No abstract

The metabolism of catecholamines (CA) in non-selected patients with chronic renal failure and under hemodialysis (CRFh) was studied by measuring the concentration of plasma free, sulfo- and glucuroconjugated CA, dopamine (DA), norepinephrine (NE), and epinephrine (EPI). Our data demonstrate a statistically significant increase of free DA and free NE concentration in CRFh, while that of free EPI was not different from controls. However a careful scrutiny of 35 individual data suggests that sub-groups of patients with either high normal or low plasma-free NE concentration could exist; this likely heterogeneity could be a good explanation for conflicting conclusions provided by previous reports. Suspecting that conjugated CA might be altered in CRFh, plasma sulfo- and glucuro-conjugated DA, NE and EPI were also measured. We have found a predictable and highly significant increase of sulfo-conjugated CA; plasma concentration of glucuro-conjugated DA and NE in CRFh was not different from controls, while that of glucuro-conjugated EPI was significantly increased. The physiological meaning, if any, of these new observations on conjugated CA cannot be assessed at the moment. The effects of hemodialysis were also investigated. Measurements on the arterial and on the venous line showed highly significant differences for tyrosine, free and sulfo-conjugated CA, and a lack of difference for glucuro-conjugated CA. Thus tyrosine, free and sulfo-conjugated CA were eliminated by the artificial kidney, but not glucuro-conjugated amines.(ABSTRACT TRUNCATED AT 250 WORDS)

The levels of free and sulfoconjugated catecholamines were measured in the plasma of fasting, recumbent normal subjects before and after an oral load of the catecholamine precursors tyrosine or L-dopa. Basal values of sulfoconjugated catecholamines, measured in plasma samples diluted 1:100 were 7998 +/- 540 pg/ml for dopamine sulfate, 2938 +/- 281 pg/ml for norepinephrine sulfate, and 2958 +/- 288 pg/ml for epinephrine sulfate (n = 37 tests in 15 men); these basal values are higher than those reported previously. Neither free nor sulfoconjugated catecholamine concentrations were changed by a tyrosine load (100 mg/kg) that induced a doubling of the plasma tyrosine level or by a meal low in phenylalanine and tyrosine (but otherwise supplying constituents of normal nourishment) that induced a greater than 50% reduction in the plasma tyrosine concentration. After an oral load of L-dopa (125 mg) the following were observed. (1) An extremely large increase (greater than 100-fold) in dopamine sulfate levels was noted, an increase that was less marked in the same subjects given L-dopa (125 mg) plus the peripheral dopa-decarboxylase inhibitor carbidopa (12.5 mg); as expected, free dopamine concentration also was increased. (2) Neither free nor sulfoconjugated norepinephrine concentrations were altered. (3) Epinephrine sulfate but not free epinephrine concentration was increased (more than ten-fold) after L-dopa ingestion alone; this result was unexpected and has to be confirmed before considering its physiological meaning, if any.

1 The pharmacokinetics of atenolol, after 200 mg orally, were studied in 18 patients with terminal renal insufficiency (creatinine clearance less than 5 ml/min), of whom twelve were being treated by chronic dialysis. 2 The peak plasma level, 1.59 +/‐ 0.43 mg/l, was reached in 4.7 +/‐ 2.1 h. 3 Without dialysis treatment, the apparent plasma half‐ life of atenolol was greatly increased (73.4 +/‐ 28.8 /). During dialysis, it dropped to 7.5 +/‐ 3.7 h but returned to 51.2 +/‐ 17.3 h after dialysis. The plasma atenolol plot was a rising slope for a few hours after the end of dialysis. 4 Renal clearance of atenolol was very low (4.6 +/‐ 1.5 ml/min). 5 Plasma clearance during dialysis was 42.6 +/‐ 21.3 ml/min for a mean blood flow‐rate of 236 +/‐ 25 ml/min through a cuprophane membrane dialyser. 6 These results suggest that dosage should be modified for these patients.

No abstract