- Email: [email protected]
Pharmacokinetics of diminazene in female boran (bos indicus) cattle
e excretion before and 15 days after Liv.52 treatment (ug. Mean + SE). O-3 Hour 518.37 f 73.01 1455.83 * f 196.33
Mamman
3-6 Hour 198.41 f 22.39 1057.83 * It 89.82
*, M., Aliu * *, Y -0. and Peregrine * , A.S.
* International Laboratory for Research on Animal Diseases, P.O. Box 30709, Nairobi, Kenya und ** Dept. of Veterinary Physiology and Pharmacology, Ahmadu Bell0 University, Zaria, Nigeria Diminazene aceturate (BeredR) or Gana~eg(~) is probably the most widely used therapeutic agent for trypanosome infections of domestic livestock in sub-Saharan Africa. The disposition and absorption kinetics of diminazene were studied in five healthy, 11-14 month old, female Boran ( BOS ~~Z&CUS) cattle. Single doses (3.5 mg kg-‘) of diminazene, as the diaceturate salt, were injected intravenously (IV) and intramuscularly (IM) in a single cross-over design with a 6-week wash-out period. Following paired-ion extraction, high-performance liquid chromatography (Aliu and Odegaard, 1983) was used to determine the concentration of intact diminazene in plasma, whole blood and urine samples collected prior to, and at various time intervals after each drug administration. The disposition kinetics relating to both the IV and IM administration experiments, as analysed i ,y nonlinear least squares regression, were best described by a three-compartment open model. Following the IV bolus injection, plasma diminazene concentrations rapidly declined from 10.16 f 2.02 ug ml- * at 5 minutes to 2.34&-0.40 ug ml-’ at 1 hour and 0.47f0.10 ug ml-’ at 48 hours. In three animals, plasma levels of 0.05 + 0.02 ug ml-l were detected at 4 weeks. However, the drug was not detected in plasma from any of the five animals at 6 weeks. One of the characteristics of the IM dose was rapid absorption; the absorption half-life was 8.6 f 4.2 minutes. The C 3.71 f 0.56 ug ml- *, was attained in 10-15 minutes and a systemic availability of 100.0 f 2.0% was estimated. NT&h the plasma concentrations at 1 hour (2.21 f 0.26 ug ml-‘) and at 48 hours (0.52 f 0.06 ug ml-‘) were not significantly different from those present at the same time intervals after IV administration, 0.13 ug ml-’ was detected up to, but not beyond, 10 weeks in three animals following the IM dose. About 8.3 f 0.8% of the IM dose was excreted intact in the urine within 24 hours. In studies with stocks of Tlypancsomu brucei brucei, Kaminsky et al. (1989) demonstrated that the 24hour in oitro effective concentration (EC,) for one set of stocks was 0.018-0.058 ug ml-’ diminazene aceturate, but was 1.29-2.37 ug ml-’ for another group of stocks. However, both sets of stocks died out when incubated for 2-4 days in the presence of 0.1 ug ml- ’ diminazene aceturate. On the basis of the kinetic parameters obtained, 2 IM doses of diminazene aceturate at 7.0 mg kg-‘, administered 48 hours apart, will maintain the plasma diminazene concentration in excess of 0.5 ug ml-’ for 4 days. If the aforementioned stocks, examined irl oitro, represent the spectrum of resistance found in the field, this therapeutic regime would appear to be adequate to cure diminazene-sensitive and diminazene-resistant trypanosome infections in domestic livestock.
Aliu, Y-0. and CMegaard, S., 1983, J. Chromatogr. 276, 218-223. Raminsky, R, Chuma, F. and Zweygarth, E., 1989, Exp. Pan&t., 69, 281-289.
Mamman
3-6 Hour 198.41 f 22.39 1057.83 * It 89.82
*, M., Aliu * *, Y -0. and Peregrine * , A.S.
* International Laboratory for Research on Animal Diseases, P.O. Box 30709, Nairobi, Kenya und ** Dept. of Veterinary Physiology and Pharmacology, Ahmadu Bell0 University, Zaria, Nigeria Diminazene aceturate (BeredR) or Gana~eg(~) is probably the most widely used therapeutic agent for trypanosome infections of domestic livestock in sub-Saharan Africa. The disposition and absorption kinetics of diminazene were studied in five healthy, 11-14 month old, female Boran ( BOS ~~Z&CUS) cattle. Single doses (3.5 mg kg-‘) of diminazene, as the diaceturate salt, were injected intravenously (IV) and intramuscularly (IM) in a single cross-over design with a 6-week wash-out period. Following paired-ion extraction, high-performance liquid chromatography (Aliu and Odegaard, 1983) was used to determine the concentration of intact diminazene in plasma, whole blood and urine samples collected prior to, and at various time intervals after each drug administration. The disposition kinetics relating to both the IV and IM administration experiments, as analysed i ,y nonlinear least squares regression, were best described by a three-compartment open model. Following the IV bolus injection, plasma diminazene concentrations rapidly declined from 10.16 f 2.02 ug ml- * at 5 minutes to 2.34&-0.40 ug ml-’ at 1 hour and 0.47f0.10 ug ml-’ at 48 hours. In three animals, plasma levels of 0.05 + 0.02 ug ml-l were detected at 4 weeks. However, the drug was not detected in plasma from any of the five animals at 6 weeks. One of the characteristics of the IM dose was rapid absorption; the absorption half-life was 8.6 f 4.2 minutes. The C 3.71 f 0.56 ug ml- *, was attained in 10-15 minutes and a systemic availability of 100.0 f 2.0% was estimated. NT&h the plasma concentrations at 1 hour (2.21 f 0.26 ug ml-‘) and at 48 hours (0.52 f 0.06 ug ml-‘) were not significantly different from those present at the same time intervals after IV administration, 0.13 ug ml-’ was detected up to, but not beyond, 10 weeks in three animals following the IM dose. About 8.3 f 0.8% of the IM dose was excreted intact in the urine within 24 hours. In studies with stocks of Tlypancsomu brucei brucei, Kaminsky et al. (1989) demonstrated that the 24hour in oitro effective concentration (EC,) for one set of stocks was 0.018-0.058 ug ml-’ diminazene aceturate, but was 1.29-2.37 ug ml-’ for another group of stocks. However, both sets of stocks died out when incubated for 2-4 days in the presence of 0.1 ug ml- ’ diminazene aceturate. On the basis of the kinetic parameters obtained, 2 IM doses of diminazene aceturate at 7.0 mg kg-‘, administered 48 hours apart, will maintain the plasma diminazene concentration in excess of 0.5 ug ml-’ for 4 days. If the aforementioned stocks, examined irl oitro, represent the spectrum of resistance found in the field, this therapeutic regime would appear to be adequate to cure diminazene-sensitive and diminazene-resistant trypanosome infections in domestic livestock.
Aliu, Y-0. and CMegaard, S., 1983, J. Chromatogr. 276, 218-223. Raminsky, R, Chuma, F. and Zweygarth, E., 1989, Exp. Pan&t., 69, 281-289.