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  • 1990-1994  (2)
  • ACE inhibitors  (1)
  • Calcium metabolism  (1)
  • 1
    ISSN: 1432-1440
    Keywords: Cyclosporin A ; 1,25-Dihydroxyvitamin D3 ; Calcium metabolism ; Parathyroid hormone
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Notes: Summary Animal studies have shown that cyclosporin A (CyA) stimulates renal 25-hydroxyvitamin D3 [25(OH)D3]-1α-hydroxylase activity; in contrast, studies in renal transplant recipients indirectly suggest that CyA reduces 1α,25-dihydroxyvitamin D3 [1,25 (OH)2D3] production. To clarify the effect of CyA on vitamin D metabolite concentrations, we measured parameters of calcium metabolism in 37 CyA-treated patients (median trough whole blood levels 171–222 ng/ml) with multiple sclerosis and initially normal kidney function. The patients participated in a randomized double-blind study to assess the efficacy of CyA in multiple sclerosis. An age- and sex-matched control group (n = 39) received azathioprine (Aza). Measurements were made at the end of a 2-year treatment period. The 1,25(OH)2D3 serum concentrations were not significantly different between the two groups, although they were numerically lower in CyA-treated patients [median (range), 28.4 pg/ml (7.8–85.9) vs 41.0 pg/ml (9.2–105.1) in Aza-treated patients]. The 25(OH)D3 levels were comparable in both groups. There was no correlation between the 25(OH)D3 and 1,25(OH)2D3 concentrations. The renal function in both groups was stable in the last 6 months of the study. At the end of the study period, the endogenous creatinine clearance was significantly lower in the CyA-treated group (85 ± 17 ml/min versus 99 ± 22 in the Aza-treated group, P 〈 0.05). The carboxyterminal parathyroid hormone (C-PTH) was within the normal range in both groups, although CyA-treated patients had significantly higher concentrations (P〈0.01). The urinary excretion of mineral ions, cations and protein was similar in both groups. Our data suggest that long-term treatment with CyA does not cause clinically important alterations of vitamin D metabolism in humans. Subtle differences in the concentrations of 1,25(OH)2D3 and C-PTH between CyA- and Aza-treated patients result presumably from a slight impairment of renal function through CyA.
    Type of Medium: Electronic Resource
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  • 2
    Electronic Resource
    Electronic Resource
    Springer
    European journal of clinical pharmacology 46 (1994), S. 537-543 
    ISSN: 1432-1041
    Keywords: Lisinopril ; Dose adjustment ; ACE inhibitors ; pharmacokinetics ; pharmacodynamics ; renal failure
    Source: Springer Online Journal Archives 1860-2000
    Topics: Chemistry and Pharmacology , Medicine
    Notes: Abstract To prevent drug accumulation and adverse effects the dose of hydrophilic angiotensin-converting enzyme (ACE) inhibitors, e. g. lisinopril, must be reduced in patients with renal failure. To obtain a rational basis for dose recommendations, we undertook a prospective clinical trial. After 15 days of lisinopril treatment pharmacokinetic and pharmacodynamic parameters were determined in patients with advanced renal failure (n=8; endogenous creatinine clearance [CLCR]: 18 ml·min−1·1.73m−2) and in healthy subjects with normal renal function (n=16; CLCR: 107 ml·min−1·1.73m−2). The volunteers received 10 mg lisinopril once daily, the daily dose in patients (1.1–2.2 mg) was adjusted to the individual CLCR according to the method of Dettli [13]. After 15 days of lisinopril treatment the mean maximal serum concentration (C max) in patients was lower than in volunteers (30.7 vs 40.7 ng·ml−1, while the mean area under the concentration-time curve (AUC 0–24 h) was higher (525 vs 473 ng·h−1·ml−1). ACE activity on day 15 was almost completely inhibited in both groups. Plasma renin activity, angiotensin I and angiotensin II levels documented marked inhibition of converting enzyme in volunteers and patients. Furthermore, average mean arterial blood pressure in patients decreased by 5 mmHg and proteinuria from 3.9–2.7 g per 24 h after 15 days of treatment with the reduced dose of lisinopril. Adjustment of the dose of lisinopril prevents significant accumulation of the drug in patients with advanced renal failure during chronic therapy. Mean serum levels did not exceed this in subjects with normal renal function receiving a standard dose. Despite substantial dose reduction, blood pressure and proteinuria decreases were observed.
    Type of Medium: Electronic Resource
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