Effects of an oral vasopressin receptor antagonist (OPC-31260) in a dog with syndrome of inappropriate secretion of antidiuretic hormone

Objective The syndrome of inappropriate secretion of antidiuretic hormone i s a rare disorder in dogs characterised by hypo-osmolality and persistent a rginine vasopressin production in the absence of hypovolaemia and/or hypote nsion. The study describes the efficacy and safety of the nonpeptide select ive arginine vasopressin V-2 receptor antagonist OPC-31260 in a dog with th e naturally occurring syndrome. Design The detailed case history of a dog with spontaneous syndrome of inap propriate secretion of antidiuretic hormone that received long-term therapy with oral OPC-31260 is presented. Effects of the first dose of OPC-31260 a nd of a dose administered after a continuous dosing period of 12 days are r eported. Procedure Packed cell volume, plasma sodium, total protein, arginine vasopr essin, renin activity, atrial natriuretic peptide, urine specific gravity, urine output, heart rate and body weight were monitored for 2 h before, and for 4 h after, the first dose of OPC-31260. The same parameters plus plasm a osmolality and urine osmolality were monitored when an identical dose was administered after 12 days of therapy. Results Oral administration of OPC-31260 at 3 mg/kg body weight resulted in marked aquaresis with increased urine output and decline in urine specific gravity within 1 h. Corresponding increases in concentrations of plasma so dium, plasma osmolality and plasma renin activity were recorded over a 4 h period. Arginine vasopressin concentration remained inappropriately elevate d throughout the study. Results were similar when the trial procedure was r epeated after a stabilisation period of 12 days. Long-term therapy with OPC -31260 at a dose of 3 mg/kg body weight orally every 12 h resulted in good control of clinical signs with no deleterious effects detected during a 3-y ear follow-up period. Despite sustained clinical benefits observed in this case, plasma sodium did not normalise with continued administration of the drug. Conclusions Treatment of a dog with naturally occurring syndrome of inappro priate secretion of antidiuretic hormone with OPC-31260 at 3 mg/kg body wei ght orally every 12 h resulted in marked aquaresis and significant palliati on of clinical signs with no discernible side-effects detected over a 3-yea r period. Thus, OPC-31260 appears to offer a feasible medical alternative t o water restriction for treatment of dogs with syndrome of inappropriate se cretion of antidiuretic hormone. Higher doses of OPC-31260 may be required to achieve and maintain normal plasma sodium in dogs with this syndrome.