Further Notes on the Interaction of Spironolactone and Deoxycorticosterone Acetate in Dogs

Kagawa, C. M.; Bouska, D. J.; Anderson, Margaret

doi:10.1530/acta.0.0450079

Cited by 7 publications

(2 citation statements)

References 0 publications

Supporting

Mentioning

Contrasting

Order By: Relevance

“…These authors found that in man the acute kaliuretic action of aldosterone was not sufficiently constant as to allow a clear assessment of the blocking action of spironolactone upon the renal handling of potassium. More recently Kagawa, Bouska, and Anderson (1964) found that the administration of spironolactoneinhibited the effect of 1 1-de-oxycorticosterone on the renal handling of potassium. This blockade was complete.…”

Section: Discussionmentioning

confidence: 99%

Blocking by spironolactone (SC 9420) of the action of aldosterone upon the intestinal transport of potassium, sodium, and water.

Elmslie¹,

Mulholland²,

Shields³

1966

Gut

View full text Add to dashboard Cite

CardiffEDITORIAL COMMENT This study continues the work described in the previous paper and brings out another common factor concerning electrolyte transport.The action of the adrenal mineralocorticoids upon the intestinal mucosa closely resembles their effect upon the renal tubular epithelium (Shields, 1964). Thus, in both organs, the transfer of potassium into the lumen is stimulated by the intravenous administration of aldosterone (Barger, Berlin, and Tulenko, 1958;Shields, Mulholland, and Elmslie, 1966). Because the renal action of the mineralocorticoids can be blocked by the spironolactones (Bartter, 1960) the effect of these agents upon the intestinal action of aldosterone was investigated. METHODThe movement of potassium, sodium, and water into and out of the lumen of isolated segments of ileum (two dogs) and of colon (three dogs) was measured using the radioactive isotopes of sodium and potassium, and the stable isotope of water, deuterium oxide. Details of the preparation and of the experimental technique are given in the previous paper (Shields et al., 1966). TYPES OF EXPERIMENT In each dog, six types of experiment were performed: I Spironolactone alone One hundred mg. spironolactone SC 9420 (Aldactone, Searle) was given by mouth at 6.00 a.m. At 9.00 a.m. an intravenous infusion of 5 % (w/v) dextrose was set up and continued at a rate of 40 ml. per minute. Absorption tests, each lasting 10 minutes, were performed at 1, 2, 2j, 3i, 4, and 5 hours after the beginning of the dextrose infusion. One such experiment was performed in each dog.2 Spironolactone + aldosterone (high dose) The experimental technique was identical to (1), except that at 9.00 a.m., 250 pg. aldosterone (Aldocorten, Ciba) was injected intravenously and a further 250 ,tg. was added to the dextrose solution and delivered to the dog at a rate of 1 jig. per minute. One experiment of this type was performed on each dog.3 Spironolactone + aldosterone (low dose) The experi-'Present address:

show abstract

Section: Discussionmentioning

confidence: 99%

Blocking by spironolactone (SC 9420) of the action of aldosterone upon the intestinal transport of potassium, sodium, and water.

Elmslie¹,

Mulholland²,

Shields³

1966

Gut

View full text Add to dashboard Cite

show abstract

“…However, because of the similarity in chemical structure, it might be suggested that both drugs are active in this regard. Further, it is of interest to note that aldadiene retains the antimineralcorticoid effects of spironolactone ( 12 ) . …”

Section: Materials and Methods Nonfasted Malementioning

confidence: 99%

Stimulation of Liver Microsomal Drug Metabolism in Male and Female Mice by Spironolactone and Aldadiene

Feller

Gerald

1971

Experimental Biology and Medicine

View full text Add to dashboard Cite

Recent findings in our laboratory (1-3) and others (4, 5) have shown that spironolactone (SPL) stimulates the metabolism of drugs by liver microsomes. Stripp and coworkers ( 5 ) reported differences in the nature of enzyme induction in male and female rats after SPL pretreatment. The present study was initiated to ascertain whether SPL inductive effects occur in both sexes of mice. Aldadiene (SC-9376), a major in vivo metabolite of SPL (6), was included to determine if this A6-dethioacetylated metabolite retains the inductive properties of the parent drug. Materials and Methods, Nonfasted maleand female albino Swiss mice, weighing 20-30 g, were used. Spironolactone and aldadiene (100 mg/kg) or corn oil vehicle were given ip twice daily for 3 consecutive days, in a volume of 1.0 ml/100 g of body weight. Experiments were initiated 24 hr after the last dose.Sleeping time. After the injection of hexobarbital sodium (120 mg/kg, ip), the duration of sleep was determined to be the time interval between the loss and restoration of the righting reflex.Microsomal enzyme assays. Procedures for the isolation of liver microsomes and their incubation with hexobarbital and ethylmorphine were conducted as previously described ( 1). Incubation mixtures contained the following components in a final volume of 3.0 ml: 5 mg of microsomal protein, a NADPHgenerating system (consisting of 2 enzyme units of glucose-6-phosphate dehydrogenase, 1 This work was supported by Grant FR 05607-03, from the National Institutes of Health. A preliminary report appeared in Pharmacologist 12, 2 79 (1970).15 pmoles of glucose-6-phosphate, 1.2 pmdes of NADDP, 150 pmoles of Tris-HC1 buffer, pH 7.4) , and either 15 pmoles of ethylmorphine or 2 pmoles of hexobarbital.The extent of hexobarbital metabolism and ethylmorphine N-demethylation by liver microsomes was assayed using the procedures described by Cooper and Brodie (7) and Nash (8), respectively.Cytochrome P-450 was estimated by the method of Omura and Sat0 (9) ; NADPHcytochrome c reductase was measured by the procedure of Phillips and Langdon (10) and microsomal protein was assayed by the method of Lowry et al. (1 1). Statistical comparisons were made using Student's t test.Results. The influence of spironolactone (SPL) and aldadiene pretreatment on various hepatic microsomal enzyme systems and related parameters in mice is presented in Tables I and 11, respectively. These results reveal that there are no qualitative differences in the induction by either drug in both sexes. It was observed that both SPL and aldadiene increased liver weight ( 1 1-2 7 % ) , liver/body weight ( 14-20%) and microsomal protein content . In addition, the observed reductions in hexobarbital sleeping times (4-18% of the control group) are in agreement with the 2-fold increases noted in the microsoimal metabolism of hexobarbital. Similarly, pretreatment with either drug elevated the N-demethylation of ethylmorphine ( 1.3-2.5-fold) . In the same series of experiments, components of the hepatic microsomal electron transport sy...

show abstract

Pharmacokinetic and Metabolic Fate of Potassium Canrenoate (SC-14266) in Man

Karim¹,

Ranney²,

Maibach

1971

Journal of Pharmaceutical Sciences

View full text Add to dashboard Cite

Further Notes on the Interaction of Spironolactone and Deoxycorticosterone Acetate in Dogs

Cited by 7 publications

References 0 publications

Blocking by spironolactone (SC 9420) of the action of aldosterone upon the intestinal transport of potassium, sodium, and water.

Blocking by spironolactone (SC 9420) of the action of aldosterone upon the intestinal transport of potassium, sodium, and water.

Stimulation of Liver Microsomal Drug Metabolism in Male and Female Mice by Spironolactone and Aldadiene

Pharmacokinetic and Metabolic Fate of Potassium Canrenoate (SC-14266) in Man

Contact Info

Product

Resources

About