Abstract
Cotyledoside, a bufadienolide cardiac glycoside, was administered intravenously to sheep in 2 studies. In experiment 1, sheep (n = 4) received 0.0135 mg/kg daily on 5 consecutive days and in the 2nd experiment, sheep (n = 4) received 0.027 mg/kg as a single dose. Jugular blood was collected at different time intervals and kinetic parameters were determined. The data fitted a 1-compartmental model. In both experiments a short half-life (t1/2) and mean residence time (MRT), a relative small volume of distribution (Vd(ss)) and rapid clearance were calculated. In the 1st experiment, t1/2 and MRT increased significantly (P < 0.007) from Day (D) 0 to D4. It is suggested that the rapid decline in plasma cotyledoside concentrations in sheep denotes rapid distribution of cotyledoside to the tissues or extracellular spaces and possible accumulation at the biophase.
Highlights
Krimpsiekte, a chronic form of cardiac glycoside poisoning, manifests as a paretic syndrome and occurs predominantly in small stock[5,6]
D 0 and D 4 of the 1st experiment and following a single intravenous administration in the 2nd experiment are tabulated in Tables 1 and 2
Semilogarithmic plots of plasma cotyledoside concentration versus time are presented in Figs 1 and 2
Summary
Krimpsiekte, a chronic form of cardiac glycoside poisoning, manifests as a paretic syndrome and occurs predominantly in small stock[5,6]. Naudé and Schultz[8] coined the term ‘cumulative bufadienolides’ following the successful demonstration of a cumulative effect with cotyledoside isolated from Tylecodon wallichii. These authors determined a subcutaneous LD50 of 0.116 mg/kg cotyledoside in guinea pigs and injected others subcutaneously with 25 % and 50 % of the subcutaneous LD50 per day until they died. No clinical signs appeared before the LD50 was reached and marked nervous signs occurred when 5 × 25 % or 3 × 50 % the LD50 were administered[8]
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