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1.
J Vet Pharmacol Ther ; 39(1): 40-4, 2016 Feb.
Article in English | MEDLINE | ID: mdl-25982523

ABSTRACT

Cefuroxime pharmacokinetic profile was investigated in 6 Beagle dogs after single intravenous, intramuscular, and subcutaneous administration at a dosage of 20 mg/kg. Blood samples were withdrawn at predetermined times over a 12-h period. Cefuroxime plasma concentrations were determined by HPLC. Data were analyzed by compartmental analysis. Peak plasma concentration (Cmax ), time-to-peak plasma concentration (Tmax ), and bioavailability for the intramuscular and subcutaneous administration were (mean ± SD) 22.99 ± 7.87 µg/mL, 0.43 ± 0.20 h, and 79.70 ± 14.43% and 15.37 ± 3.07 µg/mL, 0.99 ± 0.10 h, and 77.22 ± 21.41%, respectively. Elimination half-lives and mean residence time for the intravenous, intramuscular, and subcutaneous administration were 1.12 ± 0.19 h and 1.49 ± 0.21 h; 1.13 ± 0.13 and 1.79 ± 0.24 h; and 1.04 ± 0.23 h and 2.21 ± 0.23 h, respectively. Significant differences were found between routes for Ka , MAT, Cmax , Tmax , t½(a) , and MRT. T > MIC = 50%, considering a MIC of 1 µg/mL, was 11 h for intravenous and intramuscular administration and 12 h for the subcutaneous route. When a MIC of 4 µg/mL is considered, T > MIC = 50% for intramuscular and subcutaneous administration was estimated in 8 h.


Subject(s)
Anti-Bacterial Agents/pharmacokinetics , Cefuroxime/pharmacokinetics , Dogs/blood , Animals , Anti-Bacterial Agents/administration & dosage , Anti-Bacterial Agents/blood , Area Under Curve , Biological Availability , Cefuroxime/administration & dosage , Cefuroxime/blood , Cross-Over Studies , Drug Administration Routes , Female , Half-Life , Male
2.
Vet J ; 205(1): 21-7, 2015 Jul.
Article in English | MEDLINE | ID: mdl-25981931

ABSTRACT

Antimicrobial agents are essential tools for treating and controlling bacterial infections in poultry production. Veterinarians have a huge responsibility when using antimicrobials in poultry producing meat and eggs for human consumption. The term 'judicious use' of antimicrobials implies the optimal selection of drug, dose and duration of antimicrobial treatment, along with a reduction in inappropriate and excessive use as a means of slowing the emergence of antimicrobial resistance. The proper use of antimicrobials depends on the knowledge of interrelationships between bacteria, antimicrobial, host and consumer. This article reviews the anatomical-physiological features of poultry relating to drug disposition as well as the pharmacological and therapeutic characteristics of the most commonly used antimicrobials in broiler chickens. Doses frequently employed for flock treatment are presented as are accepted withdrawal times.


Subject(s)
Anti-Infective Agents/therapeutic use , Chickens , Poultry Diseases/drug therapy , Animals , Humans
3.
J Vet Pharmacol Ther ; 35(6): 534-40, 2012 Dec.
Article in English | MEDLINE | ID: mdl-22132730

ABSTRACT

The pharmacokinetic properties and bone concentrations of lincomycin in cats after single intravenous and intramuscular administrations at a dosage rate of 10 mg/kg were investigated. Lincomycin minimum inhibitory concentration (MIC) for some gram-positive strains isolated from clinical cases was determined. Serum lincomycin disposition was best-fitted to a bicompartmental and a monocompartmental open models with first-order elimination after intravenous and intramuscular dosing, respectively. After intravenous administration, distribution was rapid (T(1/2(d)) = 0.22 ± 0.09 h) and wide as reflected by the volume of distribution (V((d(ss)))) of 1.24 ± 0.08 L/kg. Plasma clearance was 0.28 ± 0.09 L/h · kg and elimination half-life (T(1/2)) 3.56 ± 0.62 h. Peak serum concentration (C(max)), T(max), and bioavailability for the intramuscular administration were 7.97 ± 2.31 µg/mL, 0.12 ± 0.05 h, and 82.55 ± 23.64%, respectively. Thirty to 45 min after intravenous administration, lincomycin bone concentrations were 9.31 ± 1.75 µg/mL. At the same time after intramuscular administration, bone concentrations were 3.53 ± 0.28 µg/mL. The corresponding bone/serum ratios were 0.77 ± 0.04 (intravenous) and 0.69 ± 0.18 (intramuscular). Lincomycin MIC for Staphylococcus spp. ranged from 0.25 to 16 µg/mL and for Streptococcus spp. from 0.25 to 8 µg/mL.


Subject(s)
Anti-Bacterial Agents/administration & dosage , Anti-Bacterial Agents/pharmacokinetics , Bone and Bones/metabolism , Cats/blood , Lincomycin/administration & dosage , Lincomycin/pharmacokinetics , Animals , Anti-Bacterial Agents/blood , Anti-Bacterial Agents/metabolism , Area Under Curve , Biological Availability , Female , Half-Life , Injections, Intramuscular , Injections, Intravenous , Lincomycin/blood , Lincomycin/metabolism , Male
4.
Res Vet Sci ; 91(1): 129-131, 2011 Aug.
Article in English | MEDLINE | ID: mdl-20800248

ABSTRACT

The pharmacokinetic profile and bioavailability of a long-acting formulation of cephalexin after intramuscular administration to cats was investigated. Single intravenous (cephalexin lysine salt) and intramuscular (20% cephalexin monohydrate suspension) were administered to five cats at a dose rate of 10 mg/kg. Serum disposition curves were analyzed by noncompartmental approaches. After intravenous administration, volume of distribution (V(z)), total body clearance (Cl(t)), elimination constant (λ(z)), elimination half-life (t(½)(λ)) and mean residence time (MRT) were: 0.33±0.03 L/kg; 0.14±0.02 L/hkg, 0.42±0.05 h(-1), 1.68±0.20 h and 2.11±0.25 h, respectively. Peak serum concentration (C(max)), time to peak serum concentration (T(max)) and bioavailability after intramuscular administration were 15.67±1.95 µg/mL, 2.00±0.61 h and 83.33±8.74%, respectively.


Subject(s)
Anti-Bacterial Agents/pharmacokinetics , Cephalexin/pharmacokinetics , Animals , Anti-Bacterial Agents/administration & dosage , Anti-Bacterial Agents/blood , Biological Availability , Cats , Cephalexin/administration & dosage , Cephalexin/blood , Delayed-Action Preparations/administration & dosage , Delayed-Action Preparations/pharmacokinetics , Injections, Intramuscular/veterinary , Injections, Intravenous/veterinary
5.
Vet J ; 187(1): 129-32, 2011 Jan.
Article in English | MEDLINE | ID: mdl-19854664

ABSTRACT

The aim of this study was to characterise the pharmacokinetic properties of different formulations of erythromycin in cats. Erythromycin was administered as lactobionate (4 mg/kg intravenously (IV)), base (10mg/kg, intramuscularly (IM)) and ethylsuccinate tablets or suspension (15 mg/kg orally (PO)). After IV administration, the major pharmacokinetic parameters were (mean ± SD): area under the curve (AUC)((0-∞)) 2.61 ± 1.52 microgh/mL; volume of distribution (V(z)) 2.34 ± 1.76L/kg; total body clearance (Cl(t)) 2.1 0 ± 1.37 L/hkg; elimination half-life (t(½)(λ)) 0.75 ± 0.09 h and mean residence time (MRT) 0.88 ± 0.13 h. After IM administration, the principal pharmacokinetic parameters were (mean ± DS): peak concentration (C(max)), 3.54 ± 2.16 microg/mL; time of peak (T(max)), 1.22 ± 0.67 h; t(½)(λ), 1.94 ± 0.21 h and MRT, 3.50 ± 0.82 h. The administration of erythromycin ethylsuccinate (tablets and suspension) did not result in measurable serum concentrations. After IM and IV administrations, erythromycin serum concentrations were above minimum inhibitory concentration (MIC)(90)=0.5 microg/mL for 7 and 1.5h, respectively. However, these results should be interpreted cautiously since tissue erythromycin concentrations have not been measured and can reach much higher concentrations than in blood, which may be associated with enhanced clinical efficacy.


Subject(s)
Anti-Bacterial Agents/administration & dosage , Anti-Bacterial Agents/pharmacokinetics , Erythromycin/administration & dosage , Erythromycin/pharmacokinetics , Administration, Oral , Animals , Anti-Bacterial Agents/blood , Area Under Curve , Cat Diseases/drug therapy , Cats/blood , Erythromycin/blood , Female , Half-Life , Injections, Intramuscular/veterinary , Injections, Intravenous/veterinary , Male , Metabolic Clearance Rate
7.
Vet J ; 180(3): 304-16, 2009 Jun.
Article in English | MEDLINE | ID: mdl-18314361

ABSTRACT

This article reviews the general pharmacological properties of antimicrobial drugs used in feline medicine. It focuses on recent advances in pharmacokinetics, providing an update on indications, drug interactions and adverse reactions or toxicity in the cat. Attention is given to the most used groups, such as cephalosporins and fluoroquinolones, reviewing their basic features and clinical uses, and discusses the pharmacokinetic advantages of the newer members of each group. The older groups (penicillins, aminoglycosides, macrolides and tetracyclines) are also considered with regard to their general features and current uses, and any recent reports on adverse reactions in cats are provided.


Subject(s)
Anti-Bacterial Agents/administration & dosage , Anti-Bacterial Agents/therapeutic use , Bacterial Infections/veterinary , Cat Diseases/drug therapy , Animals , Anti-Bacterial Agents/pharmacokinetics , Bacterial Infections/drug therapy , Cats
8.
J Vet Pharmacol Ther ; 31(6): 496-500, 2008 Dec.
Article in English | MEDLINE | ID: mdl-19000270

ABSTRACT

The purpose of this study was to describe and compare the pharmacokinetic properties of different formulations of erythromycin in dogs. Erythromycin was administered as lactobionate (10 mg/kg, IV), estolate tablets (25 mg/kg p.o.) and ethylsuccinate tablets or suspension (20 mg/kg p.o.). After intravenous (i.v.) administration, the principal pharmacokinetic parameters were (mean +/- SD): AUC((0-infinity)) 4.20 +/- 1.66 microg x h/mL; C(max) 6.64 +/- 1.38 microg/mL; V(z) 4.80 +/- 0.91 L/kg; Cl(t) 2.64 +/- 0.84 L/h.kg; t((1/2)lambda) 1.35 +/- 0.40 h and MRT 1.50 +/- 0.47 h. After the administration of estolate tablets and ethylsuccinate suspension, the principal pharmacokinetic parameters were (mean +/- SD): C(max), 0.30 +/- 0.17 and 0.17 +/- 0.09 microg/mL; t(max), 1.75 +/- 0.76 and 0.69 +/- 0.30 h; t((1/2)lambda), 2.92 +/- 0.79 and 1.53 +/- 1.28 h and MRT, 5.10 +/- 1.12 and 2.56 +/- 1.77 h, respectively. The administration of erythromycin ethylsuccinate tablets did not produce measurable serum concentrations. Only the i.v. administration rendered serum concentrations above MIC(90) = 0.5 microg/mL for 2 h. However, these results should be cautiously interpreted as tissue erythromycin concentrations have not been measured in this study and, it is recognized that they can reach much higher concentrations than in blood, correlating better with clinical efficacy.


Subject(s)
Anti-Bacterial Agents/administration & dosage , Anti-Bacterial Agents/pharmacokinetics , Erythromycin Estolate/administration & dosage , Erythromycin Estolate/pharmacokinetics , Erythromycin Ethylsuccinate/pharmacokinetics , Administration, Oral , Animals , Anti-Bacterial Agents/blood , Area Under Curve , Cross-Over Studies , Dogs , Dosage Forms , Erythromycin Estolate/blood , Erythromycin Ethylsuccinate/administration & dosage , Erythromycin Ethylsuccinate/blood , Female , Half-Life , Injections, Intravenous , Linear Models , Male , Metabolic Clearance Rate
9.
Res Vet Sci ; 85(3): 570-4, 2008 Dec.
Article in English | MEDLINE | ID: mdl-18433809

ABSTRACT

This study describes and compares the pharmacokinetics of a single 7.5mg/kg dose of cephalexin monohydrate oil-based 20% suspension after its administrations to six cows by the intramuscular (i.m.) and subcutaneous (s.c.) routes, and to five calves by the i.m. route. Significantly (P<0.05) higher peak plasma concentrations (5.6+/-0.79microg/ml versus 3.93+/-1.24microg/ml) and lower half-life (1.81+/-0.56h versus 4.21+/-0.82h) and mean residence time (4.12+/-1.07h versus 6.63+/-0.85h) were obtained after i.m. administration when compared to the s.c. administration to cows. No differences were found between pharmacokinetic parameters calculated for cows and calves. Cephalexin plasma concentrations remained above 0.5-0.75microg/ml for 11-14h and 8-9h after the s.c. and i.m. administrations, respectively. Thus, route of administration may be an important issue to be considered when calculating dosage schedules for successful treatments and safe withdrawal times for veterinary medicines.


Subject(s)
Cephalexin/pharmacokinetics , Animals , Anti-Bacterial Agents/administration & dosage , Anti-Bacterial Agents/blood , Anti-Bacterial Agents/pharmacokinetics , Area Under Curve , Cattle , Cephalexin/administration & dosage , Cephalexin/blood , Female , Half-Life , Injections , Meat
10.
Vet J ; 178(2): 238-43, 2008 Nov.
Article in English | MEDLINE | ID: mdl-17768077

ABSTRACT

The pharmacokinetic properties of ceftazidime, a third generation cephalosporin, were investigated in five cats after single intravenous (IV) and intramuscular (IM) administration at a dose rate of 30 mg/kg. Minimum inhibitory concentrations (MICs) of ceftazidime for some Gram-negative (Escherichia coli, n=11) and Gram-positive (Staphylococcus spp., n=10) strains isolated from clinical cases were determined. An efficacy predictor, measured as the time over which the active drug exceeds the bacteria minimum inhibitory concentration (T>MIC), was calculated. Serum ceftazidime disposition was best fitted by a bi-compartmental and a mono-compartmental open model with first-order elimination after IV and IM dosing, respectively. After IV administration, distribution was rapid (t(1/2(d)) 0.04+/-0.03 h), with an area under the ceftazidime serum concentration:time curve (AUC((0-infinity))) of 173.14+/-48.69 microg h/mL and a volume of distribution (V((d(ss)))) of 0.18+/-0.04 L/kg. Furthermore, elimination was rapid with a plasma clearance of 0.19+/-0.08 L/hkg and a t(1/2) of 0.77+/-0.06 h. Peak serum concentration (C(max)), T(max), AUC((0-infinity)) and bioavailability for the IM administration were 89.42+/-12.15 microg/mL, 0.48+/-0.49 h, 192.68+/-65.28 microg h/mL and 82.47+/-14.37%, respectively. Ceftazidime MIC for E. coli ranged from 0.0625 to 32 microg/mL and for Staphylococcus spp. from 1 to 64 microg/mL. T>MIC was in the range 35-52% (IV) and 48-72% (IM) of the recommended dosing interval (8-12h) for bacteria with a MIC(90)4 microg/mL.


Subject(s)
Anti-Bacterial Agents/pharmacokinetics , Cats/metabolism , Ceftazidime/pharmacokinetics , Animals , Anti-Bacterial Agents/administration & dosage , Ceftazidime/administration & dosage , Cross-Over Studies , Female , Injections, Intramuscular/veterinary , Injections, Intravenous/veterinary , Male
11.
J Vet Pharmacol Ther ; 30(4): 345-52, 2007 Aug.
Article in English | MEDLINE | ID: mdl-17610408

ABSTRACT

The pharmacokinetic properties of ceftriaxone, a third-generation cephalosporin, were investigated in five cats after single intravenous, intramuscular and subcutaneous administration at a dosage of 25 mg/kg. Ceftriaxone MICs for some gram-negative and positive strains isolated from clinical cases were determined. Efficacy predictor (t > MIC) was calculated. Serum ceftriaxone disposition was best fitted by a bicompartmental and a monocompartmental open models with first-order elimination after intravenous and intramuscular and subcutaneous dosing, respectively. After intravenous administration, distribution was fast (t1/2d 0.14 +/- 0.02 h) and moderate as reflected by the volume of distribution (V(d(ss))) of 0.57 +/- 0.22 L/kg. Furthermore, elimination was rapid with a plasma clearance of 0.37 +/- 0.13 L/h.kg and a t1/2 of 1.73 +/- 0.23 h. Peak serum concentration (Cmax), tmax and bioavailability for the intramuscular administration were 54.40 +/- 12.92 microg/mL, 0.33 +/- 0.07 h and 85.72 +/- 14.74%, respectively; and for the subcutaneous route the same parameters were 42.35 +/- 17.62 microg/mL, 1.27 +/- 0.95 h and 118.28 +/- 39.17%. Ceftriaxone MIC for gram-negative bacteria ranged from 0.0039 to >8 microg/mL and for gram-positive bacteria from 0.5 to 4 microg/mL. t > MIC was in the range 83.31-91.66% (10-12 h) of the recommended dosing interval (12 h) for Escherichia coli (MIC90 = 0.2 microg/mL).


Subject(s)
Anti-Bacterial Agents/pharmacokinetics , Cats/metabolism , Ceftriaxone/pharmacokinetics , Animals , Anti-Bacterial Agents/administration & dosage , Anti-Bacterial Agents/blood , Area Under Curve , Ceftriaxone/administration & dosage , Ceftriaxone/blood , Female , Gram-Negative Bacteria/drug effects , Gram-Positive Bacteria/drug effects , Injections, Intramuscular/veterinary , Injections, Intravenous/veterinary , Injections, Subcutaneous/veterinary , Male , Microbial Sensitivity Tests
12.
J Vet Pharmacol Ther ; 30(2): 127-31, 2007 Apr.
Article in English | MEDLINE | ID: mdl-17348897

ABSTRACT

The purpose of this study was to investigate whether previous administration of metoclopramide affects cephalexin pharmacokinetics after its oral administration in dogs as well as whether these changes impair its predicted clinical efficacy. Six healthy beagle dogs were included in this study. Oral 25 mg/kg cephalexin monohydrate and intravenous 0.5 mg/kg metoclopramide HCl single doses were administered. Each dog received cephalexin or cephalexin following metoclopramide, with a 2-week washout period. Plasma concentrations of cephalexin were determined by microbiological assay. Cephalexin peak plasma concentration and area under the curve from 0 to infinity significantly increased from 18.77+/-2.8 microg/mL and 82.65+/-10.4 microg.h/mL to 21.88+/-0.8 microg/mL and 113.10+/-20.9 microg.h/mL, respectively, after pretreatment with metoclopramide. No differences between treatments were found for other pharmacokinetic parameters. Pharmacokinetic/pharmacodynamic indices calculated for highly susceptible staphylococci were similar for both experiences. Metoclopramide pretreatment may have increased cephalexin absorption by affecting its delivery to the intestine, and/or enhancing intestinal transporter PEPT1 function. Neither difference in the efficacy of cephalexin nor an increase in toxicity is expected as a result of this modification. Consequently, no dose adjustment is required in cephalexin-treated patients pretreated with metoclopramide.


Subject(s)
Anti-Bacterial Agents/pharmacokinetics , Antiemetics/pharmacology , Cephalexin/pharmacokinetics , Dogs/metabolism , Metoclopramide/pharmacology , Administration, Oral , Animals , Anti-Bacterial Agents/administration & dosage , Anti-Bacterial Agents/blood , Antiemetics/administration & dosage , Antiemetics/blood , Area Under Curve , Cephalexin/administration & dosage , Cephalexin/blood , Infusions, Intravenous/veterinary , Intestinal Absorption , Metoclopramide/administration & dosage , Metoclopramide/blood
13.
J Vet Pharmacol Ther ; 30(1): 80-5, 2007 Feb.
Article in English | MEDLINE | ID: mdl-17217406

ABSTRACT

The objectives of this work were to compare the pharmacokinetics of erythromycin administered by the intramuscular (i.m.) and intravenous (i.v.) routes between nonlactating and lactating goats and to determine the passage of the drug from blood into milk. Six nonpregnant, nonlactating and six lactating goats received erythromycin by the i.m. (15 mg/kg) and the i.v. (10 mg/kg) routes of administration. Milk and blood samples were collected at predetermined times. Erythromycin concentrations were determined by microbiological assay. Results are reported as mean +/- SD. Comparison of the pharmacokinetic profiles between nonlactating and lactating animals after i.v. administration indicated that significant differences were found in the mean body clearance (8.38 +/- 1.45 vs. 3.77 +/- 0.83 mL/kg x h respectively), mean residence time (0.96 +/- 0.20 vs. 3.18 +/- 1.32 h respectively), area under curve from 0 to 12 h (AUC(0-12)) (1.22 +/- 0.22 vs. 2.76 +/- 0.58 microg x h/mL respectively) and elimination half-life (1.41 +/- 1.20 vs. 3.32 +/- 1.34 h); however, only AUC(0-12) showed significant differences after the i.m. administration. Passage of erythromycin in milk was high (peak milk concentration/peak serum concentration, 2.06 +/- 0.36 and AUC(0-12milk)/AUC(0-12serum),6.9 +/- 1.05 and 2.37 +/- 0.61 after i.v. and i.m. administrations respectively). We, therefore, conclude that lactation affects erythromycin pharmacokinetics in goats.


Subject(s)
Erythromycin/pharmacokinetics , Goats/metabolism , Milk/metabolism , Animals , Area Under Curve , Cross-Over Studies , Erythromycin/administration & dosage , Erythromycin/blood , Female , Injections, Intramuscular/veterinary , Injections, Intravenous/veterinary , Lactation
14.
J Vet Pharmacol Ther ; 28(5): 419-23, 2005 Oct.
Article in English | MEDLINE | ID: mdl-16207303

ABSTRACT

The aims of this study were to describe and compare the pharmacokinetic profiles and T(>MIC90) of two commercially available once-daily recommended cephalexin formulations in healthy adult dogs administered by the intramuscular (i.m.) route. Six beagle dogs received a 10 mg/kg dose of an 18% parenteral suspension of cephalexin of laboratory A (formulation A) and laboratory B (formulation B) 3 weeks apart. Blood samples were collected in predetermined times after drug administration. The main pharmacokinetic parameters were (mean +/- SD): AUC((0-infinity)), 72.44 +/- 15.9 and 60.83 +/- 13.2 microg.h/mL; C(max), 10.11 +/- 1.5 and 8.50 +/- 1.9 microg/mL; terminal half-life, 3.56 +/- 1.5 and 2.57 +/- 0.72 h and MRT((0-infinity)), 5.86 +/- 1.5 and 5.36 +/- 1.2 h for formulations A and B, respectively. T(>MIC90) was 63.1 +/- 14.7 and 62.1 +/- 14.7% of the dosing interval for formulations A and B, respectively. Median (range) for t(max) was 2.0 (2.0-3.0) h and 3.0 (2.0-4.0) for formulations A and B, respectively. Geometric mean ratios of natural log-transformed AUC((0-infinity)) and C(max) and their 90% confidence intervals (CI) were 0.84 (0.72-0.98) and 0.83 (0.64-1.07), respectively. The plasma profiles of cephalexin following the administration of both formulations were similar. No statistical differences between pharmacokinetic parameters or T(>MIC90) were observed, however, bioequivalence between both formulations could not be demonstrated, as lower 90% CI failed to fell within the selected range of 80-125% for bioequivalence.


Subject(s)
Anti-Bacterial Agents/pharmacokinetics , Cephalexin/pharmacokinetics , Dogs/metabolism , Animals , Anti-Bacterial Agents/administration & dosage , Anti-Bacterial Agents/blood , Area Under Curve , Cephalexin/administration & dosage , Cephalexin/blood , Chemistry, Pharmaceutical , Drug Administration Schedule , Female , Injections, Intramuscular/veterinary , Male
15.
Vet J ; 170(2): 222-9, 2005 Sep.
Article in English | MEDLINE | ID: mdl-16129342

ABSTRACT

The pharmacokinetic properties of marbofloxacin, a third generation fluoroquinolone, were investigated in six cats after single intravenous (IV) and repeat oral (PO) administration at a daily dose of 2 mg/kg. Marbofloxacin serum concentration was analysed by microbiological assay using Klebsiella pneumoniae ATCC 10031 as micro-organism test. Serum marbofloxacin disposition was best described by bicompartmental and mono-compartmental open models with first-order elimination after IV and oral dosing respectively. After IV administration, distribution was rapid (T(1/2(d)) 0.23+/-0.24 h) and wide, as reflected by the steady-state volume of distribution of 1.01+/-0.15 L/kg. Elimination from the body was slow with a body clearance of 0.09+/-0.02 L/h kg and a T(1/2) of 7.98+/-0.57 h. After repeat oral administration, absorption half-life was 0.86+/-1.59 h and T(max) of 1.94+/-2.11 h. Bioavailability was almost complete (99+/-29%) with a peak plasma concentration at the steady-state of 1.97+/-0.61 mug/mL. Drug accumulation was not significant after six oral administrations. Calculation of efficacy predictors showed that marbofloxacin has good therapeutic profile against Gram-negative and Gram-positive bacteria with a MIC(50) value <0.25 microg/mL.


Subject(s)
Anti-Bacterial Agents/administration & dosage , Anti-Bacterial Agents/pharmacokinetics , Cats , Fluoroquinolones/administration & dosage , Fluoroquinolones/pharmacokinetics , Quinolones/administration & dosage , Quinolones/pharmacokinetics , Administration, Oral , Animals , Anti-Bacterial Agents/blood , Biological Availability , Fluoroquinolones/blood , Injections, Intravenous , Quinolones/blood , Statistics as Topic
16.
J Vet Pharmacol Ther ; 28(4): 363-9, 2005 Aug.
Article in English | MEDLINE | ID: mdl-16050816

ABSTRACT

The pharmacokinetic properties of the fluoroquinolone levofloxacin, were investigated in five cats after single intravenous and repeat oral administration at a daily dose of 10 mg/kg. Levofloxacin serum concentration was analyzed by microbiological assay using Klebsiella pneumoniae ATCC 10031 as test microorganism. Serum levofloxacin disposition after intravenous and oral dosing was best fitted to a bicompartmental and a monocompartmental open models with first-order elimination, respectively. After intravenous administration, distribution was rapid (t(1/2(d)) 0.26 +/- 0.18 h) and wide as reflected by the steady-state volume of distribution of 1.75 +/- 0.42 L/kg. Drug elimination was slow with a total body clearance of 0.14 +/- 0.04 L/h.kg and a t(1/2) for this process of 9.31 +/- 1.63 h. The mean residence time was of 12.99 +/- 2.12 h. After repeat oral administration, absorption half-life was of 0.18 +/- 0.12 h and Tmax of 1.62 +/- 0.84 h. The bioavailability was high (86.27 +/- 43.73%) with a peak plasma concentration at the steady state of 4.70 +/- 0.91 microg/mL. Drug accumulation was not significant after four oral administrations. Estimated efficacy predictors for levofloxacin after either intravenous or oral administration indicate a good profile against bacteria with a MIC value below of 0.5 microg/mL. However, for microorganisms with MIC values of 1 microg/mL it would be efficacious only when administered intravenously.


Subject(s)
Anti-Bacterial Agents/pharmacokinetics , Cats/metabolism , Levofloxacin , Ofloxacin/pharmacokinetics , Administration, Oral , Animals , Anti-Bacterial Agents/administration & dosage , Anti-Bacterial Agents/blood , Anti-Bacterial Agents/pharmacology , Area Under Curve , Drug Administration Schedule , Female , Injections, Intravenous/veterinary , Klebsiella pneumoniae/drug effects , Male , Microbial Sensitivity Tests , Ofloxacin/administration & dosage , Ofloxacin/blood , Ofloxacin/pharmacology
17.
Vet Res Commun ; 28(5): 415-28, 2004 Jul.
Article in English | MEDLINE | ID: mdl-15379436

ABSTRACT

Ketoprofen (KTP) and meloxicam (MLX) are non-steroidal anti-inflamatory drugs used extensively in veterinary medicine. The pharmacokinetics of these drugs were studied in eight dogs following a single oral dose of 1 mg/kg of KTP as a racemate or 0.2 mg/kg of MLX. The concentrations of the drugs in plasma were determined by high-performance liquid chromatography (HPLC). There were differences between the disposition curves of the KTP enantiomers, confirming that the pharmacokinetics of KTP is enantioselective. (S)-(+)-KTP was the predominant enantiomer; the S:R ratio in the plasma increased from 2.58 +/- 0.38 at 15 min to 5.72 +/- 2.35 at 1 h. The area under the concentration time curve (AUC) of (S)-(+)-KTP was approximately 6 times greater than that of (R)-(-)-KTP. The mean (+/- SD) pharmacokinetic parameters for (S)-(+)-KTP were characterized as Tmax = 0.76 +/- 0.19 h, Cmax = 2.02 +/- 0.41 microg/ml, t1/2el = 1.65 +/- 0.48 h, AUC = 6.06 +/- 1.16 microg.h/ml, Vd/F = 0.39 +/- 0.07 L/kg, Cl/F = 170 +/- 39 ml/(kg.h). The mean (+/- SD) pharmacokinetic parameters of MLX were Tmax = 8.5 +/- 1.91 h, Cmax = 0.82 +/- 0.29 microg/ml, t1/2lambda(z) = 12.13 +/- 2.15 h, AUCinf = 15.41 +/- 1.24 microg.h/ml, Vd/F = 0.23 +/- 0.03 L/ kg, and Cl/F = 10 +/- 1.4 ml/(kg.h). Our results indicate significant pharmacokinetic differences between MLX and KTP after therapeutic doses.


Subject(s)
Anti-Inflammatory Agents, Non-Steroidal/pharmacokinetics , Dogs/blood , Ketoprofen/pharmacokinetics , Thiazines/pharmacokinetics , Thiazoles/pharmacokinetics , Animals , Anti-Inflammatory Agents, Non-Steroidal/administration & dosage , Anti-Inflammatory Agents, Non-Steroidal/blood , Area Under Curve , Chromatography, High Pressure Liquid , Female , Half-Life , Ketoprofen/administration & dosage , Ketoprofen/blood , Male , Meloxicam , Metabolic Clearance Rate , Reference Values , Thiazines/administration & dosage , Thiazines/blood , Thiazoles/administration & dosage , Thiazoles/blood
18.
J Vet Pharmacol Ther ; 27(3): 155-62, 2004 Jun.
Article in English | MEDLINE | ID: mdl-15189301

ABSTRACT

The pharmacokinetic properties of ciprofloxacin, a second-generation fluoroquinolone, were investigated in six cats after single intravenous and repeat oral administration at a dosage of 10 mg/kg b.i.d. Ciprofloxacin serum concentration was analyzed by microbiological assay using Klebsiella pneumoniae ATCC 10031 as microorganism test. Serum ciprofloxacin disposition was best fitted to a bicompartmental and a monocompartmental open models with first-order elimination after intravenous and oral dosing respectively. After intravenous administration, distribution was rapid (t(1/2(d)), 0.22 +/- 0.23 h) and wide as reflected by the steady-state volume of distribution of 3.85 +/- 1.34 L/kg. Furthermore, elimination was rapid with a plasma clearance of 0.64 +/- 0.28 L/h.kg and a t(1/2(el)) of 4.53 +/- 0.74 h. After repeat oral administration, absorption was rapid with a half-life of 0.23 +/- 0.22 h and T(max) of 1.30 +/- 0.67 h. However bioavailability was low (33 +/- 12%), the peak plasma concentration at steady-state was 1.26 +/- 0.67 microg/mL. Drug accumulation was not significant after seven oral administrations. When efficacy predictors were estimated ciprofloxacin showed a good profile against gram-negative bacteria when administered either intravenously or orally, although its efficacy against gram-positive microorganisms is lower.


Subject(s)
Anti-Infective Agents/pharmacokinetics , Cats/metabolism , Ciprofloxacin/pharmacokinetics , Klebsiella pneumoniae/drug effects , Administration, Oral , Animals , Anti-Infective Agents/administration & dosage , Anti-Infective Agents/pharmacology , Area Under Curve , Chemistry, Pharmaceutical , Ciprofloxacin/administration & dosage , Ciprofloxacin/pharmacology , Female , Injections, Intravenous/veterinary , Male , Microbial Sensitivity Tests , Veterinary Drugs/administration & dosage , Veterinary Drugs/pharmacokinetics , Veterinary Drugs/pharmacology
19.
J Vet Pharmacol Ther ; 27(1): 21-5, 2004 Feb.
Article in English | MEDLINE | ID: mdl-14995962

ABSTRACT

In this study the pharmacokinetics and renal safety of gentamicin in healthy dogs was investigated after multiple dosing. Six adult male dogs received once-daily gentamicin (6 mg/kg) intramuscularly for 5 days. Serial blood samples were taken on days 1 and 5 of treatment, and at predose, 1 and 6 h on days 2, 3 and 4. Urinalysis, hematology and serum biochemistry evaluation were carried out before, 7 and 14 days after the first gentamicin administration. Mean value of the main pharmacokinetic parameters were: AUC (microg.h/mL), 97.4 and 100.2; terminal half-life (harmonic mean), 0.76 and 1.01 h; ClB/F (mL/min.kg), 1.24 and 1.10; VD(area)/F (L/kg), 0.084 and 0.10; MRT (h), 1.48 and 1.77; Cmax (microg/mL), 54.5 and 49.2; tmax (h), 0.40 and 0.48 for the first and last dose, respectively. Accumulation was determined as R1 = 0.97 and R2 = 1.22. Mean trough gentamicin serum concentrations were 0.06, 0.07, 0.09, 0.1 and 0.1 microg/mL for the first, second, third, fourth and fifth dose, respectively. Statistically significant increases (P < 0.05) were found for last dose MRT and fourth and fifth trough gentamicin serum concentrations. Laboratory tests detected a slight increase in serum creatinine and urea nitrogen concentrations (one dog), decreased specific urine gravity (one dog) and presence of few granular casts (two dogs). It is concluded that once-daily administration of gentamicin may provide adequate serum levels to treat most susceptible gram-negative infections with little or no nephrotoxicity in dogs.


Subject(s)
Anti-Bacterial Agents/pharmacokinetics , Dogs/metabolism , Gentamicins/pharmacokinetics , Animals , Anti-Bacterial Agents/administration & dosage , Anti-Bacterial Agents/blood , Anti-Bacterial Agents/pharmacology , Area Under Curve , Blood Urea Nitrogen , Creatinine/blood , Drug Administration Schedule , Gentamicins/administration & dosage , Gentamicins/blood , Gentamicins/pharmacology , Injections, Intramuscular/veterinary , Male , Specific Gravity , Urinalysis/veterinary
20.
Lab Anim ; 37(3): 188-92, 2003 Jul.
Article in English | MEDLINE | ID: mdl-12869280

ABSTRACT

In order to perform pharmacokinetic studies involving multiple blood sampling, repeated at variable intervals of time, a simple and reliable non-surgical jugular catheterization technique was developed. Six cats were catheterized 48 times using an indwelling through-the-needle type catheter (22G and 20.3 cm) placed into the jugular vein through an over-the-needle type (20G and 32 mm). Catheters remained in place for 1-13 days (median 3 days) without loss of patency until removal. Each jugular was catheterized a range of 2-6 times, with a total indwelling time of 4-33 days. No clinical signs of phlebitis, thrombosis or sepsis were observed either during or after the studies. This technique allows an easy, non-painful, non-stressful blood withdrawal during extended sampling periods, with minimal damage of the veins.


Subject(s)
Blood Specimen Collection/veterinary , Catheterization/veterinary , Cats , Jugular Veins , Animals , Blood Specimen Collection/methods , Catheterization/methods , Female , Male , Pharmacokinetics
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