Pharmacokinetics and pharmacodynamics of desoxycorticosterone pivalate in dogs with hypoadrenocorticism.

Abstract

BACKGROUND: Desoxycorticosterone pivalate (DOCP) is commonly used to treat mineralocorticoid deficiency in dogs with hypoadrenocorticism (HA). HYPOTHESIS/OBJECTIVE: To determine the pharmacokinetics and pharmacodynamics of DOCP. ANIMALS: Twenty-one dogs with newly diagnosed HA. METHODS: Prospective clinical trial. Dogs were randomly assigned to treatment with an SC injection of either 1.1&#xa0;mg/kg (low-dose) or 2.2&#xa0;mg/kg (label-dose) DOCP. Blood samples were collected at set time points for measurement of serum drug concentrations, serum electrolyte concentrations, and plasma renin activities (PRAs). A one-compartment model was used to determine pharmacokinetics variables. Pharmacodynamics variables including duration of DOCP action and duration of overtreatment were estimated from serum electrolyte concentrations and PRA. Pharmacokinetics and pharmacodynamics variables were compared between low-dose and label-dose groups. RESULTS: Maximum drug concentrations and overall drug exposures were higher in label-dose dogs (1.22&#xa0;&#xb1;&#xa0;0.46&#xa0;ng/mL and 32.1&#xa0;&#xb1;&#xa0;12.3&#xa0;day&#xa0;&#xd7;&#xa0;ng/mL) than in low-dose dogs (0.69&#xa0;&#xb1;&#xa0;0.32&#xa0;ng/mL and 19.6&#xa0;&#xb1;&#xa0;5.3&#xa0;day&#xa0;&#xd7;&#xa0;ng/mL; P&#xa0;=&#xa0;.008 for both comparisons). However, duration of DOCP action as determined by PRA in label-dose (55&#xa0;&#xb1;&#xa0;16&#xa0;days) and low-dose (45&#xa0;&#xb1;&#xa0;12&#xa0;days) dogs was not different (P&#xa0;=&#xa0;.2). Serum electrolyte concentrations overestimated the duration of action in the combined group by a mean of 10&#xa0;days when compared with PRA (P&#xa0;<&#xa0;.001). CONCLUSIONS AND CLINICAL IMPORTANCE: Pharmacokinetics and pharmacodynamics data suggest that low-dose DOCP administered every 5-7&#xa0;weeks is a reasonable treatment strategy for most dogs with HA. Prolonging dosing intervals >&#x2009;7-8&#xa0;weeks based solely on electrolyte concentrations should be avoided.