Biomedical subjects
J M Ensink
Publications and source records attributed to J M Ensink.
Side effects of oral antimicrobial agents in the horse: a comparison of pivampicillin and trimethoprim/sulphadiazine.
To evaluate the side effects of oral pivampicillin and trimethoprim/ sulphadiazine, 200 horses receiving these antimicrobial agents were studied. The horses received either trimethoprim/ sulphadiazine (30 mg/kg twice daily) or pivampicillin (25 mg/kg twice daily) for three or more days. No adverse effects other than loose faeces and diarrhoea were detected. The risk of diarrhoea was significantly less after the oral administration of pivampicillin (3 per cent) than after trimethoprim/ sulphadiazine (7 per cent). Horses whose appetite was reduced appeared to be predisposed to develop diarrhoea after the administration of either oral antimicrobial agent.
Distribution of penicillins into subcutaneous tissue chambers in ponies.
The distribution of penicillins into a tissue chamber implanted subcutaneously in ponies was studied. Ampicillin sodium (equivalent to 15 mg/kg ampicillin) was administered intravenously. Pivampicillin, a prodrug of ampicillin, was administered by nasogastric tube to fed ponies at a dose of 19.9 mg/kg (equivalent to 15 mg/kg ampicillin). Procaine penicillin G was administered intramuscularly at a dose of 12 mg/kg (equivalent to 12000 IU/kg). Six ponies were used for each medication. Antibiotic concentrations in plasma and tissue chamber fluid (TCF) were measured for 24 h after administration. Mean peak concentrations of ampicillin in TCF were 7.3 micrograms/mL, reached at 1.7 h, and 1.3 micrograms/mL, reached at 2.7 h, after administration of ampicillin sodium and pivampicillin respectively. The mean peak concentration of penicillin G of 0.3 microgram/mL was reached 12.3 h after administration of procaine penicillin G. Concentrations in TCF remained above the minimum inhibitory concentration of Streptococcus zooepidemicus for the proposed dosing intervals of 8, 12 and 24 h for ampicillin sodium, pivampicillin and procaine penicillin G respectively.
Clinical efficacy of ampicillin, pivampicillin and procaine penicillin G in a soft tissue infection model in ponies.
Tissue chambers, implanted subcutaneously in ponies, were inoculated with Streptococcus zooepidemicus. The animals received either no antibiotics or one of the following treatments: pivampicillin per os (19.9 mg/kg, equivalent to 15 mg/kg ampicillin, every 12 h) for 7 or 21 days (7 and 5 ponies, respectively), procaine penicillin G intramuscularly (12 mg/kg = 12,000 IU/kg, every 24 h) for 7 days (7 ponies), or ampicillin sodium intravenously (equivalent to 15 mg/ kg ampicillin, every 8 h) for 1 day (5 ponies). Only intravenous administration was started before infection (prophylactically), the other treatments were started 20 h after infection (curatively). A total of 7 ponies received no antibiotics. In untreated controls, the infection led to abscessation of the tissue chamber in 4 to 10 days. Curative treatment with either pivampicillin or procaine penicillin G for 7 days resulted in a reduction of viable bacteria in the tissue chamber but did not eliminate the infection, resulting in abscessation in 5 to 14 days. However, administration of pivampicillin for 21 days eliminated the streptococci in five out of five ponies and prophylactic administration of ampicillin was successful in three out of five ponies.
Oral bioavailability and in vitro stability of pivampicillin, bacampicillin, talampicillin, and ampicillin in horses.
OBJECTIVES: To determine the oral bioavailabilities of 3 ampicillin esters (pivampicillin, bacampicillin, and talampicillin) and ampicillin sodium, and to determine in vitro stability of the ampicillin esters in ileal contents (pH 8.3 to 8.5). DESIGN: A crossover design to administer the 4 drugs orally, and ampicillin i.v. to all horses in the study. ANIMALS: 4 healthy adult horses. PROCEDURE: The drugs were administered intragastrically to the horses at a dosage equimolar to 15 mg of ampicillin/kg of body weight. Also, ampicillin sodium was administered i.v. at the same dosage. Blood samples were taken up to 12 hours after drug administration, and ampicillin concentrations in plasma were determined. For the in vitro study, the ampicillin esters were incubated at 37 C in ileal contents obtained from ponies with cecal fistulas. After incubation, the remaining intact ester and the formed ampicillin were measured. RESULTS: Absolute oral bioavailability was 31, 39, 23, and 2% for pivampicillin, bacampicillin, talampicillin, and ampicillin sodium, respectively. In the in vitro study, 90% decomposition of the ester took place in 30, 60, and 5 minutes, for pivampicillin, bacampicillin, and talampicillin, respectively. CONCLUSIONS: Pivampicillin and bacampicillin are promising candidates for oral antibiotic treatment of horses. The rapid decomposition of ampicillin esters is caused by chemical hydrolysis at the high pH of equine ileal contents.
Bioavailability of pivampicillin and ampicillin trihydrate administered as an oral paste in horses.
Pivampicillin was administered as an oral paste to five healthy adult horses, and an oral paste with ampicillin trihydrate was administered to three horses. Pivampicillin was administered to both starved and fed horses, ampicillin trihydrate was administered to fed horses only. The dose of pivampicillin was 19.9 mg/kg, and the dose of ampicillin trihydrate was 17 mg/kg. Both doses are equivalent on a molecular basis to 15 mg/kg ampicillin. Ampicillin concentrations in plasma were determined up to 24 hours after administration. After administration of pivampicillin to starved and fed horses the mean areas under the plasma concentration-time curve (AUCs) were 23.0 and 19.3 micrograms.h.ml-1, respectively. After administration of ampicillin trihydrate to fed horses the mean AUC was 0.7 microgram.h.ml-1. The peak plasma concentrations were 4.8, 6.7, and 0.1 microgram/ml, after administration of pivampicillin to starved and fed horses and of ampicillin trihydrate to fed horses, respectively. There was no statistically significant difference in peak plasma concentration or AUC between pivampicillin administered to starved or fed horses. It is concluded that pivampicillin administered as an oral paste at a dose of 19.9 mg/kg gives satisfactory plasma concentrations in both starved and fed horses, whereas ampicillin trihydrate produces negligible plasma concentrations. Pivampicillin binds to feedstuffs at the pH found in the horse's stomach and small intestine. After incubation for 6 h at pH 6, approximately 15% remains in solution, and after incubation for 3 h at pH 1.9, approximately 40% remains in solution. Ampicillin, which binds to feedstuffs to a lesser extent, has a lower bioavailability than pivampicillin. Therefore, binding to feedstuffs does not seem to be a critical factor in the absorption of aminopenicillins.
Single intraoperative administration of antibiotic to cows with caecal torsion: wound infection and postoperative performance. A retrospective and prospective study.
Wound infection and postoperative performance after a single intra-abdominal administration of 9 g sodium ampicillin in cows operated on for caecal dilatation or torsion (n = 33) were evaluated. In the 25 animals that left the clinic in good health (76% short-term survival), no wound infection occurred. Postoperative performance was normal in 21 of these animals (84%). The figures for short-term survival and postoperative performance are comparable to those from a retrospective study of 169 animals operated on between 1985 and 1990. Single intra-abdominal administration of sodium ampicillin during surgery provides good protection against infection without negative effects on the postoperative performance.
Oral bioavailability of pivampicillin in foals at different ages.
The plasma disposition of ampicillin after intravenous administration at a dose rate of 15 mg/kg was studied in six healthy, 1-month-old foals. The oral bioavailability of pivampicillin was determined in the same foals at four ages, ranging from 11 days to 4 months. Pivampicillin was administered orally at a dose rate of 19.9 mg/kg, which is equivalent on a molecular basis to 15 mg/kg ampicillin. Ampicillin concentrations in plasma were determined up to 12 hours after administration. After intravenous administration, the mean distribution and elimination half-lives of ampicillin were 0.121 and 0.624 h, respectively. The volume of distribution (Vss) appeared to be 0.334 l/kg. Orally administered pivampicillin was rapidly absorbed in all age groups, producing mean peak plasma concentrations of 3.83 to 5.69 micrograms/ml 1 h after administration. The mean bioavailability of pivampicillin in the different age groups ranged from 39.4 to 52.9%. There was no statistically significant difference in peak plasma concentration or bioavailability between the age groups. It is concluded that pivampicillin at a dose rate of 19.9 mg/kg orally gives satisfactory plasma concentrations in foals of all ages.
In-vitro susceptibility to antimicrobial drugs of bacterial isolates from horses in The Netherlands.
Minimum inhibitory concentrations (MICs) of 30 antimicrobial agents (including the hitherto unreported antimicrobial agents doxycycline, minocycline, vanomycin, 3 quinolones and 3 combinations of antimicrobial agents) for isolates of Salmonella spp. (20), Escherichia coli (17), Klebsiella spp. (8), Proteus spp. (7), Pseudomonas aeruginosa (7), Actinobacillus equuli (5), Rhodococcus equi (4), Streptococcus zooepidemicus (23), Streptococcus equisimilis (6), Streptococcus equi (4), coagulase-positive Staphylococcus spp. (20) and Taylorella equigenitalis (19) were determined using the agar dilution method. All isolates were of equine origin. MICs were compared with recommended MIC breakpoints. The results indicate that, for some of the pathogenic bacteria evaluated, susceptibility testing of isolates from the individual patient is essential to determine an appropriate antimicrobial treatment.
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.
Comparative aspects and sex differentiation of plasma sulfamethazine elimination and metabolite formation in rats, rabbits, dwarf goats, and cattle.
Plasma disposition and urinary recovery of sulfamethazine (SMZ), its N4-acetylated metabolite (N4AcSMZ), and 2 of its hydroxylated metabolites--5-hydroxysulfamethazine (5OHSMZ) and 6-hydroxymethylsulfamethazine (6CH2OHSMZ)--were determined in either sex of 4 animal species: rats, dwarf goats, rabbits, and cattle. Rats, rabbits, and dwarf goats had significant (P < 0.01) sex difference in SMZ plasma clearance. Male rats had higher plasma clearance than did female rats, and excreted higher amounts of the hydroxy metabolites and lower amounts of N4AcSMZ. The N4AcSMZ metabolite was predominant in plasma and urine of rabbits. Male rabbits had higher plasma clearance than did female rabbits, but differences in metabolite profile were not apparent. With regard to plasma SMZ elimination, the situation in goats was opposite to that in rats. Male goats had considerably lower clearance than did female goats. This was associated with a lower hydroxylation rat in males. Plasma half-life of SMZ in cows was lower than that in bulls, probably because of a smaller distribution volume in cows. Compared with elimination via urine, elimination via milk was negligible in cows. Significant differences in metabolite profiles were not found between bulls and cows. Similar to those in rats and mice, hormone-dependent xenobiotic metabolic pathways may exist in other species. Depending on species and xenobiotic compound residue concentrations of xenobiotics, their metabolites, or both may differ with sex of the animal, or may be altered after treatment with anabolic hormones.
[2 cases of 'hardware' foreign objects in ponies].
An obstruction of the small intestine was suspected in two ponies with colic. At surgery and at necropsy, the cause of the colic appeared to be an inflammation process caused by perforation of the jejunum by a piece of wire. One pony recovered after laparotomy and enterectomy, but had to be put down eight weeks later because of severe laminitis. The other pony was euthanized immediately after clinical evaluation.