Comparative pharmacokinetics of diminazene in plasma, cerebrospinal fluid and lymph of goats
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A study was undertaken to compare the absorption and distribution of the antitrypanosomal drug diminazene aceturate in plasma, cerebrospinal fluid (CSF) and lymph of goats. The study comprised three groups of three goats each. Animals in each group were treated with a single intramuscular dose of 3.5 mg diminazene base/kg body weight. Thereafter, samples of jugular blood were obtained from animals in the first group at 22 different time intervals within the first 48 h of drug administration. Over the same time intervals, samples of lumbar CSF and prescapular lymph were also obtained through cannulae, placed surgically in animals constituting the second and third groups respectively. Sequentially, diminazene in plasma, CSF and lymph was extracted by an ion-pair technique, and quantified by reverse-phase high-performance liquid chromatography. The concentration-versus-time data obtained were then analysed by standard non-compartmental procedures. In general, concentrations of diminazene in plasma were 2-3 times higher than in lymph and CSF. The observed maximum concentration (Cmax) of diminazene in plasma, 4.53 +-0.41 g/ml, was significantly higher than in the CSF, 0.96+-0.59 g/ml, lymph, 1.21 +-0.58 g/ml. In addition, the occurrence of Cmax in plasma, at 0.44+-0.10 h, was earlier compared to 1.33+-0.58 h in CSF, and 1.11+-0.77 h in lymph. Total body clearance of diminazene determined for the plasma, 0.69+-0.11 ml/min/kg, was significantly greater than in the CSF, 0.23+-0.10 ml/min/kg, and lymph, 0.13+-0.11 ml/min/kg. Consequently, the mean residence time of the drug determined for the plasma, 57.27+-16.49 h, was shorter than in the CSF, 892.72+-12.34 h, and lymph, 2432+-3080.39 h. These findings suggest that although diminazene attains significantly higher levels in the plasma than in the CSF and lymph, it persists longer in the CSF and lymph than in plasma.
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