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1.
Oral bioavailability and pharmacokinetic behaviour of clindamycin in dogs was investigated following intravenous (IV) and oral (capsules) administration of clindamycin hydrochloride, at the dose of 11 mg/kg BW. The absorption after oral administration was fast, with a mean absorption time (MAT) of 0.87+/-0.40 h, and bioavailability was 72.55+/-9.86%. Total clearance (CL) of clindamycin was low, after both IV and oral administration (0.503+/-0.095 vs. 0.458+/-0.087 L/h/kg). Volume of distribution at steady-state (IV) was 2.48+/-0.48 L/kg, indicating a wide distribution of clindamycin in body fluids and tissues. Elimination half-lives were similar for both routes of administration (4.37+/-1.20 h for IV, vs. 4.37+/-0.73 h for oral). Serum clindamycin concentrations following administration of capsules remained above the MICs of very susceptible microorganisms (0.04-0.5 microg/mL) for 12 or 10 h, respectively. Time above the mean inhibitory concentration (MIC) is considered as the index predicting the efficacy of clindamycin (T(>MIC) must be at least 40-50% of the dosing interval), so a once-daily oral administration of 11 mg/kg BW of clindamycin can be considered therapeutically effective. For less susceptible bacteria (with MICs of 0.5-2 microg/mL) the same dose should be given but twice daily.  相似文献   

2.
Posttraumatic osteomyelitis attributable to Staphylococcus aureus infection was experimentally induced in 30 dogs, after which the dogs were treated with clindamycin at various dosage regimens. Of the regimens evaluated, oral administration of 11 mg of clindamycin/kg of body weight twice daily for 28 days was the most effective treatment for the osteomyelitis.  相似文献   

3.
Enrofloxacin was administered orally to 6 healthy dogs at dosages of approximately 2.75, 5.5, and 11 mg/kg of body weight, every 12 hours for 4 days, with a 4-week interval between dosage regimens. Serum and tissue cage fluid (TCF) concentrations of enrofloxacin were measured after the first and seventh treatments. The mean peak serum concentration occurred between 1 and 2.5 hours after dosing. Peak serum concentrations increased with increases in dosage. For each dosage regimen, there was an accumulation of enrofloxacin between the first and seventh treatment, as demonstrated by a significant (P = 0.001) increase in peak serum concentrations. The serum elimination half-life increased from 3.39 hours for the 2.75 mg/kg dosage to 4.94 hours for the 11 mg/kg dosage. Enrofloxacin accumulated slowly into TCF, with peak concentrations being approximately 58% of those of serum. The time of peak TCF concentrations occurred between 3.8 hours and 5.9 hours after drug administration, depending on the dosage and whether it was after single or multiple administrations. Compared with serum concentrations (area under the curve TCF/area under the curve serum), the percentage of enrofloxacin penetration into TCF was 85% at a dosage of 2.75 mg/kg, 83% at a dosage of 5.5 mg/kg, and 88% at a dosage of 11 mg/kg. All 3 dosage regimens of enrofloxacin induced continuous serum and TCF concentrations greater than the minimal concentration required to inhibit 90% (MIC90) of the aerobic and facultative anaerobic clinical isolates tested, except Pseudomonas aeruginosa.(ABSTRACT TRUNCATED AT 250 WORDS)  相似文献   

4.
1. The pharmacokinetics of sparfloxacin in broiler chicken was investigated following a single intravenous dose of 10 mg/kg and a single oral dose of 20 mg/kg. The pharmacokinetic parameters (AUC(0-24) or C(max)) were integrated with the pharmacodynamic parameter (MIC(90)) to optimize sparfloxacin dosage in chicken. 2. The apparent volume of distribution, total body clearance, mean residence time and elimination half-life following oral administration were 2.411/kg, 4.55 ml/min per kg, 10.54 and 5.94 h, respectively. Oral bioavailability was 61.7%. 3. Sparfloxacin was found to possess clinically useful pharmacokinetic properties. Based on pharmacokinetic/pharmacodynamic integration an oral dose of 20 mg/kg sparfloxacin for every 24 h might be recommended for a successful clinical effect in chickens.  相似文献   

5.
Eighteen normal cats were randomly allocated into two blocks with three treatment groups and dosed orally with clindamycin aqueous solution for 10 days at a dosage rate of 5.5 mg/kg twice daily (Group 1), 11 mg/kg twice daily (Group 2), or 22 mg/kg once daily (Group 3). At the end of dosing, all cats were killed and tissues were taken for clindamycin concentration analysis. Clindamycin was extracted from tissues using solid-phase extraction columns followed by microbiological assay of clindamycin using a cylinder plate assay using M. luteus. Recovery from each tissue was determined by inoculating known concentrations of clindamycin into drug-naive tissues and comparing the observed concentration from the expected concentration. Confirmation that the bioassay detected clindamycin and not N-desmethylclindamycin, its active metabolite, was done using gas-chromatography-mass-spectrometry. Concentrations were highest in the lung, with tissue:serum ratios greater than 3 in all groups. Concentrations were higher in Group 3 than Group 1 (P less than 0.05). Only liver concentrations in Group 3 were statistically higher than in Group 2, although all tissues except bone marrow and CSF had numerically higher concentrations in Group 3 than Group 2. The tissue:serum ratio was greater than 1 in all tissues studied except bone, cerebrospinal fluid, brain, and skeletal muscle.  相似文献   

6.
Norfloxacin, a 4-quinolone antibiotic, was administered orally to 4 healthy dogs at dosages of 11 and 22 mg/kg of body weight, every 12 hours for 4 days, with a 4-week interval between dosing regimens. Serum and tissue cage fluid (TCF) norfloxacin concentrations were measured at 0, 0.5, 1, 1.5, 2, 3, 4, 5, 6, 8, 10, and 12 hours after the first and seventh dose of each dosing regimen. When administered at a dosage of 11 mg/kg, the mean peak serum concentration (Cmax) was 1.0 microgram/ml at 1 hour, the time of mean peak concentration (Tmax) after the first dose. After the seventh dose, the Cmax was 1.4 micrograms/ml at Tmax of 1.5 hours. The Tmax for the TCF concentration was 5 hours, with Cmax of 0.3 microgram/ml and 0.7 microgram/ml after the first and seventh dose, respectively. When administered at a dosage of 22 mg/kg, the serum Tmax was 2 hours after the first dose, with Cmax of 2.8 micrograms/ml. After the seventh dose, the serum Tmax was 1.5 hours, with Cmax of 2.8 micrograms/ml. The Tmax for the TCF concentration was 5 hours after the first and seventh doses, with Cmax of 1.2 micrograms/ml and 1.6 micrograms/ml, respectively. After the seventh dose, the serum elimination half-life was 6.3 hours for a dosage of 11 mg/kg and was 6.7 hours for a dosage of 22 mg/kg. For serum concentration, the area under the curve from 0 to 12 hours (AUC0----12) was 8.77 micrograms.h/ml and 18.27 micrograms.h/ml for dosages of 11 mg/kg and 22 mg/kg, respectively.(ABSTRACT TRUNCATED AT 250 WORDS)  相似文献   

7.
沙拉沙星对实验性猪链球菌病及猪水肿病的药效学   总被引：1，自引：0，他引：1  
将兽医专用氟喹诺酮类药物沙拉沙星以不同治疗方案分别对实验性猪链球菌病和猪水肿病进行药效学研究。在每天总剂量相同的情况下 ,每天 1次与每天 2次给药取得了较好而相似的疗效 (P>0 .0 5 ) :对猪链球菌病 ,每天总剂量为 10 m g/ kg时 ,肌注给药的治愈率分别为 10 0 %和 90 %,但在迅速改善临床症状方面 ,每天 1次给药优于每天 2次(P<0 .0 5 ) ;对猪水肿病 ,每天总剂量为 5 mg/ kg时 ,肌注给药的治愈率均为 10 0 %。结果表明 ,在总剂量相同时 ,以大剂量、长间隔与以较小剂量、短间隔治疗实验性猪链球菌病与猪水肿病 ,均取得相当的疗效。  相似文献   

8.
The tarsocrural joints of 11 horses were inoculated with 1.2 to 2.16 x 10(6) viable Staphylococcus aureus organisms susceptible to a trimethoprim-sulfadiazine (TMP-SDZ) combination with minimal inhibitory concentration (MIC) of 0.25 micrograms of TMP/ml and 4.75 micrograms of SDZ/ml. Antimicrobial treatment consisted of oral administration of a TMP-SDZ combination--30 mg/kg of body weight given once daily (group-1 horses) or 60 mg/kg given as 30 mg/kg every 12 hours (group-2 horses). Paired serum and synovial fluid samples were obtained before intra-articular inoculation with the S aureus, after inoculation with S aureus but before antimicrobial treatment, and after inoculation at various hourly intervals after oral administration of the TMP-SDZ combination. The TMP-SDZ combination was administered daily in the 2 dosages for 21 days. Samples were collected after day 3 of repetitive drug administration so that drug steady-state concentration would have been achieved. Serum and synovial fluid samples were analyzed for TMP and SDZ concentrations. Administration of the TMP-SDZ combination at a dosage of 30 mg/kg once daily was not effective in maintaining TMP or SDZ concentrations above the MIC of TMP-SDZ for the S aureus (0.25 and 4.75 micrograms/ml for TMP and SDZ, respectively) in the infected synovial fluid or in maintaining adequate TMP concentration in the serum. The alternative use of the TMP-SDZ combination at a dosage of 60 mg/kg given as 30 mg/kg every 12 hours was effective in maintaining serum and synovial fluid concentrations of TMP and SDZ that were greater than the MIC for the infective organism.(ABSTRACT TRUNCATED AT 250 WORDS)  相似文献   

9.
The theory of a time-dependent effect of amoxycillin was examined in a model of porcine Actinobacillus pleuropneumoniae (Ap)-infection using clinically relevant dosage regimens. Twenty hours after infection of fourteen pigs, when clinical signs of pneumonia were present, one group of pigs received a single dose of amoxycillin (20 mg/kg, i.m.), whereas another group received four doses of 5 mg/kg injected at 8-h intervals. A similar AUC of the plasma amoxycillin concentration versus time curve was obtained in the two groups, whereas the maximum concentration was threefold higher using the single high dose. Plasma amoxycillin was above the MIC for twice as long using the fractionated dosage scheme. The condition of the animals was evaluated by clinical and haematological observations combined with quantification of biochemical infection markers: C-reactive protein, zinc and ascorbic acid. Within 48 h of treatment, the pigs in both treatment groups recovered clinically. No significant differences in the time-course of clinical observations or plasma concentrations of the biomarkers of infection were observed between the two treatments. In conclusion, the efficacy of these two dosage regimens of amoxycillin was not significantly different in treatment of acute Ap-infection in pigs.  相似文献   

10.
In a four-period, cross-over study, the fluoroquinolone antibacterial drug marbofloxacin (MB) was administered to calves, alone and in combination with the nonsteroidal anti-inflammatory drug tolfenamic acid (TA). Both drugs were administered intramuscularly (IM) at doses of 2 mg/kg. A tissue cage model of inflammation, based on the actions of the mild irritant carrageenan, was used to evaluate the pharmacokinetics (PK) of MB and MB in combination with TA. MB mean values of area under concentration-time curve (AUC) were 15.1 μg·h/mL for serum, 12.1 μg·h/mL for inflamed tissue cage fluid (exudate) and 9.6 μg·h/mL for noninflamed tissue cage fluid (transudate). Values of C(max) were 1.84, 0.35 and 0.31 μg/mL, respectively, for serum, exudate and transudate. Mean residence time (MRT) of 23.6 h (exudate) and 22.6 h (transudate) also differed significantly from serum MRT (8.6 h). Co-administration of TA did not affect the PK profile of MB. The pharmacodynamics of MB was investigated using a bovine strain of Mannheimia haemolytica. Time-kill curves were established ex vivo on serum, exudate and transudate samples. Modelling the ex vivo serum time-kill data to the sigmoid E(max) equation provided AUC(24 h) /MIC values required for bacteriostatic (18.3 h) and bactericidal actions (92 h) of MB and for virtual eradication of the organism was 139 h. Corresponding values for MB + TA were 20.1, 69 and 106 h. These data were used to predict once daily dosage schedules for a bactericidal action, assuming a MIC(90) value of 0.24 μg/mL, a dose of 2.6 mg/kg for MB and 2.19 mg/kg for MB + TA were determined, which are similar to the currently recommended dose of 2.0 mg/kg.  相似文献   

11.
Oral clindamycin disposition after single and multiple doses in normal cats   总被引：1，自引：0，他引：1  
Eighteen normal cats were randomly allocated into three treatment groups and dosed with clindamycin aqueous solution for 10 days at a dosage rate of: (1) 5.5 mg/kg b.i.d.; (2) 11 mg/kg b.i.d.; or (3) 22 mg/kg once daily. Serum disposition of clindamycin was determined after the first and last dose of clindamycin was given, and was analyzed using model-independent pharmacokinetics by both the trapezoidal rule method and the predictive equation method. Complete blood counts and clinical chemistries were determined before and after the study. The trapezoidal rule method produced similar mean results with much less variance than the predictive equation method. Mean residence time was longer (P less than 0.05) after the high dose (393 +/- 77 min) than after either the low or medium doses (276 +/- 51 and 274 +/- 45 min, respectively). Oral volume of distribution (Vd(ss)/F) after the high dose (3.06 +/- 0.92 l/kg) was larger (P less than 0.05) than that after the low or medium doses (1.62 +/- 0.30 and 1.76 +/- 0.53 l/kg, respectively). Oral Vd(ss)/F was significantly smaller (P less than 0.001) after the last dose than after the first dose when analyzed by treatment group. Significant (P less than 0.01) decreases in the leukogram and erythrogram were observed, due to the large amount of blood collected for drug analysis. No clinical signs of drug intoxication were observed, and no drug-related necropsy findings were found.  相似文献   

12.
OBJECTIVE: To evaluate pharmacokinetics of once daily i.v. administration of gentamicin sulfate to adult horses that had abdominal surgery. DESIGN: Prospective study. ANIMALS: 28 adult horses that underwent abdominal surgery for colic. PROCEDURE: 14 horses were treated with each dosage of gentamicin (i.e., 6.6 or 4 mg/kg, i.v., q 24 h) and blood samples were collected for pharmacokinetic analysis. Plasma gentamicin concentrations were measured by use of a fluorescence polarization immunoassay. Pharmacokinetic analysis measured the elimination half-life, volume of distribution, and gentamicin total systemic clearance. Treatment outcome, CBC, and serum creatinine concentrations were recorded. RESULTS: 1 horse in the high-dosage group died. All other horses successfully recovered, and did not develop bacterial infection or have evidence of drug toxicosis resulting in renal injury. Mean pharmacokinetic variables for gentamicin administration at a high or low dosage (i.e., 6.6 or 4 mg/kg, i.v., q 24 h) were half-life of 1.47 and 1.61 hours, volume of distribution of 0.17 and 0.17 L/kg, and systemic clearance of 1.27 and 1.2 ml/kg/min, respectively. Mean serum creatinine concentration was 1.74 and 1.71 for the high and low dosages, respectively, and serum creatinine concentration was not correlated with gentamicin clearance. CONCLUSIONS AND CLINICAL RELEVANCE: Gentamicin administration at a dosage of 4 mg/kg, i.v., every 24 hours, will result in plasma concentrations that are adequate against susceptible bacteria with a minimum inhibitory concentration (MIC) of < or = 2.0 micrograms/ml. Gentamicin administration at a calculated dosage of 6.8 mg/kg, i.v., every 24 hours will result in optimum plasma concentrations against susceptible bacteria with a MIC of < or = 4.0 micrograms/ml.  相似文献   

13.
The pharmacokinetics and pharmacodynamics of danofloxacin were studied in the camel in a two period cross-over study. After intravenous (i.v.) administration at a dose rate of 1.25 mg/kg, the pharmacokinetics of danofloxacin indicated a high volume of distribution (V(d(area))=3.43 L/kg), relatively rapid clearance (0.44 L/kg/h) and half-life of 5.37 h. After intramuscular (i.m.) dosing absorption was complete (F=114.5) and rapid (T((1/2)abs)=0.12 h) and terminal half-life was 5.71 h. Danofloxacin penetrated fairly slowly into both inflamed (exudate) and non-inflamed (transudate) tissue cage fluids and was cleared slowly from these fluids, elimination half-life being at least twice that for serum for both exudate and transudate after both i.v. and i.m. dosing. The antibacterial actions of danofloxacin against the camel pathogen Escherichia coli 0157-H7 were determined by measurement of minimum inhibitory concentration (MIC) in vitro (single measurement) and ex vivo measurements of bacterial count at nine times between one and 48 h after i.m. dosing in each of the fluids, serum, exudate, and transudate. Using in vitro MIC data and in vivo pharmacokinetic parameters, the surrogate markers of antimicrobial activity, C(max)/MIC, AUC/MIC and T>MIC, were determined for all three fluids. The ex vivo serum AUC(24 h)/MIC data were integrated with reduction in bacterial count to provide values producing a bacteriostatic action (no change in bacterial count), inhibition of bacterial count by 50%, reduction in bacterial count by 99.9% (bactericidal action) and elimination of bacteria. Mean AUC(24h)/MIC values were 17.20, 20.07, 21.24, and 68.37 h, respectively. To describe the latter, the introduction of a new term to supplement MIC and minimum bactericidal concentration (MBC) is proposed, namely minimum elimination concentration (MEC). A novel means of designing antimicrobial drug dosage schedules for evaluation in clinical trials is proposed, using ex vivo AUC(24h)/MIC values for bactericidal activity and elimination of bacteria together with MIC(90) data for camel pathogens.  相似文献   

14.
Pharmacokinetics of marbofloxacin in horses   总被引：3，自引：0，他引：3  
Marbofloxacin is a fluoroquinolone antibiotic expected to be effective in the treatment of infections involving gram-negative and some gram-positive bacteria in horses. In order to design a rational dosage regimen for the substance in horses, the pharmacokinetic properties of marbofloxacin were investigated in 6 horses after i.v., subcutaneous and oral administration of a single dose of 2 mg/kg bwt and the minimal inhibitory concentrations (MIC) assessed for bacteria isolated from equine infectious pathologies. The clearance of marbofloxacin was mean +/- s.d. 0.25 +/- 0.05 l/kg/h and the terminal half-life 756 +/- 1.99 h. The marbofloxacin absolute bioavailabilities after subcutaneous and oral administration were 98 +/- 11% and 62 +/- 8%, respectively. The MIC required to inhibit 90% of isolates (MIC90) was 0.027 microg/ml for enterobacteriaceae and 0.21 microg/ml for Staphylococcus aureus. The values of surrogate markers of antimicrobial efficacy (AUIC, Cmax/MIC ratio, time above MIC90) were calculated and the marbofloxacin concentration profiles simulated for repeated administrations. These data were used to determine rational dosage regimens for target bacteria. Considering the breakpoint values of efficacy indices for fluoroquinolones, a marbofloxacin dosage regimen of 2 mg/kg bwt/24 h by i.v., subcutaneous or oral routes was more appropriate for enterobacteriaceae than for S. aureus.  相似文献   

15.
The purpose of this study was to investigate the pharmacokinetic characteristics of amoxicillin (AMX) trihydrate in male Asian elephants, Elephas maximus, following intramuscular administration at two dosages of 5.5 and 11 mg/kg body weight (b.w.). Blood samples were collected from 0.5 up to 72 h. The concentration of AMX in elephant plasma was measured using liquid chromatography electrospray ionization mass spectrometry. AMX was measurable up to 24 h after administration at two dosages. Peak plasma concentration (Cmax) was 1.20 ± 0.39 μg/mL after i.m. administration at a dosage of 5.5 mg/kg b.w., whereas it was 3.40 ± 0.63 μg/mL at a dosage of 11 mg/kg b.w. A noncompartment model was developed to describe the disposition of AMX in Asian elephants. Based on the preliminary findings found in this research, the dosage of 5.5 and 11 mg/kg b.w. produced drug plasma concentrations higher than 0.25 mg/mL for 24 h after i.m. administration. Thereafter, i.m. administration with AMX at a dosage of 5.5 mg/kg b.w. appeared a more suitable dose than 11 mg/kg b.w. However, more studies are needed to determine AMX clinical effectiveness in elephants.  相似文献   

16.
The effects of different doses and dosage regimens on gentamicin pharmacokinetics and tissue residues were determined. Five groups of 12 sheep each were given gentamicin IM: group I, 2 mg of gentamicin sulfate/kg once; group II, 6 mg/kg once; group III, 18 mg/kg once; group IV, 6 mg/kg every 24 hours for 3 doses; and group V, 2 mg/kg every 8 hours for 9 doses. Serum concentrations were determined serially until sheep were killed and necropsied. Three sheep from each group were killed at 1, 4, 8, and 12 days after the last dose was administered. Renal cortex, renal medulla, liver, spleen, lung, skeletal muscle, and skeletal muscle at the injection site were assayed for gentamicin. An exponential equation was fitted to the serum concentrations, and various pharmacokinetic variables were determined. Serum clearance tended to increase as the single dose increased (P = 0.0588). Steady-state volume of distribution increased as the single dose was increased (P less than 0.05). Renal cortex contained the highest concentration of gentamicin which decreased in a biexponential manner. Concentrations in all tissues, except the injection site, were dependent upon the amount of the total dose, not the size of the injected dose (P less than 0.05). Concentrations at the injection site were up to 29 micrograms/g of tissue at 1 day after the last dose was given and were dependent upon the amount of total dose from multiple injections, not on the amount of each injected dose (P less than 0.05).(ABSTRACT TRUNCATED AT 250 WORDS)  相似文献   

17.
Ciprofloxacin, a fluoroquinolone antimicrobial agent, was administered orally to 4 healthy dogs at dosage of approximately 11 and 23 mg/kg of body weight, every 12 hours for 4 days, with a 4-week interval between dosing regimens. Serum and tissue cage fluid (TCF) concentrations of ciprofloxacin were measured after the first and seventh dose of each dosing regimen. The peak concentration was greatest in the serum after multiple doses of 23 mg/kg (mean +/- SEM; 5.68 +/- 0.54 micrograms/ml) and least in the TCF after a single dose of 11 mg/kg (0.43 +/- 0.54 micrograms/ml). The time to peak concentration was not influenced by multiple dosing or drug dose, but was longer for TCF (6.41 +/- 0.52 hour) than for serum (1.53 +/- 0.52 hour). Accumulation of ciprofloxacin was reflected by the area under the concentration curve from 0 to 12 hours after administration (AUC0----12). The AUC0----12 was greatest in the serum after multiple doses of 23 mg/kg (31.95 +/- 1.90 micrograms.h/ml) and least in the TCF after a single dose of 11 mg/kg (3.87 +/- 1.90 micrograms.h/ml). The elimination half-life was not influenced by multiple dosing or dose concentration, but was greater for TCF (14.59 +/- 1.91 hours) than for serum (5.14 +/- 1.91 hours). The percentage of TCF penetration (AUCTCF/AUCserum) was greater after multiple doses (95.76 +/- 6.79%) than after a single dose (55.55 +/- 6.79%) and was not different between doses of 11 and 23 mg/kg. Both dosing regimens of ciprofloxacin resulted in continuous serum and TCF concentrations greater than 90% of the minimal inhibitory concentration for the aerobic and facultative anaerobic clinical isolates tested, including Pseudomonas aeruginosa.  相似文献   

18.
Vallé, M., Schneider, M., Galland, D., Giboin, H., Woehrlé, F. Pharmacokinetic and pharmacodynamic testing of marbofloxacin administered as a single injection for the treatment of bovine respiratory disease. J. vet. Pharmacol. Therap. 35, 519–528. New approaches in Pharmacokinetic/Pharmacodynamic (PK/PD) integration suggested that marbofloxacin, a fluoroquinolone already licensed for the treatment of bovine respiratory disease at a daily dosage of 2 mg/kg for 3–5 days, would be equally clinically effective at 10 mg/kg once (Forcyl®), whilst also reducing the risk of resistance. This marbofloxacin dosage regimen was studied using mutant prevention concentration (MPC), PK simulation, PK/PD integration and an in vitro dynamic system. This system simulated the concentration–time profile of marbofloxacin in bovine plasma established in vivo after a single 10 mg/kg intramuscular dose and killing curves of field isolated Pasteurellaceae strains of high (minimum inhibitory concentration (MIC) MIC ≤0.03 μg/mL), average (MIC of 0.12–0.25 μg/mL) and low (MIC of 1 μg/mL) susceptibility to marbofloxacin. The marbofloxacin MPC values were 2‐ to 4‐fold the MIC values for all Mannheimia haemolytica, Pasteurella multocida tested. Marbofloxacin demonstrated a concentration‐dependant killing profile with bactericidal activity observed within 1 h for most strains. No resistance development (MIC ≥4 μg/mL) was detected in the dynamic tests. Target values for risk of resistance PK/PD surrogates (area under the curve (AUC) AUC24 h/MPC and T>MPC/TMSW ratio) were achieved for all clinically susceptible pathogens. The new proposed dosing regimen was validated in vitro and by PK/PD integration confirming the single‐injection short‐acting antibiotic concept.  相似文献   

19.
OBJECTIVE: To determine the pharmacokinetics of potassium bromide (KBr) in horses after single and multiple oral doses. ANIMALS: Twelve adult Standardbred and Thoroughbred mares. PROCEDURE: Horses were randomly assigned to two treatment groups. Group 1 horses were given a single oral dose of 120 mg/kg potassium bromide. Part 2 of the study evaluated a loading dose of 120 mg/kg KBr daily by stomach tube for 5 days, followed by 40 mg/kg daily in feed for 7 days. Serum concentrations of KBr were measured to construct concentration versus time curves and to calculate pharmacokinetic parameters. Treated horses were monitored twice daily by clinical examination. Serum concentrations of sodium, potassium and chloride ions and partial pressures of venous blood gases were determined. RESULTS: Maximum mean serum concentration following a single dose of KBr (120 mg/kg) was 423 +/- 22 microg/mL and the mean elimination half-life was 75 +/- 14 h. Repeated administration of a loading dose of KBr (120 mg/kg once daily for 5 d) gave a maximum serum concentration 1639 +/- 156 microg/mL. The administration of lower, maintenance doses (40 mg/kg once daily) was associated with decreased serum bromide concentrations, which plateaued at approximately 1000 microg/mL. Administration of KBr was associated with significant but transient changes in serum potassium and sodium concentrations, and possible changes in base excess and plasma bicarbonate concentrations. High serum concentrations of bromide were associated with an apparent increase in serum chloride concentrations, when measured on an ion specific electrode. CONCLUSIONS: and clinical relevance Loading doses of 120 mg/kg daily over 5 d and maintenance doses of approximately 90 mg/kg of KBr administered once daily resulted in serum bromide concentrations consistent with therapeutic efficacy for the management of seizures in other species. The clinical efficacy of this agent as an anticonvulsant medication and/or calmative in horses warrants further investigation.  相似文献   

20.
Sodium cefadroxil was administered as a single intravenous dose (25 mg/kg) to six healthy adult mares. Plasma samples were collected over a 24-h period and cefadroxil concentrations were measured by microbiological assay. The pharmacokinetic behavior of the drug was appropriately described in terms of a one-compartment open model. Values for the major pharmacokinetic terms were: extrapolated initial plasma concentration = 59.2 +/- 15.0 micrograms/ml; half-life = 46 +/- 20 min; apparent volume of distribution = 462 +/- 191 ml/kg; and body clearance = 7.0 +/- 0.6 ml/min.kg. In a subsequent study, a suspension of cefadroxil monohydrate was administered intragastrically (25 mg/kg) to the same six horses. Plasma concentrations of the drug peaked at 1-2 h but, in general, absorption was both poor and inconsistent. The data were unsuitable for determination of cefadroxil bioavailability from this oral dosage form. Ninety-nine isolates of eleven bacterial species obtained from clinically ill horses were tested for susceptibility to cefadroxil. All strains of Streptococcus equi, Streptococcus zooepidemicus, coagulase-positive staphylococci, Corynebacterium pseudotuberculosis and five out of six strains of Actinobacillus suis were highly susceptible to the drug (MIC less than 4 micrograms/ml). Escherichia coli, Klebsiella pneumoniae and Salmonella sp. showed intermediate susceptibility (MIC 4-16 micrograms/ml), while all isolates of Corynebacterium (Rhodococcus) equi, Enterobacter cloacae and Pseudomonas aeruginosa proved to be highly resistant to cefadroxil (MIC greater than 128 micrograms/ml).  相似文献   

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