Eric S. Mitema

Oxytetracycline residue levels in chicken eggs after oral administration of medicated drinking water to laying chickens

Twenty laying birds were divided into four groups (n = 5) and given drinking water containing 0, 400, 600, and 800 mg/l of oxytetracycline respectively for 7 days. Eggs were collected continuously for 17 days after drug administration and stored at +4 degrees C. The oxytetracycline residues in yolk and albumen were analysed using a microbiological method with Bacillus cereus var. mycoides ATCC 11778 as the test organism. The mean maximum concentration of oxytetracycline was observed 2 days earlier in the albumen than in the yolk. The mean values in yolk and albumen were 0.526 and 0.280 mg/kg respectively. The depletion period was shorter for albumen than for yolk and oxytetracycline was detected in the yolk and albumen up to days 13 and 10 respectively. Withdrawal periods depended on the concentration of the antibiotic administered. Oxytetracycline residues reached a peak faster in albumen than in yolk, although the residues persisted for longer periods in the yolk.

Comparative efficacy of pyrethrum marc with albendazole against sheep gastrointestinal nematodes

The efficacies of pyrethrum marc and of albendazole against experimental sheep gastrointestinal nematode infection were compared. Sheep were infected orally with 10000 larvae (Haemonchus spp. (60.1%), Oesophagostomum spp. (13.9%), Trichostrongylus spp. (13.2%), Cooperia spp. (8.3%), Nematodirus spp. (3.5%), Strongyloides spp. (0.8%) and Ostertagia spp. (0.2%)). Faecal egg count reduction in albendazole-treated sheep was 100% by day 4 following treatment, compared to 37.03%, 31.3%, 38.9% and 51.8% on days 4, 6, 8 and 10 in pyrethrum marc-treated sheep. These reductions were statistically significant on days 8 and 10 post-treatment (p<0.05). The potential for using pyrethrins for helminth treatment is discussed.

Aspects of the Pharmacokinetics of Doxycycline Given to Healthy and Pneumonic East African Dwarf Goats by Intramuscular Injection

Ole-Mapenay, I.M., Mitema, E.S. and Maitho, T.E., 1997. Aspects of the pharmacokinetics of doxycycline given to healthy and pneumonic East African dwarf goats by intramuscular injection. Veterinary Research Communications, 21 (6), 453-462The effect of experimentally induced Pasteurella haemolytica pneumonia on the pharmacokinetics of doxycycline (Doxycen Retard) administered intramuscularly was studied in seven East African dwarf goats. The study was conducted in two consecutive phases, separated by a washout period of four weeks. The experimental infection, induced by intratracheal administration of 5 ml of 107 to 109 cfu/ml of Pasteurella haemolytica, produced a temperature rise, depression and laboured breathing within 6-12 days after inoculation.The concentrations of doxycycline in the serum 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 level of detectability of approximately 0.05 µg/ml. The concentration-time curve of doxycycline in the serum after intramuscular injection of 20 mg/kg bodyweight of the long-acting formulation before and after experimental infection was adequately described by a one-compartment open model.The maximum serum concentrations (Cmax) of doxycycline were lower in pneumonic goats than in healthy goats (3.87 ± 0.52 and 5.56 ± 0.213 µg/ml, respectively), suggesting an increased distribution volume in the peripheral compartment. The mean ± SEM absorption rate (ka) before infection (1.13 ± 0.02 h-1) was smaller than that after infection (8.23 ± 3.81 h-1), but the difference was not significant. The apparent elimination half-life (t1/2β) (24.51 ± 0.02 h) after infection was significantly increased (p < 0.05), while the corresponding rate constant (β) was decreased (p < 0.01). The absorption half-life (t1/2α) (0.137 ± 0.03 h) was significantly decreased (p < 0.01) after infection. The distribution volume (Vd(β)) was significantly increased after infection (p < 0.05). It is concluded that, although experimental infection had an effect on the disposition kinetics of doxycycline, this was not sufficiently pronounced to require alteration of the dosage during disease.

The Pharmacokinetics of a Long-acting Oxytetracycline Formulation in Healthy Dogs and in Dogs Infected with Ehrlichia canis

The pharmacokinetic properties of oxytetracycline were studied following a single injection of a long-acting formulation (20 mg/kg body weight) into the semimembranosus muscle of healthy dogs and of dogs that had been experimentally infected with Ehrlichia canis. The disposition curves of the long-acting oxytetracycline formulation before and after infection were best described by a bi-exponential decline after a first-order absorption. The mean maximum serum concentration (Cmax) following infection was significantly lower and the time taken to attain this concentration (tmax) was significantly shorter than that in the healthy dogs. The mean apparent elimination half-life (t1/2β) was significantly increased following infection. The corresponding rate constant (β) was significantly decreased. The absorption half-life (t1/2ab) was significantly decreased after infection. The volume of distribution at steady state (Vdss) increased significantly following infection. It was concluded that the pharmacokinetic behaviour of a long-acting oxytetracycline in dogs after intramuscular administration is characterized by a two-compartment model with a slow elimination phase. This could be due to flip-flop kinetics. The febrile reaction in experimental E. canis infection affected some pharmacokinetic parameters of oxytetracycline.

Some pharmacokinetic parameters of doxycycline in East African goats after intramuscular administration of a long-acting formulation

A compartmental and non-compartmental study was carried out on five adult goats following intramuscular administration of doxycycline at 20 mg/kg bodyweight. The concentration of the drug in serum was determined by a microbiological assay employingBacillus cereus varmycoides (ATCC 11778) as the test organism. The mean serum concentration (Cmax) and the time of maximum concentration (Tmax) were 1.87 µg/ml and 0.85 h, respectively. Using compartmental analysis, the plasma concentration-time curve of doxycycline best fitted a three-compartment open model with first-order absorption. A three-phase disposition of doxycycline was found, the terminal elimination half-life being approximately 40 h.The statistical moment theory was mainly used for non-compartmental analysis. The value obtained for the mean residence time (MRT) was 16.41 h. The mean values for the volume of distribution at steady state (Vdss), determined by compartmental and non-compartmental analyses, were 8.73 and 13.19 L/kg, respectively. There were no statistically significant differences when the major pharmacokinetic parameters were compared.It was concluded that the pharmacokinetic behaviour of doxycycline in goats after intramuscular administration is characterized by a three-compartment model with a slow terminal elimination phase. Based on current knowledge, this could be due to enterohepatic recycling and/or flip-flop kinetics. The study indicated that a single intramuscular administration of 20 mg/kg of doxycycline may only provide therapeutic concentrations for up to 24 h owing to slow absorption at the injection site.

The Role of Unregulated Sale and Dispensing of Antimicrobial Agents on the Development of Antimicrobial Resistance in Developing Countries

Antimicrobial resistance has become a major medical and public health problem worldwide. This has been brought about by overuse and/or misuse of these drugs especially in developing countries. The role of unregulated sale and dispensing of antimicrobial agents on the development of resistance is presented in this chapter.

Establishment and comparative analyses of different culture conditions of primary hepatocytes from Nile tilapia (Oreochromis niloticus) as a model to study stress induction in vitro

SummaryWe established an in vitro hepatocyte primary culture system from Oreochromis niloticus, a tropical fish species of great economical importance, and evaluated its ability to express albumin, a liver-specific protein, consistently for a period of 3 wk. Serum requirements for fish hepatocyte cultures were assessed. A one-step in situ perfusion of tilapia liver retrogradely followed by collagenase liver dissociation and subsequent washing produced nearly 90% homogenous viable hepatocytes, as shown by trypan blue exclusion test. Mixed primary monolayer and aggregate hepatocyte cultures achieved by 10% fetal calf serum medium supplements expressed consistent levels of albumin. The results of light and electron microscopy showed that the hepatocytes did not significantly proliferate (P<0.05) but remained viable for at least 3 wk. The results of this study show that in vitro cultures of mixed primary hepatocyte monolayers and aggregates established from Nile tilapia may be useful models for studying transient cellular stress induction.

Effects of antiarrhythmic drugs (verapamil propranolol and lignocaine) on the electrocardiogram and haematology in adrenaline-induced arrhythmias in dogs anaesthetized with halothane

Twenty adult (1-3 year old) mongrel dogs of either sex were used to study the effects of antiarrhythmic drugs in adrenaline-induced arrhythmias. The dogs were divided randomly into four groups of five dogs each (n = 5), anaesthetized with halothane and pretreated intravenously (i.v.) with verapamil 0.1 mg kg-1, propranolol 0.06 mg kg-1, or lignocaine 4 mg kg-1 while the controls received sterile physiological saline. Adrenaline (4 micrograms kg-1) was administered i.v. 10 min after drug pretreatments. Lead II of the ECG was recorded and blood collected for haematology. Ventricular fibrillations preceded by ventricular tachycardia occurred in the control dogs and three died within one minute of adrenaline administration. The predominant arrhythmias were ventricular premature beats, ventricular tachycardia, and second degree heart block. A significant increase (P < 0.05) in T wave amplitude was observed in the control group from 0.16 +/- 0.05 mV to 0.43 +/- 0.09 mV while only minimal increases were noted in the drug pretreated groups and there were no deaths. Data obtained from this study suggest that verapamil when administered early compares well with propranolol in the control of adrenaline-induced ventricular arrhythmias in the dog. Lignocaine when administered early prior to the induction of the arrhythmias protected against death but not arrhythmias. Drug pretreatments did not have any clinically significant effects on electrocardiographic parameters.

Acute toxicity studies with quinuronium sulfate in laboratory animals and sheep.

The acute toxicity of quinuronium was investigated by measurements of lethal doses (LD50) in mice and rats, cholinesterase activity in vivo in whole blood, and protection from anticholinesterase activity by atropinisation in sheep and rabbits. The LD50s in mice injected i.p. and s.c. were 4.80 and 5.40 mg/kg and in rats 6.3 and 6.5 mg/kg for i.p. and s.c. routes, respectively. Signs of salivation, defecation, anorexia and muscular spasms were observed in sheep. In rabbits anorexia and depression only were observed. There was species variation in normal cholinesterase activity, rabbits being low in activity. Quinuronium inhibited cholinesterase activity from 10 min to 24 h after treatment in sheep by 24% of the normal baseline values. The enzyme activity returned to normal at 48 h. Atropinisation partially protected against anticholinesterase activity in sheep; cholinesterase activity was inhibited by only 14% of the normal baseline values 10 min to 2 h after treatment. This study indicates that quinuronium is highly toxic and that rabbits are moderately resistant.

The pharmacokinetics of pyrethrins in lactating and non-lactating ewes after oral and subcutaneous administration

Pyrethrins were administered orally and subcutaneously (SC) at 150 mg/kg body weight to 10 lactating and nonlactating ewes in a cross over experimental design. A gas chromatographic method was used for analysis of Pyrethrins in serum and milk samples from the experimental animals. The disposition curves were bi-exponential after first-order absorption and fitted 1 and 2 compartmental models. The maximum plasma concentration (Cmax) of Pyrethrins following oral and SC administration was 0.08 μg/ml and 0.13 μg/ml respectively with the corresponding time to maximum concentrations (Tmax) being 1 hr and 2 hrs respectively. At 48 hours, serum Pyrethrins levels were below the limit of detection of 0.005 μg/ml. Absorption was significantly higher for SC route compared to oral routes (p 0.05). The mean residence time (MRT) was 9.7 hours. Total clearance was 4,337 and 3,180 litres/ kg/hr for oral and SC routes respectively. Pyrethrins were secreted in milk at levels of up to 0.005 μg/ml. It was concluded that in ewes, Pyrethrins are rapidly absorbed after orally and SC, widely distributed and eliminated from the body within 24 hours. Secretion into milk occurs in ewes but the residues in milk are too low to toxic effects in humans.