No abstract

The pharmacokinetics of dantrolene sodium were investigated in horses following both intravenous (2 mg/kg) and intragastric (4 mg/kg) administration. Two ponies also received dantrolene sodium intravenously (2 mg/kg) in a pilot study to obtain preliminary kinetic data and to determine urinary and biliary excretion of the intact drug. Distribution and elimination of dantrolene was rapid, resulting in an elimination half-life of 129 +/- 8 (SEM) min and a whole body clearance of 4.16 +/- 0.52 ml/min/kg. Following intragastric administration, dantrolene rapidly acheived peak concentrations within 1.5 h, but was incompletely absorbed, with a bioavailability of 39 +/- 10%. Small amounts of intact drug were recovered in urine and bile. Based upon disposition kinetics of dantrolene in these studies, intravenous and intragastric dosage regimens were determined which would maintain blood dantrolene concentrations within the predicted clinically effective range.

The standard drug Stelazine (STEL), at a dose of 50 mg/day, exhibited therapeutic activity significantly different from placebo (PL) activity on several variables, most notably BPRS, attesting to the sensitivity of the experiment. On the other hand, the investigational drug, loxapine (LOX), in doses of 100 mg/day for four weeks, could be differentiated from PL as treatment in the described population on only one variable (NGI-Imp.) and one item of the BPRS. On several variables, positive trends were noted, but the differences from PL did not attain the critical values necessary for statistical significance at P smaller than 0.05. One might speculate that the relatively short duration of treatment in this study might account for the difference between these disappointing results and the more gratifying results of a previous loxapine study in chronic long-term institutionalized schizophrenics with the same oral dose.