Objective—To validate use of high-performance liquid
chromatography (HPLC) in determining
imipramine concentrations in equine serum and to
determine pharmacokinetics of imipramine in narcoleptic
Animals—5 horses with adult-onset narcolepsy.
Procedure—Blood samples were collected before
(time 0) and 3, 5, 10, 15, 20, 30, and 45 minutes and
1, 2, 3, 4, 6, 8, 12, and 24 hours after IV administration
of imipramine hydrochloride (2 or 4 mg/kg of body
weight). Serum was analyzed, using HPLC, to determine
imipramine concentration. The serum concentration-versus-time curve for each horse was analyzed
separately to estimate pharmacokinetic values.
Results—Adverse effects (muscle fasciculations,
tachycardia, hyperresponsiveness to sound, and
hemolysis) were detected in most horses when
serum imipramine concentrations were high, and
these effects were most severe in horses receiving 4
mg of imipramine/kg. Residual adverse effects were
not apparent. Value (mean ± SD) for area under the
curve was 3.9 ± 0.7 h × μg/ml, whereas volume of
distribution was 584 ± 161.7 ml/kg, total body clearance
was 522 ± 102 ml/kg/h, and mean residence
time was 1.8 ± 0.6 hours. One horse had signs of narcolepsy
6 and 12 hours after imipramine administration;
corrresponding serum imipramine concentrations
were less than the therapeutic range.
Conclusions and Clinical Relevance—Potentially
serious adverse effects may be seen in horses administered
doses of imipramine that exceed a dosage of
2 mg/kg. Total body clearance of imipramine in horses
is slower than that in humans; thus, the interval
between subsequent doses should be longer in horses.
(Am J Vet Res 2001;62:783–786)