| dc.description.abstract | The successes achieved with oxytetracycline (O'TC) and its relatively cheaper cost
in the treatment and prophylaxis of Ehrlichia canis (E. canis) infection makes it an
important drug in Kenya where the disease is widespread. Long-acting
formulations of O'TC given together with anti-inflammatory drugs have been
reported to be suitable for use in dogs in the treatment of ehrlichiosis. The primary
purpose of the long-acting formulation is to provide, with a single injection, plasma
O'TC concentrations and clinical efficacy equivalent to those achieved with two or
three daily injections of short-acting conventional products. This study was carried
out to investigate the effect of experimental canine ehrlichiosis on the serum
concentrations and pharmacokinetic parameters of a long-acting O'TC formulation
in dogs following intramuscular injection of single doses (20 mg/kg body weight).
In addition, the clinical efficacy of the long-acting O'TC formulation in E.canis
infection and the possible effects of splenectomy on pharmacokinetics of O'TC
were also studied.
Nine adult mongrel dogs of both sexes were used in the study. They were
randomly divided into two groups, group 1 (n=S) and group 2 (n=4). In the first,
experiment, five dogs (group 1) were used to study the effect of experimentally
induced E. canis infection on the pharmacokinetics of O'TC (Terramycin LA,
pfizer Labs Ltd. New. -Y.ork USA) administered intramuscularly.
The study was conducted in two consecutive trials in a cross over design separated
by a wash-out period of six weeks. Blood samples of 5 ml each were collected
from the jugular vein using 5 ml and gauge 19 disposable syringes and needles
respectively at 0 (pretreatment), 0.25, 0.5, 1, 2, 4, 8, 12, 24, 36, 48, 72, 84 and 96
hours interval following intramuscular administration of OTC at the recommended
dosage rate of 20 mg/kg, before infection, and at the onset of fever twenty days
after infection. Serum concentrations of OTC were determined by a quantitative
microbiological assay using an agar-gel diffusion method employing Bacillus
cereus var mycoides (ATCC 11778) as the test organism with a limit of detection
of approximately 0.1 uglml.
In the second experiment, four dogs (group 2) were splenectomized and infected
with E.canis three weeks later. At the onset of fever twelve days after infection, the dogs were treated with OTC like in group 1 dogs. Blood samples were collected and serum concentrations assayed in a similar manner to that described for group 1 dogs, to investigate the effect of splenectomy on the pharmacokinetics of O'TC. Clinical signs and haematological parameters were monitored in both groups of dogs following the challenge and after treatment with the long-acting OTC fomulation. In addition, peripheral blood smears were taken once per week from all the dogs to examine for E. canis. Following infection, dogs developed varied signs of canine ehrlichiosis. These signs included: pyrexia, anorexia, loss of body condition, depression, pale and congested conjuctival mucus membrane.
The clinical signs developed by day eighteen and ten post-infection in
non-splenectomized and splenectomized dogs respectively. E.canis was re-isolated
from three of the nine dogs (33.3%) four weeks after treatment with the long acting
O'TC. Packed cell volumes were significantly decreased (p < 0.05) in both group I and group 2 dogs following infection. The platelet counts were apparently decreased (p > 0.05) while the corresponding mean platelet volumes were apparently increased in both groups of dogs following infection. Serum creatinine and alkaline phosphatase were significantly increased (p < 0.05) in both groups following infection.
The serum concentration-time curve of O'TC after intramuscular injection before
. infection in group 1, was best described by a two-compartment open model with
first order absorption. However, after experimental infection, it was best described
by a one-compartment open model in both group 1 and group 2. The maximum
serum concentrations (em.x) of O'TC in non-splenectomized (group 1) and
splenectomized (group 2) dogs (2.49 ± 0.14 and 2.38 ± 0.12 ug/ml, respectively)
after infection were significantly (p < 0.05) lower than 4.39 ± 0.20 ug/ml in healthy
dogs, suggesting an increased distribution volume of the peripheral compartment.
The corresponding times taken to attain these concentrations (tmax)in group 1 and
group 2 dogs (0.48':1..0.06 and 0.57 ± 0.12 h, respectively) after infection, were
significantly shorter (p < 0.01) than 2.13. ± 0.16 h in healthy dogs.
The elimination half-lives (tll2Jl)in group 1 and group 2 dogs (23.09 ± 3.13 and
25.4 ± 2.34 h, respectively) after infection were significantly increased (p<O.Ol)
while the corresponding rate constants (13),(0.033 ± 0.01 and 0.028 ± 0.005 hot,
respectively) significantly decreased (p < 0.05). The absorption half-lives (t1l2ab)in
non-splenectomized and splenectomized dogs after infection (0.19 ± 0.07 and
0.088 ± 0.03 h, respectively) were significantly decreased (p < 0.05). The volumes
of distribution at steady state, (Ve«) in both group 1 and group 2 dogs after
infection (15.67 ± 4.97 and 18.25 ± 0.92 Llkg, respectively) significantly increased
(p < 0.01), suggesting low serum concentrations in the disease state.
This study indicates that experimental ehrlichiosis had an effect on the
pharmacokinetics of O'I'C in both non-splenectomized and splenectomized dogs.
Long-acting oxytetracycline formulation can be used as an alternative drug in
E.canis infection when given as two injections 36 h apart. Splenectomy was found
to have no effect on the pharmacokinetics parameters of oxytetracycline in both
non-splenectomized and splenectomized dogs infected with E canis | en |
| dc.description.department | a
Department of Psychiatry, University of Nairobi, ; bDepartment of Mental Health, School of Medicine,
Moi University, Eldoret, Kenya | |
