Br. J. clin. Pharmac. (I 9 79), 7
LETTERS TO THE EDITORS
311
EFFECT OF URINARY,pH AND FLOW RATE ON CATECHOLAMINE EXCRETION Despite intensive investigations of factors influencing personnel. Ammonium chloride (0.1 g kg-' body urinary excretion of catecholamines, the effect of weight day-') and potassium citrate (8-10 g daily) urinary pH and urinary flow rate has been relatively were used for urinary acidification and alkalinization neglected. The urinary excretion of weakly acidic and respectively. Half received ammonium chloride basic drugs and of a number of endogenous followed I week later by the citrate, the other three compounds and monoamines is pH-dependent (Price received the drugs in reverse order. Two hour urinary 1975, 1976; Weiner & Mudge, 1964). specimens were collected daily for the 5 week days. In an analysis of the effect of pH on the biological The subjects emptied their bladders at 12.00 h then activity of the catecholamines in vivo, Lewis (1954) voided again in an acid-washed container at 14.00 h. observed that sympathomimetic amines are strong The subjects started taking the salt on Monday bases of pK, (amino) 9.4-10.8 and weak acids of pK, morning in divided specified dose (6 hourly) until the (phenolic) 8.8-9.5, that ionization does not account pH changes had reached 5-or 8 respectively. When for the difference in activity of these and that at this pH was attained the subject stopped the medicaphysiological pH the compounds exist almost wholly tion but continued to provide specimens for the rest of as cations (base). Lewis' (1954) measurements were the week. made at 20°C and values at 370C are slightly higher The urinary volume was measured and the pH (Armstrong & Barlow, 1976). Two factors further recorded using a pH meter. The catecholamines were complicate the pH effect on the activity of amines. assayed using a spectrofluorophotometric method First, pK, changes with the concentration of the (Carruthers, Taggart, Conway, Bates & Somerville, solution, decreasing with dilution of the amines. 1970). The limit of detection is 0.5 ng/ml for both Secondly, the amines tend to form zwitterions, with amines. negative and positive ions present simultaneously. But the chemical features which favour zwitterion pH and volume formation do not favour activity at a-adrenoceptors, nor is there a correlation with activity at /The mean urinary pH on the acid regimen differed adrenoceptors (Armstrong & Barlow, 1976). significantly from that on the alkaline (Table 1). Thus Some studies have touched on catecholamines. Levi the administration of potassium citrate and (1972) stated that Finholt & Stokke (1952) found that ammonium chloride had some effect, with a mean when urine becomes alkaline e.g., after hyperventiladifference of 1.66 units between pH values of the tion, catecholamine oxidation in the urine is subjects' two samples. There is also a significant but low positive correlation between the acid and alkaline accelerated. Townsend & Smith (1973) and Sandler, pH values for the subjects. Urine volumes did not Ruthven & Caesar (1967) remarked on the possible effect of pH of the urine on catecholamine excretion. differ during acid and alkaline regimens nor was there Very recently Reynolds, Ceasar, Ruthven & Sandler a correlation between the two volumes nor between (1978) found a weak, non-significant negative pH and volume. correlation between urinary pH and adrenaline. Our study has also examined the subject in some detail. Catecholamines Six subjects, three men and three women, took part in this experiment. Their mean age was 28.2 + 6.2 Neither mean catecholamine excretion differed years (range 23-40) and all were paramedical significantly with the changes in urinary pH. However, Table 1 Mean ± s.d. of urinary pH, volume and catecholamine excretion in acid and alkaline urine
pH
Volume (ml)
Acid
Alkaline
t. paired value 5df
Significance
Correlation
Significance
5.78 + 0.32
7.44 + 0.54
17.1
LETTERS TO THE EDITORS
311
EFFECT OF URINARY,pH AND FLOW RATE ON CATECHOLAMINE EXCRETION Despite intensive investigations of factors influencing personnel. Ammonium chloride (0.1 g kg-' body urinary excretion of catecholamines, the effect of weight day-') and potassium citrate (8-10 g daily) urinary pH and urinary flow rate has been relatively were used for urinary acidification and alkalinization neglected. The urinary excretion of weakly acidic and respectively. Half received ammonium chloride basic drugs and of a number of endogenous followed I week later by the citrate, the other three compounds and monoamines is pH-dependent (Price received the drugs in reverse order. Two hour urinary 1975, 1976; Weiner & Mudge, 1964). specimens were collected daily for the 5 week days. In an analysis of the effect of pH on the biological The subjects emptied their bladders at 12.00 h then activity of the catecholamines in vivo, Lewis (1954) voided again in an acid-washed container at 14.00 h. observed that sympathomimetic amines are strong The subjects started taking the salt on Monday bases of pK, (amino) 9.4-10.8 and weak acids of pK, morning in divided specified dose (6 hourly) until the (phenolic) 8.8-9.5, that ionization does not account pH changes had reached 5-or 8 respectively. When for the difference in activity of these and that at this pH was attained the subject stopped the medicaphysiological pH the compounds exist almost wholly tion but continued to provide specimens for the rest of as cations (base). Lewis' (1954) measurements were the week. made at 20°C and values at 370C are slightly higher The urinary volume was measured and the pH (Armstrong & Barlow, 1976). Two factors further recorded using a pH meter. The catecholamines were complicate the pH effect on the activity of amines. assayed using a spectrofluorophotometric method First, pK, changes with the concentration of the (Carruthers, Taggart, Conway, Bates & Somerville, solution, decreasing with dilution of the amines. 1970). The limit of detection is 0.5 ng/ml for both Secondly, the amines tend to form zwitterions, with amines. negative and positive ions present simultaneously. But the chemical features which favour zwitterion pH and volume formation do not favour activity at a-adrenoceptors, nor is there a correlation with activity at /The mean urinary pH on the acid regimen differed adrenoceptors (Armstrong & Barlow, 1976). significantly from that on the alkaline (Table 1). Thus Some studies have touched on catecholamines. Levi the administration of potassium citrate and (1972) stated that Finholt & Stokke (1952) found that ammonium chloride had some effect, with a mean when urine becomes alkaline e.g., after hyperventiladifference of 1.66 units between pH values of the tion, catecholamine oxidation in the urine is subjects' two samples. There is also a significant but low positive correlation between the acid and alkaline accelerated. Townsend & Smith (1973) and Sandler, pH values for the subjects. Urine volumes did not Ruthven & Caesar (1967) remarked on the possible effect of pH of the urine on catecholamine excretion. differ during acid and alkaline regimens nor was there Very recently Reynolds, Ceasar, Ruthven & Sandler a correlation between the two volumes nor between (1978) found a weak, non-significant negative pH and volume. correlation between urinary pH and adrenaline. Our study has also examined the subject in some detail. Catecholamines Six subjects, three men and three women, took part in this experiment. Their mean age was 28.2 + 6.2 Neither mean catecholamine excretion differed years (range 23-40) and all were paramedical significantly with the changes in urinary pH. However, Table 1 Mean ± s.d. of urinary pH, volume and catecholamine excretion in acid and alkaline urine
pH
Volume (ml)
Acid
Alkaline
t. paired value 5df
Significance
Correlation
Significance
5.78 + 0.32
7.44 + 0.54
17.1
