Pharmacokinetics of Intravenous and Oral Pindolol in Hypertensive Patients with Chronic Renal Failure

1978 ◽  
Vol 55 (s4) ◽  
pp. 275s-277s
Author(s):  
M. E. Safar ◽  
N. Ph. Chau ◽  
J. A. Levenson ◽  
A. Ch. Simon ◽  
Y. A. Weiss

1. The pharmacokinetics of intravenous and oral pindolol were determined in 24 hypertensive patients with normal or impaired renal function. 2. In patients with normal renal function, the total clearance of the drug was the sum of both the renal and non-renal clearances in equal parts. The non-renal clearance was found to equal the hepatic clearance directly measured from the hepatic extraction ratio and hepatic blood flow. 3. Compared with patients with normal renal function, patients with chronic renal failure exhibited (i) unchanged transfer rate constants and distribution volumes, (ii) decreased total body clearance with decreased renal clearance and unchanged non-renal clearance. 4. Analysis of data obtained after oral administration of the drug by the Loo—Riegelman method showed that the pindolol absorption kinetic was non-linear. Compared with patients with normal renal function, patients with chronic renal failure exhibited (i) a significantly decreased fraction of dose effectively absorbed, (ii) an increased initial rate of absorption. The initial rate of absorption was inversely correlated with creatinine clearance. 5. The study provided evidence that in patients with renal insufficiency, (i) no increase in the metabolism of the drug accompanied the decrease in renal function, and (ii) decreased bio-availability was associated with a reduced fraction of the dose effectively absorbed and an increased rate of absorption.

2004 ◽  
Vol 34 (1) ◽  
pp. 113-118 ◽  
Author(s):  
Glenda Ramalho Barbudo-Selmi ◽  
Marileda Bonafim Carvalho ◽  
André Luis Selmi ◽  
Silvio Emílio Cuevas Martins

The purpose of this study was to evaluate periodontal disease (PD) in dogs with chronic renal failure (CRF) and to compare it to PD in dogs with normal renal function (NRF). Twelve dogs with CRF and 24 dogs with NRF, all presenting dental pocket formation, were compared. In all dogs, serum creatinine, blood urea nitrogen, urine specific gravity and total red and white blood cells were determined. A complete oral examination was also performed including evaluation of bacterial plaque, gingivitis, gingival recession, pocket, calculus, dental mobility, dental loss, and ulcers. These data were used to calculate plaque index (PI), gingival index (GI) and periodontal destruction index (PDI). PD was graded as mild, moderate or severe based on the results. Mild, moderate or severe PD was observed in dogs with NRF, whereas dogs with CRF presented either mild or severe PD. Dogs with NRF showed higher involvement of the maxillary teeth, whereas dogs with CRF showed a higher involvement of the mandibular teeth. Plaque index was significantly higher in dogs with NRF. It was concluded that lesion distribution and periodontal disease progression may be altered in dogs with CRF, and gingival inflammatory response differs in dogs with NRF and CRF regarding to the stage of periodontal disease.


1991 ◽  
Vol 6 (4) ◽  
pp. 252-256 ◽  
Author(s):  
T. Hannedouche ◽  
R. Brouard ◽  
M. Godin ◽  
D. Kleinknecht ◽  
F. Paillard ◽  
...  

1993 ◽  
Vol 85 (6) ◽  
pp. 733-736 ◽  
Author(s):  
R. Rustom ◽  
J. S. Grime ◽  
P. Maltby ◽  
H. R. Stockdale ◽  
M. J. Jackson ◽  
...  

1. The new method developed to measure renal tubular degradation of small filtered proteins in patients with normal renal function, using radio-labelled aprotinin (Trasylol) (R. Rustom, J. S. Grime, P. Maltby, H. R. Stockdale, M. Critchley, J. M. Bone. Clin Sci 1992; 83, 289–94), was evaluated in patients with chronic renal failure. 2. Aprotinin was labelled with either 99mTc (40 MBq) or 131I (0.1 MBq), and injected intravenously in nine patients, with different renal pathologies. 51Cr-EDTA clearance (corrected for height and weight) was 40 + 5.4 (range 11.2-81) ml min−1 1.73 m−2. Activity in plasma and urine was measured over 24–48 h, and chromatography on Sephadex-G-25-M was used to separate labelled aprotinin from free 99mTcO4− or 131I−. Renal uptake was measured for 99mTc-labelled aprotinin only. 3. The volume of distribution was 20.2 + 2.3 litres. Chromatography showed all plasma activity as undegraded aprotinin, and urine activity only as the free labels (99mTcO4− or 131I−). 4. As in patients with normal renal function, activity in the kidney appeared promptly, with 5.7 + 2.5% of the dose detected even at 5 min. Activity rose rapidly to 9.4 + 1.6% of dose after 1.5 h, then more slowly to 15.0 + 0.5% of dose at 4.5 h, and even more slowly thereafter, reaching 24.1 + 2.8% of dose at 24 h. Extra-renal uptake was again insignificant, and both 99mTcO4− and 131I− appeared promptly in the urine, with similar and uniform rates of excretion over 24 h. 5. Both tubular uptake at 24 h and the rate of tubular metabolism over 24 h were lower than in the patients with normal renal function studied previously, but only the rate of tubular metabolism was directly related to the glomerular filtration rate (r = 0.75, P <0.02). 6. Correction for the reduced glomerular filtration rate yielded values for both tubular uptake (0.67 + 0.14 versus 0.32 + 0.03% of dose/ml of glomerular filtration rate, P <0.005), and tubular metabolism (0.033 + 0.07 versus 0.015 + 0.001% of dose h−1 ml−1 of glomerular filtration rate, P <0.005) that were higher by comparison with those for patients with normal renal function studied previously. 7. Fractional renal degradation of 99mTc-aprotinin (in h−1), derived from the mean rate of urinary excretion of the free isotope over a given interval, divided by the mean cumulative kidney uptake over the same interval, also fell steeply early, and then more slowly to 0.07 + 0.01 h−1 at 14.25 h (between 4.5 and 24 h). 8. It is concluded that the method described previously is also suitable in patients with chronic renal failure, allowing further research into renal disease progression.


1980 ◽  
Vol 79 (1) ◽  
pp. 26-34 ◽  
Author(s):  
Herta Spencer ◽  
Margaret Lesniak ◽  
Carol A. Gatza ◽  
Dace Osis ◽  
Menahem Lender

1979 ◽  
Vol 57 (s5) ◽  
pp. 383s-385s ◽  
Author(s):  
G. S. Stokes ◽  
J. C. Monaghan ◽  
G. W. Frost ◽  
E. P. MacCarthy

1. The fall in blood pressure produced by a test dose of prazosin was greater in a group of patients with chronic renal failure than in a group with normal renal function. 2. This difference could not be attributed to increased reactivity, measured as the slope of the regression line relating mean blood pressure and plasma prazosin concentration, nor to retarded elimination of the drug. 3. The enhanced antihypertensive effect of prazosin in renal failure appears to reflect changes in the bioavailability or distribution of the drug, which result in higher drug concentrations for a given dose.


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