Indacrinone: Modification of diuretic, uricosuric, and kaliuretic actions by amiloride

The response to indacrinone, a new indanone diuretic, was studied in 12 healthy subjects. Ten milligrams alone and in combination with either 2.5 mg or 5 mg amiloride was given in a randomized double‐blind study with placebo control to study its action and to assess the optimum combination. Indacrinone alone induced an increase in urine flow rate and in sodium, potassium, and hydrogen ion excretion for at least 8 hr. Indacrinone also induced an initial uricosuria in the first 4 hr, followed by urate retention in the subsequent 12 to 24 hr, with no resultant change in the mean 24‐hr urate excretion and minimal changes in the serum urate concentrations. The addition of 2.5 mg amiloride to the 10 mg indacrinone lowered potassium excretion to control levels, whereas addition of 5 mg amiloride resulted in net retention of potassium. With both doses of amiloride, the increased free hydrogen ion excretion after indacrinone returned to placebo levels. There were minor increases in serum creatinine, consistent with volume depletion due to the diuresis. There was a reduction in urinary calcium excretion. Our study shows that the combination of 10 mg indacrinone and 2.5 mg amiloride induces useful diuresis with minimal overall effect on urate, potassium, and hydrogen ion excretion. Clinical Pharmacology and Therapeutics (1980) 28, 45–51; doi

Induction of hepatic cytochrome P-450 1A in Pikey Bream (Acanthopagrus berda) collected from agricultural and urban catchments in far north Queensland

A variety of sources of organic contaminants to the Great Barrier Reef lagoon and near-shore environment exist including boating activity, agriculture and urban run-off. Cytochrome P-450 1A activity as measured by ethoxy-resorufin O-deethylase (EROD) activity has been widely used as an indicator of the exposure of fish to organic contaminants such as polychlorinated biphenyls (PCB), polycyclic aromatic hydrocarbons (PAH) and some organochlorine pesticides. This study demonstrates the successful application of EROD measurements in a common Australian tropical estuarine fish species, Acanthopagrus berda (Pikey Bream), to identify areas under potential stress from organic contaminants. Fish were captured from four creeks draining agricultural land, a creek draining urban land and two creeks with less disturbed catchments. Significant induction of cytochrome P450-1A was observed in fish captured from Ross Creek (urban catchment, 7.4-fold) and Cromarty Creek (agricultural catchment, 6.4-fold). Increased activity was also observed in fish captured from other creeks draining agricultural land (Plantation Creek, Victoria Creek, Seymour River, 1.9–2.6-fold) as compared to those captured from creeks in undisturbed catchments (Baldy Creek, Fisher Creek, 67–114 pmol/min/mg protein)