The potency of single doses of a new aldosterone antagonist, prorenoate, in reversing the renal effects of the synthetic mineralocorticoid fludrocortisone was compared to that of spironolactone in a double-blind balanced crossover study in 12 healthy subjects. The potency of prorenoate potassium as related to elevation of the urinary log 10 10 Na/K ratio (2.69:1) and as related to potassium retention (3.75:1) was significantly higher than that of spironolactone. Prorenoate produced greater natriuresis (1.64:1) but the difference was not significant. There was evidence for a qualitative difference between spironolactone and prorenoate; the latter significantly more potent in retaining potassium than in increasing sodium excretion. The simple methodology described is based on standard bioassay principles, yielded a valid and sensitive comparison of the two drugs, and should prove useful in the evaluation of other aldosterone antagonists.

The pharmacological activity of single doses of the two aldosterone antagonists, potassium canrenoate and spironolactone, was examined in two studies in healthy volunteers. Both drugs were active in reversing urinary electrolyte changes induced by fludrocortisone in periods 2 to 16 hr after treatment. Potassium canrenoate was significantly less potent that spironolactone on a weight or molar basis, with best estimates of the relative potency potassium canrenoate: spironolactone of approximately 0.3:1. On a weight basis the two drugs yielded plasma levels of the metabolite canrenone which were approximately equivalent. The results indicate that canrenone is not the principal pharmacologically active metabolite of spironolactone. Our study suggests that a major part of the renal antimineralocorticoid activity of spironolactone may be attributable to minor sulfur-containing metabolites or their precursors having a high renal clearance that affords access to their site of activity via the renal tubular fluid.

Relative dose ratios of the mineralocorticoid antagonists spironolactone (100 mg and 200 mg daily) and canrenoate-K (200 mg daily) at steady state were defined in six healthy subjects with fludrecortisone as the mineralocorticoid agonist. The urine log 10 Na/K responses during spironolactone treatments were consistent with the law of mass action. The potency of canrenoate-K was 0.68 (95% C.L. 0.53 to 0.89) that of spironolactone on a weight basis. Approximately 72% of the renal antimineralocorticoid activity of spironolactone could attributed to the metabolite canrenone. The results at steady state are contrasted with those of a previously study comparing single doses of spironolactone and canrenoate-K.

I Log dose-responses for the loop d *etics bumetanide and frusemide in healthy subjects deviated significantly from parallelism as reg ds urine volume and sodium excretion. Ignoring the nonparallelism the best estimate of natriuretic potency (bumetanide: frusemide) was 46: 1 in the bumetanide dose range 0.5-2 mg. 2 For a given natriuresis the urinary potassium excretion following bumetanide was significantly lower than that for frusemide within this dose range. 3 The data illustrate the limitations of studies comparing diuretics at a single dose level. Extrapolation of the observed log dose-response curves provides one possible explanation for the relative potency (bumetanide: frusemide) of 20: 1 reported when the drugs are used at high dosage in patients with renal failure.

BackgroundDengue is an arboviral infection classically presenting with fever, arthralgia, headache, and rashes. It is hyperendemic in Sri Lanka and has a major impact on health. Neurological complications of dengue fever are rare but have been reported in the literature.Case presentationA 60-year-old Sri Lankan man presented with a history of fever, arthralgia, and generalized malaise of 2 days duration. A diagnosis of dengue was confirmed with leukopenia, thrombocytopenia, and positive NS1 antigen done on day 2 without evidence of hemoconcentration. On admission, our patient had weakness of the bilateral lower limbs, which progressed in an ascending pattern involving both upper limbs and neck muscles, requiring assisted ventilation. Electromyography confirmed a demyelinating polyneuropathy and cerebrospinal fluid showed albumincytological dissociation. He was treated with intravenous immunoglobulins and made an uneventful recovery. Subsequently, his immunoglobulin M test result for dengue virus was positive.ConclusionsGuillain-Barré syndrome is a rare but possible neurological sequel following dengue fever. In regions where dengue is hyperendemic, screening for dengue illness may be important in patients presenting with acute flaccid paralysis.

normal English and German sUbjectsA major problem in quantitating dosage equivalence of diuretics is the variation in response between subjects in normal populations as well as in patients with edema. There are also wide variations in response within subjects. Some of this variation can be explained by measurement of factors present prior to drug administration. Known examples are the correlation between the aldosterone secretion rate before treatment and the diuretic response to ethacrynic acid,5 the correlation Supported by Hoechst Phannaceuticals, England.

The bioavailability and pharmacologic activity of tablets containing micronized spironolactone chemical (median particle size 2.21 micrometers) were compared to those of tablets made from standard spironolactone chemical (median particle size 78.8 micrometers) in healthy men. Apart from particle size, all features of these tablets were identical. After 200-mg single doses, the bioavailability of micronized tablets was significantly higher than that of standard tablets. Furthermore, as assessed by 24-hour urine log10 10 Na/K ratio, the pharmacologic activity of micronized spironolactone was significantly greater than that of the standard formulation. The significant influence on renal antimineralocorticoid activity of raised plasma and urinary levels of canrenone, quantitatively the major active metabolite of spironolactone in man, emphasizes the clinical importance of the bioavailability of spironolactone preparations. Since this study, the process used in the manufacture of spironolactone (Aldactone) tablets has been under review.

Latex, hydrophilic polymer-coated latex and PVC balloon indwelling urethral catheters were compared in respect of the urinary tract infections arising in association with their use in male patients. The polymer (Hydron) coating conferred no benefit over uncoated latex which in turn was indistinguishable from PVC. No significant differences in the spectra of infecting organismns were observed between the 3 catheter types.