diseases, we undertook a crossover therapeutic trial of the combination therapy in two selected homogenous groups of patients with diabetic and non-diabetic renal diseases. The BP-reducing effect was excluded during the study. Nineteen biopsy-proven IgA nephropathy, as examples of non-diabetic renal diseases, and 24 type 2 diabetic nephropathy patients were selected as the study subjects. The subjects had to meet the follow criteria: a creatinine clearance (Ccr) between 25 - 90 ml/min/1.73 m2, 24-hr urinary protein excretion rate over 1.0 g/day and a BP maintained at less than 130/80 mmHg, with more than six-month therapy of ramipril, (5.7 +/- 0.4 mg/day, 13 +/- 2 month). The baseline data between the two groups showed no significantly differences. After a 12-week stabilization period (control period), 4 mg, once daily, dose of candesartan (combination period) followed by a placebo (placebo period), or vice versa, were administered in addition to the ramipril, for 12 weeks. The combination, with candesartan, did not change the Ccr, BP, serum and urinary electrolytes or the urea. The 24 hour urinary protein excretion rate was significantly reduced by the combination therapy in the patients with IgA nephropathy (3.1 +/- 0.3 g/day in combination, 4.2 +/- 0.3 in control, and 4.3 +/- 0.2 in placebo; p < 0.05). However, the patients with diabetic nephropathy showed no reduction in their proteinuria with the combination therapy (3.8 +/- 0.2 g/day in combination, 3.9 +/- 0.3 in control, and 4.1 +/- 0.3 in placebo; p=NS). The changes in proteinuria showed no relationship with the changes in the BP in IgA nephropathy. In conclusions, the benefit of combination therapy of its antiproteinuric effect was different between IgA and diabetic nephropathy over the 12-week trial. The difference in the pathophysiological role, and the importance of the renin- angiotensin system, between the two diseases might contribute to the discrepancy in the result. We suggest the discrimination of the underlying renal diseases in the study subjects is an important prerequisite for future studies on this issue.

The efficacy and tolerability of an angiotensin II receptor blocker, telmisartan, in Thai patients with mild to moderate essential hypertension.

This open-labeled single-blinded study was performed to evaluate the efficacy and tolerability of telmisartan in the treatment of mild to moderate essential hypertension. Each patient was assigned to take a placebo for 4 weeks followed by once daily-titrated telmisartan (40-80 mg) for 8 weeks. "Office BP" and "24-hour ambulatory BP" measurements (24-h ABPM) were recorded as scheduled. Thirty-one patients (10 males: 21 females) with a mean age of 48.1 years were enrolled. The final SBP/DBP reductions of 14.6 +/- 14.2/9.9 +/- 6.2 mm Hg were obtained. Full response defined as office DBP reduction of > or = 10 mm Hg from baseline and/or DBP < 90 mm Hg was achieved in 73.3 per cent of cases. Excluding 5 cases of white coat HT diagnosed by 24-h ABPM, full response rate (DBP reduction of > or = 10 mm Hg from baseline and/or < 85 mm Hg) was 76 per cent. Trough to peak ratio and smoothness index for SBP/DBP were highly acceptable (0.75/0.76 and 0.97/1.01, respectively). There were 4 cases of adverse events (2 cases of dizziness, 1 case of headache, and 1 case of acute myocardial infarction).

Inducible Nitric Oxide Synthase (iNOS) Expression Is Increased in Lipopolysaccharide (LPS)-Stimulated Diabetic Rat Glomeruli: Effect of ACE Inhibitor and Angiotensin II Receptor Blocker

Previously, we reported that high glucose enhanced cytokine-induced nitric oxide (NO) production by rat mesangial cells (MCs), and that the enhanced expression of the iNOS pathway may promote extracellular matrix accumulation by MCs. The present study was designed to examine whether the iNOS pathway is pathologically altered in experimental diabetic nephropathy, and whether therapy with angiotensin converting enzyme (ACE) inhibitor (imidapril: I) or angiotensin II type I receptor (AT1) blocker (L-158,809: L), ameliorates these changes. Male Sprague-Dawley rats were injected with diluent (control: C) or streptozotocin. At sacrifice after 4, 8 and 12 weeks, rats underwent either a 4 hour placebo or an intraperitoneal lipopolysaccharide (LPS, 2 mg/kg) challenge. Systolic blood pressure (SBP) and urinary protein excretion (UPE) increased significantly in diabetic (D) rats compared with C. The basal expression of glomerular iNOS mRNA was increased in D rats compared with that of C rats, by reverse- transcription (RT)-polymerase chain reaction (PCR), whereas there was no significant difference in the level of protein by Western blot analysis. Upon LPS stimulation, the iNOS mRNA and protein expression was significantly elevated in D rats. In D rats, this up-regulation, of LPS-stimulated iNOS expression, was equally ameliorated both by I and L in mRNA and protein levels. From immunohistochemistry (IHC), there was a negative staining for the iNOS within the glomeruli of five C rats without LPS treatment, but one of four rats, with LPS treatment, showed minimal iNOS staining in the glomeruli. In D rats, the glomerular mesangium and podocytes were positive for iNOS in each of three out of five rats with, and without, LPS treatment. In conclusion, LPS-stimulated glomerular iNOS expression was enhanced in diabetic pnephropathy, and the activation of angiotensin II may play a role in this enhancement.

Assessment of effect of angiotensin II receptor antagonist losartan on aortic distensibility in patients with essential hypertension by echocardiography / 华中科技大学学报（医学）（英德文版）

The effects of angiotensin II receptor antagonist losartan on elastic properties of aorta in patients with mild to moderate essential hypertension were assessed. The ascending aortic distensibility in 26 patients (48 +/- 3 years) with mild to moderate essential hypertension before and after 12 weeks of treatment with losartan (50 mg/day) was evaluated by using two-dimensional echocardiography. M-mode measurements of aortic systolic (Ds) and diastolic diameter (Dd) were taken at a level approximately 3 cm above the aortic valve. Simultaneously, cuff brachial artery systolic (SBP) and diastolic (DBP) pressures were measured. Aortic pressure-strain elastic modulus (Ep) was calculated as Dd x (SBP-DBP)/(Ds-Dd) x 1333 and stiffness index beta (beta) was defined as Dd x Ln (SBP/DBP)/(Ds-Dd). Blood pressure significantly decreased from 148 +/- 13/95 +/- 9 mmHg to 138 +/- 12/88 +/- 8 mmHg (systolic blood pressure, P = 0.001; diastolic blood pressure, P = 0.003). There was no significant difference in pulse pressure before and after treatment with losartan (53 +/- 10 mmHg vs 50 +/- 7 mmHg). The distensibility of ascending aorta increased significantly as showed by the significant decrease in pressure-strain elastic modulus from 4.42 +/- 5.79 x 10(6) dynes/cm2 to 1.99 +/- 1.49 x 10(6) dynes/cm2 (P = 0.02) and stiffness index beta from 27.4 +/- 32.9 to 13.3 +/- 9.9 (P = 0.02). Although there was a weak correlation between the percent changes in pressure-strain elastic modulus and stiffness index beta and that in diastolic blood pressure after losartan treatment (r = 0.40, P = 0.04 and r = 0.55, P = 0.004, respectively), no correlation was found between the percent changes in pressure-strain elastic modulus and stiffness index beta and that in systolic blood pressure (r = 0.04, P = 0.8 and r = 0.24, P = 0.2, respectively). Our study demonstrated that angiotensin II receptor antagonist losartan has a beneficial effect on aortic distensibility in patients with mild to moderate essential hypertension and this effect is partly independent of blood pressure reduction.

Study on the pharmacokinetics and relative bioavailability of irbesartan capsules in healthy volunteers / 华中科技大学学报（医学）（英德文版）

The pharmacokinetics and relative bioavailability were studied in 18 healthy volunteers. A single oral dose of 150 mg irbesartan capsule (test) or tablet (reference) was given to each volunteer according to a randomized 2-way crossover study. The concentrations in plasma were determined by HPLC-UV method. The main parameters of irbesartan capsules were: Cmax: 1.502 +/- 0.295 micrograms/ml, tmax: 1.44 +/- 0.34 h, t 1/2: 20.21 +/- 14.71 h, AUC0-t: 11.087 +/- 3.443 micrograms/ml-1.h. The relative bioavailability of capsule to tablet was (101.4 +/- 28.9)%. The results of statistical analysis showed that two formulations were bioequivalent.