A. G. Vulto

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.

In vitro susceptibility to antimicrobial drugs of 62 Salmonella strains isolated from horses in The Netherlands

The in vitro activity of 17 antimicrobial drugs against strains of Salmonella typhimurium (n = 52), Salmonella thompson (n = 2), Salmonella heidelberg (n = 3), Salmonella hadar (n = 2), Salmonella enteritidis (n = 1), Salmonella infantis (n = 1) and Salmonella derby (n = 1) was tested using the agar dilution method. The strains were isolated from horses admitted to the Large Animal Clinics of Utrecht University. The majority of strains were susceptible to gentamicin, amikacin, kanamycin, enrofloxacin, ciprofloxacin, flumequine, colistine, furazolidone and ceftiofur. However, all strains of Salmonella typhimurium phage type 200 (n = 14), were multiresistant i.e. were resistant to ampicillin amoxycillin, amoxycillin in combination with clavulanic acid, chloramphenicol, nitrofurantoin, trimethoprim, aditoprim and baquiloprim. Two of these strains were also resistant to gentamicin. Based on the susceptibility data found in the present study in combination with pharmacokinetic data available in the literature a rationale for antimicrobial therapy in equine salmonellosis is given. As first choice, gentamicin at a dosage of 3 mg/kg combined with ampicillin at a dosage of 20 mg/kg given with a 8-12 hour dosing interval by intravenous route is advised. As an alternative, the intravenous administration of trimethoprim/sulfonamide combinations given twice daily at a combined dose of 30 mg/kg is suggested.

Drug lipophilicity and release pattern of some β-blocking agents after intra-adipose injection in pigs

Abstract Release rates from intramuscular and intra-adipose injection sites have turned out to be dependent upon several factors including injection depth. Little is known about the interaction between drug lipophilicity and transport rate of drugs through adipose and muscle tissue. The principal objective of the present study was to determine to what extent drug lipophilicity affects release and release rate from adipose tissue. Nine pigs were given intravenous (0.1 mg/kg), intramuscular (0.2 mg/kg) and intra-adipose (0.2 mg/kg) injections of propranolol, alprenolol, carazolol, metoprolol and atenolol. The fraction not-absorbed vs time plots after intramuscular and intra-adipose injection showed a biphasic decline for all model compounds with the exception of atenolol being the most hydrophilic drug. This biphasic decline indicates that two different mechanisms may be involved in drug release. Initial release rates after intra-adipose injection were negatively correlated (Kendalls rank order test) with fat-buffer partition constants. The second release phase was best characterized by the extent of 24 h release. The amounts (mean ± S.D.) released after 24 h for propranolol, alprenolol, carazolol, metoprolol and atenolol are 42 ± 15, 38 ± 9, 45 ± 18, 48 ± 12 and 99 ± 12% following intra-adipos injection and 57 ± 8, 36 ± 18, 38 ± 15, 55 ± 14 and 104 ± 14% after intramuscular injection, respectively. Incomplete release at 24 h can be explained by the sunk solvent drag after absorption of the solvent is complete. Octanol-buffer partition and pig-fat-buffer distribution constants turned out to be positively correlated.