In vitro elution studies of amikacin and cefazolin from polymethylmethacrylate

OBJECTIVE: To compare the in vitro elution characteristics of amikacin and cefazolin from polymethylmethacrylate (PMMA) alone and in combination. STUDY DESIGN: A prospective, controlled, experimental study. METHODS: Three aliquots of 6 g sterile PMMA were measured and to them added (1) 750 mg amikacin; (2) 1050 mg cefazolin; and (3) 750 mg amikacin and 1050 mg cefazolin. Ten beads of each antimicrobial/PMMA combination were placed in 5 mL phosphate-buffered saline (PBS) at pH 7.4 and room temperature with constant agitation. PBS was sampled at 15 time points between 1 hour and 30 days. Amikacin concentrations were determined by fluorescence polarization immunoassay and cefazolin concentrations by high-performance liquid chromatography. RESULTS: Amikacin and cefazolin eluted at concentrations greater than 8 and 4 times, respectively, above the minimum inhibitory concentration (MIC) for susceptible bacteria over 30 days. Co-elution of the antibiotics resulted in a greater rate and proportion of antibiotic eluted. Concentrations of amikacin and cefazolin in the co-eluted fluid were not maintained sufficiently above the MIC for selected bacteria over 30 days. CONCLUSIONS: PMMA beads of only amikacin or cefazolin-eluted concentrations greater than the MIC for selected bacteria for 30 days. Co-elution of the antibiotics at the selected doses resulted in a significantly shorter duration of elution and may not be effective for treatment of wound infection. CLINICAL RELEVANCE: Co-elution of amikacin and cefazolin from PMMA at the selected doses cannot be recommended for sustained treatment of infection.     

Elution of metronidazole and gentamicin from polymethylmethacrylate beads

OBJECTIVE: To characterize the elution and bioactivity of metronidazole and gentamicin sulfate polymerized, individually and in combination, with polymethylmethacrylate (PMMA). STUDY DESIGN: In vitro experimental study. METHODS: PMMA beads containing metronidazole (3 concentrations), gentamicin sulfate, or metronidazole and gentamicin sulfate were immersed in 5 mL of phosphate-buffered saline in triplicate. Eluent was replaced at specified time intervals for 1 or 21 days, and antibiotic concentrations were measured by high-performance liquid chromatography. Changes in antibiotic bioactivity attributable to polymerization or copolymerization of the antibiotics with PMMA, ethylene oxide sterilization, and storage of AIPMMA beads containing metronidazole were evaluated. RESULTS: Antibiotic elution patterns were similar for all groups. Day 1 elution for groups containing metronidazole or gentamicin individually represented a mean 63%-66% and 79%, respectively, of the 21-day total. Approximately 50% of the day 1 elution occurred during the first hour. The elution of metronidazole was dose dependent. The elution of metronidazole (day 3-21) and gentamicin (all days) was significantly greater when metronidazole and gentamicin were combined (P <.05). The addition of metronidazole delayed polymerization of PMMA. Neither polymerization nor copolymerization of metronidazole and gentamicin with PMMA, gas sterilization, or 2-month storage of beads containing metronidazole significantly affected antimicrobial bioactivity. CONCLUSIONS: Metronidazole elution from PMMA was dose dependent. Copolymerization of metronidazole and gentamicin sulfate in PMMA resulted in increased rates of elution. Intraoperative preparation of metronidazole-impregnated PMMA beads is not practical, but sterilization and storage for 2 months should not affect efficacy. CLINICAL RELEVANCE: The local delivery of biologically active metronidazole and gentamicin by elution from PMMA is feasible.     

In vitro evaluation of antibiotic elution from polymethylmethacrylate (PMMA) and mechanical assessment of antibiotic-PMMA composites

OBJECTIVE: To determine whether different methods of sterilization of antibiotic vials or the heat of polymerization altered the antimicrobial activity or mechanical properties of antibiotic/polymethylmethacrylate (PMMA) composites when compared to antibiotic-free PMMA. STUDY DESIGN: In vitro study. METHODS: Steam-sterilized, gas-sterilized, and non-sterilized 1 gram vials of cefazolin and injectable gentamicin sulfate (high and low doses) were mixed with PMMA to prepare composites for antibiotic elution evaluation, compression, and elongation testing. Blocks of PMMA that contained antibiotic were assayed for antibacterial activity using an agar gel diffusion method or were placed in phosphate buffered saline (PBS) to assess elution of antibiotic. Phosphate buffered saline samples from steam-sterilized cefazolin and high-dose gentamicin groups were assayed on days 1, 2, 5, and 9 for cefazolin or gentamicin concentration by high-pressure liquid chromatography or fluorescent polarization immunoassay, respectively. RESULTS: PMMA blocks containing antibiotic inhibited bacterial growth of Staphylococcus aureus 25923 for an average of 9 days. Cefazolin and gentamicin concentration in PBS decreased dramatically after the first 24 hours, but remained above minimum inhibitory concentration (MIC) throughout the experiment for all groups except low-dose gentamicin. Compressive strength of plugs made from plain cement and plugs made from PMMA mixed with untreated and steam-sterilized cefazolin was similar, but was significantly different from the other groups. There appeared to be an inverse relationship between compressive strength and elongation. CONCLUSION: PMMA/antibiotic composites inhibited bacterial growth for 7 to 10 days. Compressive strength was affected by different additions of antibiotic. CLINICAL RELEVANCE: Bacteria introduced during a surgical procedure may be inhibited by elution of antibiotic from PMMA at the time of contamination.     

In vitro elution of gentamicin from Plaster of Paris beads

OBJECTIVE: To determine the in vitro elution characteristics of gentamicin from Plaster of Paris-gentamicin (POP-gent) beads. STUDY DESIGN: In vitro, controlled, experimental study. METHODS: The POP-gent beads were made using a bead mold from 20 g calcium sulfate hemihydrate, 5 mL (500 mg) gentamicin solution, and 3 mL of phosphate buffered saline (PBS). Control beads were made similarly, using 30 g of dried powder and 8 mL of PBS. Beads were left in the mold overnight, gas-sterilized with ethylene oxide, and stored at room temperature for 5 months before testing. Bead chains were placed in sterile tubes containing porcine serum, and tubes were placed in a 37 degrees C incubator on a rocker. Serum was removed at intervals over 14 days and the concentration of gentamicin determined by fluorescent polarization immunoassay. Serum antibacterial activity was determined against an equine origin Escherichia coli. RESULTS: POP-gent beads released gentamicin for the 14-day sampling period. Eighty percent of the gentamicin incorporated in the beads was released over the first 48 hours. Eluent from POP-gent beads inhibited the growth of E coli at all time periods. No gentamicin was eluted from control beads and control eluent did not inhibit growth of E coli. CONCLUSIONS: In this experimental model, POP-gent beads released bactericidal drug for 14 days. Eighty percent of the gentamicin incorporated into the beads was released during the first 48 hours. The drug retains its bactericidal activity after ethylene oxide sterilization and storage at room temperature for up to 5 months. CLINICAL RELEVANCE: Pop-gent beads may be a useful repository device to deliver gentamicin locally in tissues.     

In vitro elution of gentamicin, amikacin, and ceftiofur from polymethylmethacrylate and hydroxyapatite cement

OBJECTIVE: To compare the elution characteristics of ceftiofur and liquid and powdered gentamicin and amikacin from polymethylmethacrylate (PMMA) and from hydroxyapatite cement (HAC). METHODS: PMMA and HAC beads in triplicate were impregnated with various amounts and formulations of antibiotics. Beads were immersed in 5 mL of phosphate buffered saline that was replaced at 1, 3, 6, and 12 hours, and 1, 2, 3, 5, 7, 10, 14, 18, 22, 26, and 30 days. The eluent was stored at -70 degrees C until assayed within 2 weeks by microbiological assay (gentamicin and amikacin) or capillary electrophoresis (ceftiofur). RESULTS: Rate of elution for all beads was greatest within the first 24 hours. Cumulative release of total antibiotic dose from beads over 30 days was significantly greater from HAC than PMMA. Antibiotic elution was directly related to the amount of antibiotic incorporated into the cement. Powdered and liquid forms of gentamicin had similar elution rates from PMMA. Elution of amikacin from PMMA beads was greater when the powdered form was used compared with liquid amikacin. Eluent concentrations of ceftiofur were similar to those of the aminoglycosides during the first 3 to 7 days but then decreased precipitously by comparison. CONCLUSIONS: Elution of antibiotics from HAC was greater than from PMMA. Gentamicin- and amikacin-impregnated PMMA and HAC released bactericidal concentrations of antibiotic for at least 30 days. Ceftiofur-impregnated PMMA or HAC is unlikely to provide long-term bactericidal concentrations. CLINICAL RELEVANCE: Gentamicin and amikacin elute effectively from PMMA and HAC.     

Single-dose pharmacokinetics of cefazolin in bovine synovial fluid after intravenous regional injection

Gagnon, H., Ferguson, J.G., Papich, M.G., Bailey, J.V. Single-dose pharmacokinetics of cefazolin in bovine synovial fluid after intravenous regional injection. J. vet. Pharmacol. Therap. 17, 31–37.
The pharmacokinetic properties of cefazolin in the synovial fluid of the tibiotarsal joint were determined in 10 healthy mature cattle after intravenous regional injection of 2 50 mg cefazolin. A pneumatic tourniquet was positioned proximal to the tibiotarsal joint and the intravenous injection was performed distal to the tourniquet. Synovial fluid concentrations of cefazolin increased in the first 30 mm and fluctuated between 54.7 ± 11.0 g/ml (mean ± SEM) and 73.2 ± 13.2 g/ml in the following 90 min while the tourniquet remained inflated. After tourniquet removal, synovial fluid concentration-time curves followed first-order one-compartment model decay in most of the animals with an elimination half-life of 0.82 h (harmonic mean). Therapeutic concentrations of cefazolin in the synovial fluid of normal joints were reached and this injection technique could be used as an alternative to systemic administration of antibiotics to provide adequate concentrations in a localized area.     

In vitro Elution of Amikacin and Vancomycin from Impregnated Plaster of Paris Beads

Objective: To describe in vitro elution characteristics of amikacin and vancomycin from calcium sulfate hemihydrate 98% (plaster of Paris, POP) beads and characterize eluent inhibition of Staphylococcus spp. Study Design: Experimental study. Methods: POP beads were impregnated with amikacin or vancomycin alone or in combination and then incubated alone or in combination for 84 days at 37°C in plastic tubes containing sterile phosphate‐buffered saline (PBS). Beads containing no antimicrobial served as negative control. Beads were intermittently moved to a new tube containing drug‐free PBS. Antimicrobial was measured in the eluent using a polarized fluorescent immunoassay. Eluent inhibition of Staphylococcus spp. was determined at each time point. Results: Antimicrobial release from beads was characterized by an initial rapid phase then a slower phase. Although antimicrobial release from beads occurred throughout the 84 days, most was in the first 24 hours, except for vancomycin alone. Duration of eluent inhibition of Staphylococcus spp. growth ranged from 0.5 (amikacin alone) to 56 days (vancomycin alone). Control eluent did not inhibit bacterial growth. Conclusions: Amikacin elution from POP beads was rapid, inhibiting growth for <24 hours with or without vancomycin. Vancomycin elution was slower and inhibited growth for 56 days alone or for 5 days with amikacin. Clinical Relevance: Vancomycin‐impregnated beads appear to be reasonable as a therapeutic option whereas amikacin‐impregnated POP beads and amikacin and vancomycin combinations may require further study before considering as a therapeutic option.     

The effect of implanting gentamicin-impregnated polymethylmethacrylate beads in the tarsocrural joint of the horse

OBJECTIVE: To determine the effect of intra-articular gentamicin-impregnated polymethylmethacrylate (PMMA) beads inserted in the equine tarsocrural joint on the synovial fluid, synovial lining, and cartilage, and to determine the peak and sustainable gentamicin concentrations in synovial fluid and plasma. STUDY DESIGN: Pharmacokinetic, cytologic, and histologic study of the effect of gentamicin-impregnated PMMA on normal equine tarsocrural joints. ANIMALS: Five healthy adult horses. METHODS: Gentamicin-impregnated PMMA bead strands (3 strands each of 40 beads, with each strand containing 100 mg gentamicin) were surgically inserted into one radiographically normal tarsocrural joint in 5 horses. Each horse had both joints flushed with 1 L of lactated Ringer's solution before bead administration. Synovial fluid total protein concentration, white blood cell (WBC) count, gentamicin concentration, synovial histology, cartilage integrity, and cartilage glycosaminoglycan (GAG) concentrations were determined. RESULTS: Gentamicin concentration (mean +/- SEM peak concentration, 27.9 +/- 2.27 microg/mL) occurred in the first 24 hours and remained above 2 microg/mL for 9 days. Gentamicin concentrations in control joints and the plasma remained below detectable levels. The synovial fluid WBC count for treated joints was increased compared with control joints for 72 hours, but was similar at day 6. The synovial protein concentration in gentamicin-treated joints remained increased for 21 days. Synovium in treated joints had diffuse synovitis, whereas control joints had less fibrovascular proliferation. Superficial cartilage erosion was present in all treated joints. There was no difference in the GAG content of treated and control joint cartilage. CONCLUSIONS: Short-term implantation of gentamicin (300 mg)-impregnated PMMA beads can provide therapeutic levels of gentamicin (>2 microg/mL) in the normal tarsocrural joint for 9 days; however, gentamicin-impregnated PMMA beads induce synovitis and superficial cartilage erosion. CLINICAL RELEVANCE: Temporary intra-articular administration of antibiotic-impregnated PMMA may be an effective way to treat septic joints that require constant high concentrations of antibiotics.     

Pharmacokinetic Disposition of Cefazolin in Serum and Tissue during Canine Total Hip Replacement

Intraoperative cefazolin concentrations were measured in serum, joint capsule, cancellous bone of the acetabulum, and proximal cancellous bone of the femur in 15 dogs undergoing total hip replacement. Cefazolin (22 mg/kg intravenously [IV]) was administered every hour for three doses. The mean peak serum concentrations (+/- SEM) were 387.79 +/- 27.56 micrograms/mL, 521.71 +/- 28.00 micrograms/mL, and 542.20 +/- 30.91 micrograms/mL, respectively. Mean serum concentrations just before administration of doses 2 and 3 were 51.77 +/- 2.39 micrograms/mL, and 64.84 +/- 3.46 micrograms/mL, respectively. The mean cefazolin concentrations in the joint capsule, cancellous bone of the acetabulum, and cancellous bone of the femur were 34.71 +/- 2.50 micrograms/g, 28.70 +/- 7.40 micrograms/g, and 36.20 +/- 3.80 micrograms/g, respectively. The minimum inhibitory concentration of cefazolin for 90% of the common contaminants (MIC90) in this clinic is less than or equal to 2 micrograms/mL or per gram of tissue. Serum concentrations never fell below 15 times the MIC90 (lowest trough, 35.93 micrograms/mL), and the lowest tissue concentration (6.57 micrograms/mL in cancellous bone from the acetabulum) was still more than 3 times the MIC90. The mean tissue concentration was 15 times the MIC90.     

Pharmacokinetics and bioavailability of cefazolin in horses

The pharmacokinetics and bioavailability of cefazolin given (IV, IM) to horses at the dosage of 11 mg/kg were investigated. The disposition of cefazolin given by IV route was characterized by a rapid disposition phase with a half-life of 5 to 10 minutes and a subsequent slower elimination phase with a half-life of 35 to 46 minutes. The total plasma clearance of cefazolin averaged 5.51 ml/min/kg and was due mainly to renal clearance (5.39 ml/min/kg) of unchanged drug. The volume of distribution at steady-state averaged 188 ml/kg. Plasma protein binding of cefazolin at a concentration of 10 micrograms/ml averaged 8.1 +/- 1.9%. Given by the IM route, cefazolin was rapidly absorbed; the extent of bioavailability was 78.4 +/- 18.8%, and the terminal half-life ranged from 49 to 99 minutes. Thus, cefazolin was extensively absorbed, but was eliminated more slowly than after IV administration.     

In vitro elution of amikacin and ticarcillin from a resorbable, self-setting, fiber reinforced calcium phosphate cement

Objective: To determine in vitro elution characteristics of amikacin and ticarcillin from fiber reinforced calcium phosphate beads (FRCP). Sample Population: Experimental. Methods: FRCP beads with water (A), amikacin (B), ticarcillin/clavulanate (C), or both amikacin and ticarcillin/clavulanate (D) were bathed in mL phosphate‐buffered saline (PBS) at 37°C, 5% CO₂ and 95% room air. PBS was sampled (eluent) and beads were placed in fresh PBS at time points 1 and 8 hours and 1, 2, 3, 4, 5, 6, 7, 10, 12, 14, 18, 21, 25, 28, 35, 42, 49, and 56 days. Antibiotic concentration and antimicrobial activity of eluent against Escherichia coli, Staphylococcus aureus, and Klebsiella pneumoniae were determined. Results: Both antibiotics eluted in a bimodal pattern. Beads with a single antibiotic eluted 20.8 ± 2.5% of amikacin and 29.5 ± 0.8% of ticarcillin over 56 days. Coelution of the antibiotics resulted in a lower proportion (AUC_0–∞) of antibiotics eluted for both amikacin (9.5 ± 0.2%) and ticarcillin (21.7 ± 0.09%). Bioassay of antimicrobial activity of the eluent (t=1, 8, and 24 hours) established reduced antimicrobial activity of amikacin from combination beads (D). Conclusions: FRCP beads with amikacin or ticarcillin/clavulanate, but not the combination, are suitable carriers for wound implantation. Clinical Relevance: Duration before complete resorption of FRCP beads in vivo should be determined before clinical use as a resorbable depot. The results of this study underscore the importance of testing drug combinations, despite success of the combination systemically, before their use in local applications.     

Effects of porcine small intestinal submucosa on elution characteristics of gentamicin-impregnated plaster of Paris

OBJECTIVE: To evaluate effects of small intestinal submucosa (SIS) on elution properties of plaster of Paris (POP). SAMPLE POPULATION: 27 POP cylinders, 27 POP spheres, and 9 polymethylmethacrylate (PMMA) spheres. PROCEDURES: Pellets were loaded with gentamicin (50 mg/g) and divided into 7 groups of 9 beads each: PMMA spheres; POP cylinders coated with 0, 4, or 8 layers of SIS; and POP spheres coated with 0, 4, or 8 layers of SIS. Gentamicin concentration was measured 6, 12, 18, 24, 32, 40, and 48 hours and 3, 4, 5, 7, 14, 21, 28, 35, and 42 days after wrapping. Porosity was evaluated via scanning electron microscopy. Curvature factor of elution curves, total amount of drug released (TDR), time required to reach 50% of total release (TDR(t50)), and number of days with concentrations > or = 1 microg/mL were compared among groups. RESULTS: SIS decreased the curvature factor and increased the TDR(t50) and TDR of POP spheres and cylinders. Curvature factor of the PMMA-release curve remained lower than that for any POP group, but all POP groups wrapped in SIS released more gentamicin than PMMA spheres. Gentamicin concentrations remained > or = 1 microg/mL in SIS-wrapped POP and PMMA groups throughout the study. Wrapping POP in SIS minimized the increase in porosity of pellets. CONCLUSIONS AND CLINICAL RELEVANCE: Wrapping POP with SIS slows the release and increases the amount of gentamicin leaching from spheres and cylinders. All groups wrapped in SIS maintained antimicrobial concentrations greater than the minimum inhibitory concentration of most pathogens.     

Pharmacokinetics of probenecid and the effect of oral probenecid administration on the pharmacokinetics of cefazolin in mares

The pharmacokinetics and bioavailability of probenecid given IV and orally at the dosage level of 10 mg/kg of body weight to mares were investigated. Probenecid given IV was characterized by a rapid disposition phase with a mean half-life of 14.0 minutes and a subsequent slower elimination phase with a mean half-life of 87.8 minutes in 5 of 6 mares. In the remaining mare, a rapid disposition phase was not observed, and the half-life of the elimination phase was slower (172 minutes). The mean residence time of probenecid averaged 116 minutes for all 6 mares and 89.2 minutes for the 5 mares with biphasic disposition. The total plasma clearance of probenecid averaged 1.18 +/- 0.49 ml/min/kg, whereas renal clearance accounted for 42.6 +/- 9.3% of the total clearance. The steady-state volume of distribution of probenecid averaged 116 +/- 28.2 ml/kg. Plasma protein binding of probenecid was extensive, with 99.9% of the drug bound at plasma probenecid concentrations of 10 micrograms/ml. The maximum plasma probenecid concentration after 10 mg/kg orally averaged nearly 30 micrograms/ml. The half-life of probenecid after oral administration was approximately 120 minutes. Oral bioavailability was good with greater than 90% of the dose absorbed. The effect of probenecid on tubular secretion of organic anions was evaluated by determining the pharmacokinetics of IV cefazolin (11 mg/kg) administered alone and 15 minutes after probenecid (10 mg/kg orally). Treatment with probenecid did not affect pharmacokinetic values of cefazolin. This failure of probenecid to alter the pharmacokinetics of cefazolin may be caused by insufficient plasma probenecid concentrations after the oral dose.     

Systemic and tissue chamber fluid platinum concentrations released from cis-diamminedichloroplatinum II-impregnated polymethylmethacrylate in healthy dogs

OBJECTIVES: To determine systemic and local platinum concentrations released from subcutaneously implanted cis-diamminedichloroplatinum (cisplatin) -impregnated polymethylmethacrylate (PMMA) and to evaluate systemic or local adverse reactions. ANIMALS: 6 healthy dogs. PROCEDURE: Cisplatin (20 mg) was inserted into PMMA that was fashioned into cylinders and placed into subcutaneous tissue chambers overlying the thorax (treated site). An empty tissue chamber was placed over the opposite side (control site). Plasma samples were obtained for platinum determination before implantation, at 3, 6, and 12 hours after implantation on day 0, and once daily on days 1, 2, 3, 7, 14, 21, and 29. At similar times on similar days, tissue chamber fluid samples also were obtained for platinum determination. Complete blood count, serum urea nitrogen and creatinine concentration determinations, and urinalyses were performed on days 1, 2, 3, 7, 14, 21, and 29. Complete necropsy was performed at conclusion of the study. RESULTS: Tissue chamber platinum concentrations at the treated site were significantly greater than plasma and control site tissue chamber concentrations on days 2, 3, 7, 10. Mean plasma platinum concentration at 3 (0.735 microg/ml), 6 (0.691 microg/ml), 12 (0.534 microg/ml), 24 (0.131 microg/ml), 48 (0.2 microg/ml), 72 (0.1 microg/ml), and 158 (0.014 microg/ml) hours was significantly greater than pretreatment values (0.0 microg/ml). Plasma platinum concentration 10 days after treatment (0.011 microg/ml) did not significantly differ from pretreatment values. Local or systemic adverse reactions were not apparent. CONCLUSIONS: The route of cisplatin administration was safe. Greater concentration of platinum was released locally relative to plasma concentration for an extended period.     

Effects of temporary cessation of milking following intramammary cefazolin sodium infusion on residual antibiotic in lactating dairy cows

The aims of studies were to estimate the withdrawal period of antibiotic from milk after the intramammary infusion of cefazolin sodium (CEZ) in cows with difficulties in frequent milk discharge due to disease such as teat injury. The period was compared among cows milked twice a day after 150 or 450 mg of CEZ were administered to all quarters (Study 1, 2) and the cows in which milking of front-right quarter was ceased for five days after administration of these infusions to only that quarter (Study 3). In Studies 1 and 2, the median of 17.66 µg/ml and 83.18 µg/ml of CEZ were detected in the samples of first milking after intramammary administration, respectively; however, there was no residual antibiotic by 72 hr in all cows. In Study 3, the median of 1.96 µg/ml of CEZ was detected in the sample after the resumption of milking at 120 hr, and the residual was eliminated by 174 hr. The withdrawal period may be prolonged by the cessation of milking after administration, and the period is the total time from cessation to 72 hr after the resumption of milking.     

Pharmacokinetics of enrofloxacin after intravenous,intramuscular and oral administration in houbara bustard (Chlamydotis undulata macqueenii)

The in-vitro activity of enrofloxacin against 117 strains of bacteria isolated from bustards was determined. Minimum inhibitory concentrations for 72% of the Proteus spp., E. coli, Salmonella spp. and Klebsiella spp. (n = 61) and for 48% of the Streptococci spp. and Staphylococci spp. (n = 31) were 0.5 μ g/mL. The minimum inhibitory concentration (MIC) of 76% of Pseudomonas spp. (n = 25) was 2 μg/mL. Fourteen strains were resistant to concentrations 128 μg/mL. The elimination half-lives (t½ elim β) (mean± SEM) of 10 mg/kg enrofloxacin in eight houbara bustards (Chlamydotis undulata) were 6.80± 0.79, 6.39± 1.49 and 5.63± 0.54 h after oral (p.o.), intramuscular (i.m.) and intravenous (i.v.) administration, respectively. Enrofloxacin was rapidly absorbed from the bustard gastro-intestinal tract and maximum plasma concentrations of 1.84± 0.16 μg/mL were achieved after 0.66± 0.05 h. Maximum plasma concentration after i.m. administration of 10 mg/kg was 2.75± 0.11 μg/mL at 1.72± 0.19 h. Maximum plasma concentration after i.m. administration of 15 mg/kg in two birds was 4.86 μg/mL. Bioavailability was 97.3± 13.7% and 62.7± 11.1% after i.m. and oral administration, respectively. Plasma concentrations of enrofloxacin 0.5 μg/mL were maintained for at least 12 h for all routes at 10 mg/kg and for 24 h after i.m. administration at 15 mg/kg. Plasma enrofloxacin concentrations were monitored during the first 3 days of treatment in five houbara bustards and kori bustards (Ardeotis kori) with bacterial infections receiving a single daily i.m. injection of 10 mg/kg for 3 days. The mean plasma enrofloxacin concentrations in the clinical cases at 27 and 51 h (3.69 and 3.86 μg/mL) and at 48 h (0.70 μg/mL) were significantly higher compared with the 3 h and 24 h time intervals from clinically normal birds. The maximum plasma concentration (C_max)/MIC ratio was ranked i.v. (10/mg/kg) > i.m. (15 mg/kg) > i.m. (10 mg/kg) > oral (10 mg/kg), but it was only higher than 8:1 for i.v and i.m. administrations of enrofloxacin at 10 mg/kg and 15 mg/kg, respectively, against a low MIC (0.5 μg/mL). A dosage regimen of 10 mg/kg repeated every 12 h, or 15 mg/kg repeated every 24 h, would be expected to give blood concentrations above 0.5 μg/mL and hence provide therapeutic response in the bustard against a wide range of bacterial infections.     

Single dose pharmacokinetics of terbinafine in cats

The pharmacokinetics of terbinafine was studied in six healthy fasted cats following a single intravenous and oral administration at a dose of 10 mg/kg and 30 mg/kg, respectively, according to a two-period crossover design. Plasma terbinafine concentrations were determined using a reverse phase liquid chromatographic method. The pharmacokinetic parameters were calculated by non-compartmental analysis with WinNonlin 5.2.1 software. After intravenous administration, the terminal half-life and area under the curve from time 0 to infinity were 10.40 ± 4.56 h, 15.20 ± 3.61 h·μg/ml, respectively. After oral dosing, the mean maximum concentration was 3.22 ± 0.60 μg/ml, reached at 1.33 ± 0.41 h. The terminal half-life, area under the curve from time 0 to infinity and apparent volume of distribution were 8.01 ± 3.46 h, 13.77 ± 4.99 h·μg/ml, 25.63 ± 6.29 l/kg, respectively. The absolute bioavailability of terbinafine hydrochloride tablets after oral administration was 31.00 ± 10.85%. Although bioavailability was low, excellent penetration at the site of infection and low minimum inhibitory concentrations values provided terbinafine with good efficacy against dermatophyte infections.     

Clinical application of tobramycin-impregnated calcium sulfate beads in six dogs (2002-2004)

Medical records for six dogs treated with tobramycin-impregnated calcium sulfate beads were reviewed for indications, duration of disease, number of beads implanted, complications, radiographic appearance of the beads, and outcomes. Beads were no longer visible on radiographs made 5 weeks after implantation. Osteomyelitis resolved in five of five dogs with follow-up. The lack of complications and the resolution of clinical signs associated with tobramycin calcium sulfate bead implantation support their clinical application in treating osteomyelitis.     

Residue depletion of thiamphenicol in the sea-bass

The residue depletion of thiamphenicol (TAP) was investigated in the sea-bass (Dicentrarchus labrax) after 5 days' treatment with medicated food at a dose of 15 or 30 mg/kg bw/day. Fish were sampled for blood and muscle + skin from 3 h until 14 days after treatment. Thiamphenicol concentrations were assayed by high performance liquid chromatography. Thiamphenicol concentrations measured 3 h after stopping treatment were 0.77 microg/mL and 0.91 (15 mg/kg dose) or 1.32 microg/mL and 1.47 microg/g (30 mg/kg dose), in plasma and muscle + skin, respectively. After a withdrawal of 3 days, plasma and tissue concentrations were: 0.08 microg/mL and 0.03 microg/g (lower dose) or 0.12 microg/mL and 0.06 microg/g (higher dose), respectively. Thiamphenicol was not detectable either in plasma or in tissues on days 7, 10 and 14 following withdrawal of the medicated food. Based on maximum residue levels (MRL) for TAP in fin fish, established at 50 microg/kg for muscle and skin in natural proportions, a withdrawal period of 5 and 6 days is proposed, after treatment at 15 or 30 mg/kg of TAP with medicated feed pellets, respectively, to avoid the presence of violative residues in the edible tissues of the sea-bass.     

Clinical efficacy of local administration of ceftiofur in a Staphylococcus aureus infection in tissue cages in ponies

Ceftiofur concentrations in an infected and uninfected environment were compared and the efficacy of locally administered ceftiofur was evaluated in an experimental infection with Staphylococcus aureus in tissue cages. Eight ponies had tissue cages (TCs) implanted s.c. on each side of the neck. Into one of the cages 150 mg of ceftiofur was administered and fluid samples were taken to determine ceftiofur concentrations. After 1 week the other TC was infected with S. aureus and subsequently treated with 150 mg ceftiofur administered locally into the TC once daily for 21 days. Samples of fluid were taken to determine ceftiofur concentrations and for bacterial counts. Ceftiofur concentrations did not differ significantly in the infected and uninfected environments after single dose of 150 mg of ceftiofur. Concentrations were considerably in excess of the minimum inhibitory concentration (MIC) of the S. aureus strain used. A marked decrease of viable bacteria in tissue cage fluid (TCF) occurred. In five of seven ponies; however, the infection was not eliminated and abscess formation occurred. Therefore, local application of ceftiofur alone is not advisable for infections with S. aureus in secluded sites in horses, but should be used only with adjunctive therapy.