Biomedical subjects

E R Debusmann

Publications and source records attributed to E R Debusmann.

11 recordsLinked to original sources

PubMed2005

Use of LifeSite port systems for hemodialysis in Germany.

AIM: Studies haveshown lower infection rates of port systems compared to established, transcutaneous cuffed-tunneled dialysis catheters. This was shown in otherwise quite healthy patients starting hemodialysis treatment. It is unclear to what extent these results can be applied to countries such as Germany where, unlike the US, central venous access systems are used mainly for patients with a high comorbidity. We investigated complications in patients with exhausted access sites and a high comorbidity. METHOD: In a retrospective, representative multicenter study, 34 patients with a high rate of comorbidity were assessed. The age was 67.5 +/- 12.5 years, the median number of failed AV fistulas or AV grafts was 4 (0-18). RESULTS: The survival rate was 84.9%, 55.2% and 55.2% after 6, 12 and 24 months, respectively. The rate of local and systemic infections was 2.83 per 1,000 patient days. Thrombotic events occurred at a rate of 2.26 per 1,000 patient days. We did not see a statistically significant effect using 0.2% sodium oxychlorosene (n = 13) or 70% isopropyl alcohol solution (n = 21) as the antimicrobial solution used before opening the valve of the port with the dialysis needle. CONCLUSIONS: We showed that complications of hemodialysis treatment using LifeSite vascular access systems in patients with very high co-morbidity in Germany seem to occur less often than those reported for cuffed-tunneled catheters and were not more frequent than those reported for other patient groups using LifeSites in the US. Technical survival rates were encouraging for up to two years. LifeSite port systems might be a good or even better central venous access than cuffed-tunneled catheters for patients in which an AV fistula or -graft is not possible.

Aged↗

PubMed1989

Pharmacokinetics of ramipril in hypertensive patients with renal insufficiency.

In an open trial, the pharmacokinetics of ramipril and its active metabolite ramiprilat were studied in 25 hypertensive patients with various degrees of renal insufficiency given 5 mg ramipril p.o. for 14 days. Ramipril was rapidly absorbed and reached a peak concentration after 1-2 h. Cmax was greater in patients with severe renal insufficiency, which might indicate a reduced renal elimination rate, although, the rapid decline of the concentration-time curve for ramipril was almost independent of renal function. The mean initial apparent half-lives on Days 1 and 12, respectively, were 2.8 and 3.4 h (Group I: creatinine clearance 5-15 ml/min), 1.8 and 2.3 h (Group II: creatinine clearance 15-40 ml/min), and 1.9 and 1.9 h (Group III: creatinine clearance 40-80 ml/min). No accumulation was observed after multiple dosing. In contrast, the kinetics of its active acid metabolite ramiprilat was significantly influenced by renal function. The mean times to the peak plasma concentration were 5.7 h in Group I, 4.4 h in Group II and 3.8 h in Group III. The initial decline in plasma ramiprilat was dependent upon renal function; the mean initial apparent half-lives (Days 1 and 12, respectively) were 16.0 and 14.8 h (Group I), 10.1 and 9.5 h (Group II) and 10.6 and 8.0 h (Group III). Mean trough concentrations and absolute accumulation also increased with worsening renal function, and the renal clearance of ramiprilat was significantly correlated with the creatinine clearance. The subsequent long terminal phase at low plasma ramiprilat concentrations represented slow dissociation of the ACE-inhibitor complex.(ABSTRACT TRUNCATED AT 250 WORDS)

Adult↗

PubMed1989

Pharmacodynamic effects of a single 10-mg dose of the angiotensin converting enzyme inhibitor ramipril in patients with impaired renal function.

A single oral 10-mg dose of ramipril, a long-acting angiotensin converting enzyme (ACE) inhibitor, was given to 24 hypertensive patients with different degrees of renal function. Creatinine clearance ranged from below 15 ml/min (n = 9) to above 80 ml/min (n = 3). Serial blood samples were taken for the determination of ACE activity, plasma renin activity (PRA), aldosterone (ALDO), angiotensin II (AT II), and serum creatinine (CR). Blood pressure was also monitored before and after medication. After administration of ramipril systolic and diastolic blood pressure (BP) fell; the decreases were unrelated to renal function. Peak BP-lowering effect was seen at 6 h basal, 174 +/- 19.5/102.6 +/- 8.9 to 149.8 +/- 19.7/87.6 +/- 13.3 mm Hg (mean +/- SD; p less than 0.001). ACE inhibition occurred within 2 h, being maximal at 4 h: basal, 82.6 +/- 17.9 to 0.2 +/- 0.6 nmol/ml/min (p less than 0.001). The greater the renal impairment, the longer the ACE inhibition. Angiotensin II was reduced maximally at 10 h after dosing, from 10.4 +/- 5.4 to 6.2 +/- 3.6 pg/ml (p less than 0.01). Aldosterone also fell from 212 +/- 188.4 to 134 +/- 73.3 pg/ml at 6 h (p less than 0.01). Plasma creatinine was unchanged: 401.3 +/- 315.7 to 394.9 +/- 306.1 nmol/L (NS). Ramipril, given as a single oral dose, lowers BP in hypertensives with both normal and impaired renal function, inhibits ACE activity, and causes no change in serum creatinine.

Adult↗

PubMed1989

Steady-state kinetics of ramipril in renal failure.

In an open trial, the pharmacokinetics of ramipril and its active metabolite ramiprilat were studied in 23 hypertensive patients with various degrees of renal insufficiency. During a 2-week treatment period, each subject took daily a 5-mg tablet of ramipril. Serum profiles and urinary excretion of the parent compound and ramiprilat, the active metabolite, were then evaluated. Peak concentrations of ramipril were slightly greater in patients with severe renal insufficiency; however, most of the ramipril was metabolized in the liver. The drug concentration-time curve was almost independent of renal function and no accumulation was observed after multiple dosing. In contrast, ramiprilat kinetics were significantly influenced by renal function. Initial apparent half-lives (8-16 h), mean trough concentrations (5-19 ng/ml), and absolute accumulation all increased with worsening renal function, and renal clearance of ramiprilat was significantly correlated with creatinine clearance. The subsequent long terminal phase at low ramiprilat serum concentration represents the slow dissociation of the angiotensin converting enzyme (ACE)-bound drug. This study indicates that in patients with severe renal insufficiency (creatinine clearance below 30 ml/min), smaller doses of ramipril will be required than in patients with normal or borderline normal renal function.

Adult↗

PubMed1989

Therapeutic efficacy and tolerance of ramipril in hypertensive patients with renal failure.

In an open trial, the antihypertensive and hormonal effects of ramipril, a new nonsulfhydryl angiotensin converting enzyme (ACE) inhibitor, were studied in 23 hypertensive patients with various degrees of renal failure: group I, creatinine clearance 5-15 ml/min, n = 10; group II, creatinine clearance 15-40 ml/min, n = 7; group III, creatinine clearance 40-80 ml/min, n = 6. In a 2-week placebo run-in period, antihypertensive agents were reduced or discontinued. During the treatment phase, patients received a 5-mg tablet of ramipril once daily for a period of 2 weeks. Concomitant medication remained unchanged. In all groups, ramipril significantly decreased mean arterial blood pressure. Blood pressure response was not different in the three groups, although plasma ramipril levels were higher in patients with severe renal failure. In patients with high plasma renin activity (PRA), reduction of blood pressure was greater than in subjects with low PRA. Plasma ACE activity was suppressed to less than 20% of its initial value in all groups during the whole treatment period, and the suppression was more marked and lasted longer in patients with severe renal failure. A strong correlation between the plasma ramiprilat levels and the inhibition of plasma ACE activity was noted for all groups. Mean serum creatinine did not increase significantly; serum potassium levels rose from 4.5 to 4.9 mmol/L on day 14 (p less than 0.01). In conclusion, in patients with various degrees of renal failure, ramipril represents an effective and well-tolerated antihypertensive agent.(ABSTRACT TRUNCATED AT 250 WORDS)

Adult↗

PubMed1987

Influence of renal function on the pharmacokinetics of ramipril (HOE 498).

The pharmacokinetics of ramipril (HOE 498) were studied after oral administration of a single 10 mg dose to 24 hypertensive patients with different degrees of renal function. The creatinine clearance ranged between 4.1 and 126 ml/min/1.73 m2 and was below 35 ml/min/1.73 m2 in 16 patients. Angiotensin converting enzyme activity and the concentrations of ramipril and its active diacid metabolite ramiprilat were measured in plasma up to 10 days after drug intake. Urine levels of ramipril, ramiprilat, their glucuronides and 2 major metabolites (a diketopiperazine and a diketopiperazine acid) were measured up to 4 days after medication. The plasma concentration-time curve of ramiprilat was polyphasic with an initial steep decline after the peak level and a subsequent very long terminal phase at low concentrations. Impaired renal function resulted in higher peak levels of ramiprilat, longer times to peak and a markedly slower decline of plasma ramiprilat levels. Hence, the duration of angiotensin converting enzyme inhibition was considerably prolonged in renal failure and depended on the severity of renal impairment. The urinary excretion of ramipril and its metabolites decreased with decreasing renal function and was linearly related to the creatinine clearance, suggesting an alternative pathway of elimination. The pattern of excretion rates of ramipril and its various metabolites was not affected by renal failure. In contrast to the marked changes in the renal elimination, no relevant differences were observed in the absorption of ramipril from the gastrointestinal tract. Systolic and diastolic blood pressure decreased in all groups. The single 10 mg dose of ramipril was well tolerated.

Adult↗

PubMed1970