Pharmacokinetics of controlled-release carbimazole tablets support once daily dosing in cats

Carbimazole, a prodrug of methimazole, is used in the treatment of hyperthyroidism in cats. The pharmacokinetics of methimazole was investigated in healthy cats following oral administration of 15 mg of carbimazole as a controlled-release tablet (Vidalta^®, Intervet). The controlled-release tablet did not produce a pronounced concentration peak and methimazole was present in the circulation for a sustained period, compared with a conventional tablet formulation. The time to reach peak concentrations after carbimazole administration was quite long (t_max 6 h). The absolute bioavailability of carbimazole was around 88 ± 11%. Repeated oral administration daily for 13 consecutive days did not lead to accumulation of methimazole in plasma. The extent of absorption of carbimazole was about 40% higher when administered to cats that had been fed compared to fasted cats. The relative oral bioavailability of methimazole following administration of the controlled-release tablets was similar to that of a conventional release formulation (83 ± 21%). The pharmacokinetics of this controlled-release formulation of carbimazole supports its use as a once daily treatment (both as a starting dose and for maintenance therapy) for cats with hyperthyroidism.     

Pharmacokinetics and bioavailability of ronidazole from a prolonged release tablet in the homing pigeon (Columba livid)

The pharmacokinetics of ronidazole and the bioavailability of a prolonged release tablet were studied in the homing pigeon. After intravenous administration of 5 mg ronidazole, the drug plasma concentration profile fitted a one-compartment open model. The mean half-life of the drug was 11 h and the volume of distribution was 0.86 l/kg. Total body clearance was 0.056 l/h/kg. A sustained release matrix tablet exhibited prolonged drug release in vitro. After oral administration of the matrix tablet to pigeons drug absorption was nearly complete. When given on an empty stomach, the tablet failed as a prolonged release system. Administration to previously fed pigeons resulted in an increase in tmax and a decrease in Cpmax.     

Tiamulin in drinking water for treatment and development of immunity to swine dysentery

The diarrhea of swine dysentery receded in swine treated with 60 or 45 mg of tiamulin/L of drinking water (60 or 45 ppm). However, within 2 to 10 days (average 4.1 days) after drug withdrawal, diarrhea recurred. Tiamulin (22.5 mg/L in drinking water) did not markedly reduce the diarrhea during medication, and tylosin (66 mg/L in the drinking water) was not effective. In swine treated with 120 mg of dimetridazole/L of drinking water, there was no recurrence of diarrhea. After the recurrence of diarrhea in swine, repeated medication with tiamulin in drinking water reduced the severity of diarrhea and prevented deaths. After 1 to 3 retreatments, swine were immune to exposure with swine dysentery inoculum, and there was a significant (P less than 0.05) increase in their serum anti-Treponema hyodysenteriae antibodies. Seemingly, drug withdrawal permitted the occurrence and recurrence of diarrhea that was necessary to stimulate immunity.     

Influence of feeding on the bioavailability of ronidazole prolonged-release formulations in pigeons

The influence of feeding on the bioavailability of ronidazole (5 mg per animal) formulated as a hydrophilic-matrix tablet or as lipophilic pellets, was evaluated in pigeons. Administered to fed pigeons, prolonged drug absorption was obtained for both formulations. In non-fed pigeons an immediate grinding of the formulations in the gizzard resulted in rapid drug absorption. This indicates that prolonged residence of the prolonged-release formulations in the crop obtained in the fed condition seemed the only possible means of obtaining prolonged drug release in pigeons.     

Bioavailability of oxytetracycline, tetracycline and chlortetracycline after oral administration to fed and fasted pigs

The disposition of oxytetracycline (OTC), tetracycline (TC) and chlortetracycline (CTC) was measured after intravenous and oral administration to pigs. Eighteen healthy pigs (six for each compound) weighing 22-43 kg received a dose of 10 mg/kg intravenously, and 45 mg/kg (OTC and TC) or 40 mg/kg (CTC) orally in both a fasted and a fed condition in a three-way crossover design. The three tetracyclines were present in plasma up to 30 hours after intravenous and after oral administration to fasted as well as fed pigs. The volume of distribution was 1.4, 1.2 and 0.7 L/kg body weight for OTC, TC and CTC respectively. The bioavailability was in general low for all the three tetracyclines. The presence of food did not affect the bioavailability of OTC, which was only 3% in both fasted and fed pigs. For TC there was a significantly higher bioavailability in fasted (18%) than in fed (5%) pigs, whereas for CTC the difference was not significant, being 11% in fasted vs. 6% in fed pigs. Even though the presence of food affected the bioavailability only for TC, it prolonged the absorption phase for all three tetracyclines. Based on the bioavailability and the resulting plasma concentrations, it is concluded that it is not possible to obtain a therapeutically active concentration in plasma or tissues after oral administration of any of the three tetracyclines to fed or fasted pigs.     

Non-starch polysaccharides alter interactions between Heterakis gallinarum and Histomonas meleagridis

Nutrition of the host animal may not only influence interactions between the host and its parasites, but also relations between different parasites species residing on the same host. We investigated effects of insoluble and soluble non-starch polysaccharides (NSP) on establishment and development of Heterakis gallinarum in chicken being treated or left untreated against Histomonas meleagridis. Six groups of one-day-old birds were allocated to three diets, two on each diet. The birds were fed ad libitum either a basal diet (CON), or CON+insoluble NSP (I-NSP) or CON+soluble NSP (S-NSP) until an age of 11wk. At an age of 19d, one of each diet groups was prophylactically treated for 9d with dimetridazole (0.05%, w/v) via drinking water against histomonas. The remaining three groups were left un-treated. Two days after starting dimetridazole treatment (at 3wk), each of the 6 groups was divided into two sub-groups. One dimetridazole treated and one dimetridazole un-treated groups of birds on each diet (6 groups) were infected with 200 embryonated eggs of H. gallinarum that were previously harvested from histomonas-carrying H. gallinarum infected chickens. The remaining 6 groups of uninfected birds, either treated or left un-treated against H. meleagridis, served as controls. Worm burdens of infected birds were determined 8wk p.i. Treatment against H. meleagridis significantly increased incidence of H. gallinarum infection and average worm length in all infected groups independent of the diet consumed (p<0.001). An interaction between effects of diet and dimetridazole treatment on worm burden (p<0.001) indicated that the S-NSP diet resulted in lowest worm burden in dimetridazole un-treated birds, whereas it caused the highest worm burden in the treated birds (p<0.05). Furthermore, the treatment resulted in higher worm burdens when compared to un-treated birds on the corresponding diets (p<0.05). Infection with H. gallinarum impaired body weight (BW) of the chicks (p<0.05) and H. meleagridis aggravated this effect (p<0.05). Dimetridazole treated and un-treated uninfected birds developed similar BW (p>0.05). Both NSP supplemented diets resulted in lower (p<0.05) BW when compared with the CON diet, S-NSP being inferior to I-NSP (p<0.05). It is concluded that H. meleagridis harms the definitive host as well as H. gallinarum. Both insoluble and soluble NSP supplemented diets favor H. gallinarum infection while S-NSP additionally intensifies histomonas infection, which then impairs establishment and development of H. gallinarum.     

Pharmacokinetics and bioavailability of erythromycin in pigeons (Columba livia)

Tissue and plasma concentrations were determined after intravenous and oral administration of erythromycin to pigeons to establish the pharmacokinetics and bioavailability of the drug. A short mean half-life of elimination of 0.9 h was found. The relative bioavailability after direct crop administration of erythromycin thiocyanate or erythromycin ethylsuccinate at a dosage rate of 100 mg/kg was less than 10%. At a drug concentration in drinking water of 1 g/l, erythromycin plasma levels were barely detectable, whilst lung and trachea concentrations reached a maximum of 1.6 micrograms/ml. Even after crop administration of 100-mg/kg erythromycin thiocyanate, low plasma levels were obtained, whilst lung and trachea concentrations were substantially higher. Prescribed drinking-water regimens seemed unable to yield therapeutic tissue concentrations. Only individual crop administration seemed an appropriate medication method. The use of erythromycin ethylsuccinate did not present any advantage in comparison with erythromycin thiocyanate.     

Chlortetracycline in swine-bioavailability and pharmacokinetics in fasted and fed pigs

Chlortetracycline hydrochloride was administered intra-arterially (11 mg/kg) and as an oral drench (33 mg/kg) to ten 21.0-31.5-kg pigs. Five of the pigs were fasted 18 h prior to dosing and five of the pigs were fed ad libitum prior to dosing. The mean volume of distribution determined by area-under-the-curve calculations for the fasted pigs (0.967 +/- 0.210 l/kg) was significantly less (P less than 0.05) than the mean volume of distribution for the fed pigs (1.39 +/- 0.31 l/kg). Mean total body clearance of the drug was also significantly less (P less than 0.05) in the fasted pigs (0.165 +/- 0.055 l/kg/h) as compared to the fed pigs (0.307 +/- 0.053 l/kg/h). The elimination constants (beta) were not found to be statistically different (P less than 0.05): 0.1811 +/- 0.0057 for the fasted pigs; 0.2260 +/- 0.0461 for the fed pigs. The bioavailability for both groups was similar; 19.12 +/- 8.3% for the fasted pigs and 17.88 +/- 5.3% for the fed pigs. In a second experiment three groups of six pigs which weighed 34.5-44.1 kg were fed a corn-soy diet ad libitum. The rations were fortified with chlortetracycline at 100, 400 or 1000 mg chlortetracycline hydrochloride/kg feed. Chlortetracycline concentrations were determined in plasma samples collected over a 6-day period. Plasma chlortetracycline concentrations reach a plateau within 24 h after initial access to the trial diets and were highly correlated with the dose of the drug consumed (r2 = 0.97).     

The efficacy of different oral dosage forms of furazolidone for E. coli infections in carrier pigeons

The clinical efficiacy of furazolidon for treatment of E. coli-induced gastro-intestinal infections in racing pigeons was investigated. 36 adult pigeons were treated with 2 different oral modes of application (capsule/drinking water) with a daily therapeutic dosage of 12.5 mg furazolidon/pigeon. The pigeons used for this study (Columba livia f. domestica) originated from conventional breeders and were housed in 3 different groups (control-, capsule- and powder-group) in different stables. After infection with an E. coli-strain (O150:H8) that proved to be pathogenic for pigeons, the animals developed clinical signs of disease within 2 days. After onset of disease the treatment with furazolidon for 5 days started. This phase was followed by an adspectory phase for 6 days. The negative identification of the E. coli O150:H8 was determined as main parameter for the clinical efficiacy of the treatment with furazolidon. This parameter showed a highly significant (p = 0.0001) difference between both groups treated with furazolidon and the control group. In both groups treated with furazolidon the E. coli strain could not be isolated after the end of the treatment. An improvement of clinical signs was seen 24 hours after treatment via capsule and 48 hours after treatment via drinking water formulation. The time difference might be caused by the high concentration of furazolidon in the capsules due to the single daily application. Considering the inaccurate dosing via drinking water that results from the varying drinking water intake in pigeons, the application by capsule should be prefered. Both furazolidon preparations proved to be effective in treating gastro-intestinal E. coli-infections in racing pigeons in a dosage of 12.5 mg/pigeon for 5 days, however, best results were obtained by application via capsule.     

The pharmacokinetics of mavacoxib,a long‐acting COX‐2 inhibitor,in young adult laboratory dogs

Cox, S.R., Lesman, S.P., Boucher, J.F., Krautmann, M.J., Hummel, B.D., Savides, M., Marsh, S., Fielder, A., Stegemann, M.R. The pharmacokinetics of mavacoxib, a long‐acting COX‐2 inhibitor, in young adult laboratory dogs. J. vet. Pharmacol. Therap. 33 , 461–470. The pharmacokinetics of mavacoxib were evaluated in an absolute bioavailability study, a dose‐proportionality study and a multi‐dose study in young healthy adult laboratory Beagle dogs and in a multi‐dose safety study in Beagle‐sized laboratory Mongrel dogs. When administered as the commercial tablet formulation at 4 mg/kg body weight (bw) to fasted dogs, the absolute bioavailability (F) of mavacoxib was 46.1%; F increased to 87.4% when mavacoxib was administered with food. Following intravenous administration, the total body plasma clearance of mavacoxib was 2.7 mL·h/kg, and the apparent volume of distribution at steady‐state was 1.6 L/kg. The plasma protein binding of mavacoxib was approximately 98% in various in vitro and ex vivo studies. The dose‐normalized area under the plasma concentration–time curve was similar in Beagle and Beagle‐sized Mongrel dogs when mavacoxib was administered with food. Mavacoxib exhibited dose‐proportional pharmacokinetics for single oral doses of 2–12 mg/kg in Beagle dogs and for multiple oral doses of 5–25 mg/kg in Beagle‐sized Mongrel dogs. Only minor accumulation occurred when mavacoxib was administered at doses of 2–25 mg/kg bw orally to laboratory dogs with a 2‐week interval between the 1st two doses but with a monthly interval thereafter. Across all three Beagle studies (n = 63) the median terminal elimination half‐life (t_½) was 16.6 days, with individual values ranging 7.9–38.8 days. The prolonged t_½ for mavacoxib supports the approved regimen in which doses are separated by 2–4 weeks.     

Pharmacokinetics, safety and tissue residues of sustained-release sulfamethazine in sheep

Concentration-time profiles and the rates of absorption, extent of distribution and half-lives of sulfamethazine (SMZ), administered intravenously, orally as a water solution and as a sustained-release formulation (CalfSpan) were determined in 10 healthy sheep. The geometric mean half-life of elimination of i.v. SMZ was 10.8 h, compared to 14.3 h for the sustained-release preparation (CalfSpan) and 4.3 h for the oral water solution. Blood levels of SMZ were at or above 50 micrograms/ml for more than 48 h for CalfSpan, for 24 h after i.v. SMZ (100 mg/kg body wt), and for less than 24 h after p.o. SMZ (100 mg/kg body wt). The mean bioavailability of the oral SMZ solution was 58.3% (AUCp.o./AUCi.v.). The estimated bioavailability of the CalfSpan preparation was 52.5%. The safety of the sustained-release preparation was tested by dosing sheep with multiples (one, three and five times) of the recommended dose (one tablet, 8 g SMZ, per 20 kg body wt), once a day for 3 days. Clinical blood chemistries showed a significant increase in serum iron, and a decrease in serum phosphorus in animals treated at the 3x and 5x dose levels. Necropsies of the 5x dose animals did not show any gross signs that could be attributed to SMZ, and histological examination of tissues from the 5x animals revealed no organ pathology. Residues of SMZ in liver, fat, kidney and skeletal muscle were measured in 20 animals that received one bolus per 20 kg body wt. The results indicate that SMZ residues are cleared rapidly, and are at or below the tolerance level of 0.1 mg/kg within 8 days after dosing so that the 18-day withdrawal time used in cattle would provide an appropriate margin of safety if used in sheep.     

The pharmacokinetics of maropitant, a novel neurokinin type-1 receptor antagonist, in dogs

Maropitant is the first NK1 receptor antagonist developed to treat and prevent emesis in dogs; it is administered by subcutaneous (s.c.) injection at 1 mg/kg, or orally (p.o.), in tablet form, at either 2 or 8 mg/kg depending on indication. The absolute bioavailability of maropitant was markedly higher (90.7%) following s.c. injection than after oral administration (23.7% at the 2 mg/kg dose and 37.0% at the 8 mg/kg dose). First-pass metabolism contributes to the low bioavailability of maropitant following oral administration. The difference in bioavailability between the two oral doses reflects the nonlinear kinetics characterizing the disposition of maropitant within the 2-8 mg/kg dose range. Systemic clearance of maropitant following intravenous (i.v.) administration was 970, 995 and 533 mL/h.kg at doses of 1, 2 and 8 mg/kg, respectively. Nonproportional kinetics were observed for p.o. administered maropitant at doses ranging from 2 to 16 mg/kg but dose proportionality was demonstrated at higher doses (20-50 mg/kg). Linearity was also demonstrated following s.c. administration at 0.5, 1 and 2 mg/kg. Maximum plasma drug concentration (Cmax) occurred 0.75 h (tmax) after s.c. administration at 1 mg/kg, and at 1.7 and 1.9 h after oral administration of 8 and 2 mg/kg doses, respectively. The apparent terminal half-life of maropitant was 7.75, 4.03 and 5.46 h after dosing at 1 mg/kg (s.c.), 2 mg/kg (p.o.) and 8 mg/kg (p.o.), respectively. Feeding status had no effect on oral bioavailability. Limited accumulation occurred following once-daily administration of maropitant for five consecutive days at 1 mg/kg (s.c.) or 2 mg/kg (p.o.). At the dose of 8 mg/kg (p.o.) once daily for two consecutive days, the mean AUC(0-24h) (second dose) was 218% that of the first dose value. Urinary recovery of maropitant and its main metabolite was minimal (<1%), thus supporting the evidence that maropitant clearance is primarily hepatic.     

Minimal inhibitory concentrations of five antimicrobials against Treponema hyodysenteriae and Treponema innocens

The minimal inhibitory concentrations of carbadox, dimetridazole, lincomycin, ronidazole, and tiamulin against isolates of Treponema hyodysenteriae and Treponema innocens were determined by an agar-dilution method. The results obtained indicated that tiamulin was the most effective antimicrobial in vitro against T. hyodysenteriae, followed by carbadox. Dimetridazole, lincomycin, and ronidazole had poor efficacy in vitro against the T. hyodysenteriae isolates. Isolates of T. innocens were more sensitive to the various antimicrobials. Carbadox and tiamulin were the most effective in vitro, followed by ronidazole, dimetridazole, and lincomycin.     

The effect of sucralfate tablets vs. suspension on oral doxycycline absorption in dogs

The purpose of this study was to determine the effect of concurrent sucralfate (tablet or suspension) on doxycycline pharmacokinetics and to determine the effects of delaying sucralfate by 2 h on doxycycline absorption. Five dogs were included in a crossover study receiving: doxycycline alone; doxycycline concurrently with sucralfate tablet; doxycycline followed 2 h by sucralfate tablet; doxycycline concurrently with sucralfate suspension; and doxycycline followed 2 h by sucralfate suspension. Doxycycline plasma concentrations were evaluated with liquid chromatography with mass spectrometry. No interaction was seen when sucralfate was administered as a tablet. Sucralfate tablet fragments were frequently observed in some dogs' feces. The area under the curve (AUC) and maximum plasma concentration (C_MAX) were significantly lower (P < 0.001) in the concurrent sucralfate suspension group (AUC 7.2 h·μg/mL, C_MAX 0.43 μg/mL) than with doxycycline alone (AUC 36.0 h·μg/mL, C_MAX 2.53 μg/mL) resulting in a relative bioavailability of 20%. Delaying sucralfate suspension by 2 h after doxycycline administration resulted in no difference in doxycycline absorption as compared with doxycycline administration alone with a relative bioavailability of 74%. The lack of an interaction with sucralfate tablets suggests sucralfate should be administered as a suspension rather than tablet in dogs.     

The effect of soybean oil refuse powder used as vehicle on the absorption of oxolinic acid in chickens under fasting and nonfasting conditions and the correlation with in vitro dissolution

The effect of soybean oil refuse powder (SOR) when used as a vehicle on the absorption of oxolinic acid (OXA) powder in chicken, the dissolution profile of OXA and the correlation between in vivo and in vitro study were examined. To examine in vivo bioavailability, chickens fed or fasted were studied using a 2 x 2 crossover design. The OXA was administered OXA or OXA-SOR (1 : 9) mixture 20 mg OXA/kg. In vitro dissolution rates for OXA and OXA-SOR were measured using the paddle (PD) and the rotatory dialysis cell dissolution (PTSW) methods. Maximum plasma concentration (Cmax) and area under the curve (AUC) were significantly increased by the addition of SOR to OXA. Differences between OXA and OXA-SOR were more remarkable under fasted as compared with fed condition. In vitro dissolution rates of OXA-SOR pH 1.2, 6.5 and 7.2 as determined by the PD and the PTSW methods were increased in the presence of SOR vehicle. Differences between OXA and OXA-SOR in vitro dissolution rates were greater than in vivo bioavailability. Correlation between in vitro release (%) and in vivo absorption (%) showed good linearity (gamma=0.8805-0.9999).     

Bioavailability of oral penicillins in the horse: a comparison of pivampicillin and amoxicillin

The pharmacokinetics of ampicillin and amoxicillin following intravenous administration at a dose rate of 15 and 10 mg/kg respectively were studied in four healthy adult horses. Pharmacokinetics of pivampicillin and amoxicillin were studied after oral administration to four healthy adult horses. Pivampicillin, a prodrug of ampicillin, was administered orally to starved and fed horses at a dose rate of 19.9 mg/kg, which is equivalent on a molecular basis to 15 mg/kg ampicillin. Amoxicillin was administered orally to starved horses only, at a dose rate of 20 mg/kg. Ampicillin and amoxicillin concentrations in plasma, synovial fluid and urine were determined. Mean biological half-life of intravenously administered ampicillin and amoxicillin was 1.72 and 1.43 h respectively, whilst the distribution volume (Vss) appeared to be 0.180 and 0.192 1/kg. Orally administered pivampicillin and amoxicillin were rapidly absorbed. A maximum concentration in plasma of 3.80 micrograms/ml was reached 2 h after administration of pivampicillin to starved horses; in fed horses a maximum concentration of 5.12 micrograms/ml was reached 1 h after administration. After oral administration of amoxicillin a maximum concentration of 2.03 micrograms/ml was reached after 1 h. The (absolute) bioavailability of pivampicillin administered orally was 30.9% in starved horses and 35.9% in fed horses. The bioavailability of amoxicillin administered orally was 5.3% in starved horses.     

The efficacy of some drugs with known antiprotozoal activity against Histomonas meleagridis in chickens

Nine drugs with known or suspected antiprotozoal activity were tested in vitro, and in vivo for activity against Histomonas meleagridis. The nitroimidazoles dimetridazole, metronidazole, ornidazole, and tinidazole suppressed growth of H. meleagridis in vitro at 10 microg/ml or higher. Paromomycin sulfate, and carbadox were weakly effective at high levels. Quinolinol, mebendazole, diloxanide furoate, and albendazole had no demonstrable efficacy in vitro. Drugs showing some activity in vitro were tested in young chickens inoculated intracloacally with 2 x 10(5) H. meleagridis/bird. Dimetridazole, metronidazole, ornidazole, and tinidazole were highly effective at 200 ppm in feed. Paromomycin sulfate, and carbadox were ineffective in vivo, with no improvement in liver or cecal lesion scores compared to that of infected controls. Thus, the only new entities with efficacy against blackhead disease in vivo were nitroimidazoles, related to the positive control dimetridazole.     

Pharmacokinetics, tolerance and serum thromboxane inhibition of carprofen in the dog

The non-steroidal anti-inflammatory drug (NSAID) carprofen was administered to dogs as a mixed-micelle solution at a dose rate of 0–7 mg/kg intravenously, as a palatable paste at a dose rate of 0–7 mg/kg orally, and as an oral tablet formulation at a dose rate of 0–7 mg/kg and 4-0 mg/kg orally for pharmacokinetic studies. It was also administered as an oral tablet formulation at a dose rate of 9-0 mg/kg orally daily for 14 days in a tolerance study. The pharmacokinetics following intravenous administration at a dose rate of 0–7 mg/kg indicate that carprofen has a small volume of distribution (Vd area = 0–09-0-25 litres), a slow systemic clearance (Cls = 1–34-5-57 ml/min) and an elimination half-life of 3–20-11-77 hours. Both oral paste and tablet preparations were highly bioavailable and absorption was proportional to dose rate at 0–7 mg/kg and 4-0 mg/kg bodyweight. Given once daily at dose rates likely to be used clinically it is unlikely to accumulate in the plasma. Carprofen administered as a palatable paste at a dose rate of 0–7 mg/kg did not inhibit serum thromboxane generation and this drug may therefore have a mode of action different from most NSAIDs. Carprofen was well tolerated when administered as an oral tablet formulation at a dose rate of 9.0 mg/kg daily for 14 days in healthy beagle dogs.     

Bioavailability of amoxycillin in pigs

Amoxycillin was administered to pigs intravenously (i.v.), intramuscularly (i.m.) and orally (p.o.), in a cross-over design to examine the bioavailability ( F ) of various drug formulations. These included: a sodium salt for reconstitution in water and administration i.v.; trihydrate salt in an oil base for intramuscular administration producing 'conventional' duration of plasma concentrations; a trihydrate salt in oil base giving prolonged (LA) duration, and a trihydrate powder for oral administration in solution. The concentration of amoxycillin in plasma was measured by high-performance liquid chromatography, and its pharmacokinetic variables were assessed for the individual pigs by use of non-compartmental methods.
  Following i.v. administration (8.6 mg/kg), amoxycillin was eliminated rapidly with a mean residence time ( MRT ) of 1.4 h. After i.m. administration of the conventional formulation (14.7 mg/kg), the plasma amoxycillin concentration peaked at 2 h at 5.1 μg/mL. The bioavailability was 0.83. Intramuscular administration (14.1 mg/kg) of the long acting formulation (i.m. LA), lead to two peaks in plasma at 1.3 and 6.6 h. The bioavailability was calculated to be 1.11. After p.o. administration to fasted pigs, peak concentration was reached after 1.9 h, and the bioavailability was 0.33. In fed pigs, the corresponding values were 3.6 h and 0.28. Data showed that treatment of respiratory tract diseases in pigs by p.o. dosing alone, may not be optimal, because of the relatively low bioavailability and the fact that infections often result in reduced feed and water consumption. A rational treatment regime for susceptible respiratory pathogens includes an initial i.m. injection, followed by p.o. dosing every 12 h. Alternatively, the long acting formulation may be administered i.m. in a dose of 15 mg/kg, which would lead to active plasma concentrations for approximately 48 h.     

Pharmacokinetics of cimetidine in dogs after oral administration of cimetidine tablets

Long-term oral treatment with cimetidine is recommended to reduce vomiting in dogs with chronic gastritis. Despite this, few studies have specifically examined the plasma disposition and pharmacokinetics of cimetidine in dogs, particularly following repeated oral administration. The pharmacokinetics of cimetidine following oral administration as tablets was investigated in healthy dogs. Cimetidine was absorbed rapidly post-treatment ( t _max = 0.5 h). A mean absolute bioavailability of 75% was calculated following a single oral administration of 5 mg cimetidine/kg body weight. After intravenous administration, a plasma half-life of 1.6 h was calculated. Repeated oral administration at the recommended dose rate and regime (5 mg/kg body weight three times daily) for 30 consecutive days did not lead to any accumulation of cimetidine in plasma. Food intake concomitant with oral administration of cimetidine delayed ( t _max = 2.25 h) and decreased the rate and extent of absorption ( AUC ) by about 40%. Cimetidine was well absorbed in fasted dogs. Administration of food decreased the bioavailability of cimetidine by 40%. Cimetidine does not accumulate over time in plasma when administered long term to dogs.