Raspodjela levofloksacina i njegovo izlučivanje mokraćom u febrilne križane teladi.

Disposition and urinary excretion of levofloxacin following a single intravenous administration of 4 mg/kg body mass were investigated in six febrile crossbred calves. The drug levels in plasma and urine were estimated by microbiological assay. Levofloxacin was rapidly distributed from the blood to the tissue compartment, as evidenced by the high values of the distribution coefficient (9.93 ± 0.73 h -1). The high AUC (11.5 ± 0.95 µg/mL/h) indicated good antibacterial activity of levofloxacin in calves. The elimination half-life, volume of distribution and total body clearance were 2.22 ± 0.07 h, 1.18 ± 0.15 L/kg and 0.36 ± 0.03 L/kg/h, respectively. About 37.7 per cent of the administered dose of levofloxacin was eliminated in urine within 24 h. An appropriate intravenous dosage regimen for levofloxacin would be 5.0 mg/kg, repeated at 12 h intervals for the treatment of bacterial infections, manifested with fever in calves.Istražena je raspodjela levofloksacina i njegovo izlučivanje mokraćom nakon jednokratne intravenske primjene u dozi od 4 mg/kg tjelesne mase u šestero febrilne križane teladi. Razine lijeka u plazmi i mokraći bile su procijenjene na osnovi mikrobiološkog postupka. Levofloksacin se brzo proširio iz krvi u tkiva što je vidljivo po visokim vrijednostima koeficijenta raspodjele (9,93 ± 0,73 h). Visoki AUC (površina ispod krivulje) (11,5 ± 0,95 µg/mL/sat) upućuje na dobro antibakterijsko djelovanje levofloksacina u teladi. Poluvrijeme eliminacije iznosilo je 2,22 ± 0,07 sati, volumen raspodjele 1,18 ± 0,15 L/kg, a ukupni klirens 0,36 ± 0,03 L/kg/sat. Oko 37,7% primijenjene doze levofloksacina bilo je tijekom 24 sata izlučeno putem mokraće. Kod bakterijskih zaraza što se očituju vrućicom levofloksacin treba primijeniti u dozi od 5,0 mg/kg u razmaku od 12 sati

Farmakokinetika i doziranje florfenikola kod istodobne primjene s paracetamolom u križane teladi.

The pharmacokinetics of florfenicol were investigated in cross-bred calves treated with a single intravenous administration (20 mg/kg) following a single intramuscular injection of paracetamol (50 mg/kg). The concentration of florfenicol in the plasma was estimated by microbiological assay technique, using E. coli as the test organism. The drug reached a maximum concentration of 31.5 ± 1.45 μg/mL in the plasma at 1 min, and this rapidly declined to 15.6 ± 0.46 μg/mL at 30 min. It was detected in the plasma above the minimum inhibitory concentration up to 12 h after administration. The disposition pattern of florfenicol followed the two-compartment open model. Florfenicol was fairly distributed from the blood to the tissue compartment as evidenced by the moderate values of the distribution coefficient, (2.23 ± 0.18 per h) and the ratio of K12 /K21 (0.82 ± 0.1). The values of AUC and Vdarea were 54.8 ± 1.51 g/mL.h and 1.5 ± 0.06 L/kg respectively. The elimination half-life, MRT and total body clearance were 2.84 ± 0.07 h, 3.61 ± 0.06 h and 0.37 ± 0.01 L/kg/h, respectively. Florfenicol at a dose of 20 mg/kg body weight IV at 12 h interval is sufficient to maintain T>MIC above 80% for bacteria with MIC values 1.0 μg/mL. The favourable pharmacokinetic profile of florfenicol with rapid distribution, high AUC, large Vdarea and 12 h dosing interval suggest that florfenicol may be an appropriate antibacterial when prescribed with paracetamol in cross-bred calves.Istraživana je farmakokinetika jednokratno intravenski primijenjenog florfenikola (20 mg/kg) u križane teladi nakon jednokratne intramuskularne primjene paracetamola (50 mg/kg). Koncentracija florfenikola u plazmi bila je procijenjena mikrobiološkim testom uporabom bakterije E. coli kao testiranog organizma. Lijek je dosegao maksimalnu koncentraciju od 31,5 ± 1,45 μg/mL u plazmi za jednu minutu da bi se njegova koncentracija vrlo brzo, već za 30 minuta, spustila na 15,6 ± 0,46 μg/mL, a potom se u plazmi nalazio iznad minimalne inhibicijske koncentracije do 12 sati nakon primjene. Dispozicija florfenikola odvijala se po modelu dvostrukog odjeljka. Florfenikol se lako proširio iz krvi u tkiva što je dokazano na osnovi umjerenih vrijednosti koeficijenta raspodjele, (2,23 ± 0,18 na sat) i omjera K12/K21 (0,82 ± 0,1). Vrijednost AUC iznosila je 54,8 ± 1,51 g/mL/h, a Vdpovršine 1,5 ± 0,06 L/kg. Poluživot izlučivanja iznosio je 2,84 ± 0,07 h, MRT 3,61 ± 0,06 h, a sveukupni tjelesni klirens 0,37 ± 0,01 L/kg/h. Intravenska primjena florfenikola u dozi od 20 mg/kg tjelesne mase u razmaku od 12 sati dovoljna je za održavanje T>MIC iznad 80% za bakterije s vrijednostima minimalne inhibicijske koncentracije MIC 1,0 μg/mL. Povoljan farmakokinetički profil florfenikola s brzom raspodjelom, visokim AUC, širokim Vdpovršine i 12 h intervalom doziranja pokazuje da on može imati odgovarajući antibakterijski učinak u križane teladi kada se primjenjuje s paracetamolom

Disposition kinetics and dosage regimen of levofloxacin on concomitant administration with paracetamol in crossbred calves

The disposition kinetics of levofloxacin was investigated in six male crossbred calves following single intravenous administration, at a dose of 4 mg/kg body weight, into the jugular vein subsequent to a single intramuscular injection of paracetamol (50 mg/kg). At 1 min after the injection of levofloxacin, the concentration of levofloxacin in plasma was 17.2 ± 0.36 µg/ml, which rapidly declined to 6.39 ± 0.16 µg/ml at 10 min. The drug level above the MIC90 in plasma, was detected for up to 10 h. Levofloxacin was rapidly distributed from blood to the tissue compartment as evidenced by the high values of the distribution coefficient, α (17.3 ± 1.65 /h) and the ratio of K12/K21 (1.83 ± 0.12). The values of AUC and Vdarea were 12.7 ± 0.12 µg.h/ml and 0.63 ± 0.01 l/kg. The high ratio of the AUC/MIC (126.9 ± 1.18) obtained in this study indicated the excellent antibacterial activity of levofloxacin in calves. The elimination half-life, MRT and total body clearance were 1.38 ± 0.01 h, 1.88 ± 0.01 h and 0.32 ± 0.003 l/kg/h, respectively. Based on the pharmacokinetic parameters, an appropriate intravenous dosage regimen for levofloxacin would be 5 mg/kg repeated at 24 h intervals when prescribed with paracetamol in calves

Kinetika raspodjele cefpiroma i njegovo in vitro vezanje na proteine plazme u goveda.

The disposition of cefpirome after single intramuscular (i.m.) administration (10 mg.kg-1) was investigated in five male cross-bred calves and in vitro plasma protein binding was determined. The concentration of cefpirome in the plasma was estimated by the microbiological assay technique. Binding of cefpirome to plasma proteins was determined at different concentration levels by the equilibrium dialysis technique. The peak plasma level of cefpirome after i.m. administration to cattle was attained at 45 min post-dose and the drug was detected in plasma above MIC of 0.5 μg.mL-1 for up to 10 h. The drug disposition followed a one-compartment open model. The values of t1/2Ka, t1/2β and AUC were 0.21 ± 0.01 h, 2.06 ± 0.02 h and 31.7 ± 0.95 μg.mL-1.h, respectively. Cefpirome was bound to the plasma proteins to the extent of 26.0 ± 2.84 percent at the concentration range of 1-100 μg.mL-1. The binding capacity of cefpirome to plasma proteins and the dissociation rate constant of the protein-drug complex were 3.71 ×10-8 ± 0.31 ×10-8 mole.g-1 and 3.43 ×10-7 ± 0.46 ×10-7 mole, respectively.Istražena je raspodjela cefpiroma i njegovo in vitro vezanje na proteine plazme u petero muške bivolje teladi nakon jednokratne intramuskularne primjene u dozi od 10 mg/kg. Koncentracija cefpiroma u plazmi bila je procijenjena pomoću mikrobioloških testova. Njegovo vezanje na proteine plazme određeno je za različite koncentracije pomoću dijalize. Vršna razina cefpiroma u plazmi nakon intramuskularne primjene postignuta je 45 minuta nakon davanja, a lijek je u plazmi bio dokazan iznad MIC od 0,5 μg/mL do 10 sati nakon davanja. Raspodjela lijeka bila je sukladna modelu otvorenosti jednog odjeljka. Vrijednost t1/2Ka iznosila je 0,21 ± 0,01 h, t1/2β 2,06 ± 0,02 h, a AUC 31,7 ± 0,95 μg/mL/h. Cefpirom se vezao na proteine plazme u visini od 26,0 ± 2,84 % u razmaku koncentracije od 1-100 μg/mL. Sposobnost vezanja cefpiroma na proteine plazme bila je 3,71 ×10-8 ± 0,31 ×10-8 mol/g, a konstanta njegova oslobađanja od kompleksa protein-lijek iznosila je 3,43 ×10 7± 0,46 ×10-7 mola

Farmakokinetika i doziranje levofloksacina u bivolje teladi nakon jednokratne potkožne primjene

The present study was conducted on six male buffalo calves to investigate the pharmacokinetics of levofloxacin following a single subcutaneous administration at the dose rate of 3 mg/kg body weight. Appreciable plasma concentration of levofloxacin (0.28 ± 0.01 μg/mL) was detected 2.5 min after injection and the peak plasma level of 2.94 ± 0.07 μg/mL was observed at 1 h. Drug levels of 0.28 ± 0.01 μg/mL in plasma were detected up to 12 h from administration. Rapid absorption of the drug was also evident by the high value of the absorption rate constant (2.53 ± 0.53 /h). The absolute bioavailability of levofloxacin after subcutaneous administration calculated on the basis of AUC (10.5 ± 0.11 μg/mL/h) and Ke (0.272 ± 0.009 /h) after a single intravenous injection in buffalo calves was 44.3 ± 1.76 per cent. The high value of AUC (8.02 ± 0.2 μg/mL/h) reflected major exposure in the buffalo calves. Extensive distribution of the drug into various body fluids and tissues was reflected by the high value of Vdarea (1.06 ± 0.04 L.kg-1). The elimination half-life and MRT were 4.43 ± 0.1 h and 6.71 ± 0.17 h, respectively. On the basis of the pharmacokinetic parameters, the calculated subcutaneous dosage regimen for levofloxacin in buffalo calves was 4.6 mg/kg at 24 h intervals.Farmakokinetika levofloksacina nakon njegove jednokratne supkutane primjene u dozi od 3 mg/kg tjelesne mase određivana je na šest muške bivolje teladi. Mjerljiva koncentracija levofloksacina u plazmi (0,28 ± 0,01 μg/mL) bila je ustanovljena 2,5 minute nakon primjene, a vršna razina od 2,94 ± 0,07 μg/mL ustanovljena je jedan sat nakon primjene. Razina lijeka od 0,28 ± 0,01 μg/mL bila je u plazmi dokazana do 12 sati nakon primjene. Brza apsorpcija lijeka očitovala se u visokoj vrijednosti stupnja apsorpcije (2,53 ± 0,53/h). Apsolutna biološka raspoloživost levofloksacina nakon supkutane primjene izračunana na osnovi AUC (10,5 ± 0,11 μg/mL/h) i Ke (0,272 ± 0,009 /h) nakon jednokratne intravenske primjene iznosila je 44,3 ± 1,76%. Visoka vrijednost AUC (8,02 ± 0,2 μg/mL/h) bila je posljedica velike količine primijenjenoga lijeka. Široka raspodjela lijeka u različitim tjelesnim tekućinama i tkivima očitovala se velikom vrijednošću Vdarea (1,06 ± 0,04 L/kg). Poluživot izlučivanja lijeka iznosio je 4,43 ± 0,1 h, a MRT 6,71 ± 0,17 h. Na osnovi farmakokinetičkih pokazatelja, izračunana supkutana doza levofloksacina u bivolje teladi iznosila je 4,6 mg/kg u razmacima od 24 sata

Disposition kinetics and urinary excretion of cefpirome after intravenous injection in buffalo calves

We investigated the disposition kinetics and urinary excretion of cefpirome in buffalo calves after a single intravenous administration of 10 mg/kg. Also, an appropriate dosage regimen was calculated. At 1 min after injection, the concentration of cefpirome in the plasma was 57.4 ± 0.72 µg/ml, which declined to 0.22 ± 0.01 µg/ml at 24 h. The cefpirome was rapidly distributed from the blood to the tissue compartment as shown by the high distribution coefficient values (8.67 ± 0.46/h), and by the drug's rate of transfer constant from the central to the peripheral compartment, K12 (4.94 ± 0.31/h). The elimination halflife and the volume of distribution were 2.14 ± 0.02 h and 0.42 ± 0.005 l/kg, respectively. Once the distribution equilibrium was reached between the tissues and plasma, the total body clearance (ClB) and the ratio of the drug present in the peripheral to the central compartment (T/P ratio) were 0.14 ± 0.002 l/kg/h and 1.73 ± 0.06, respectively. Based on the pharmacokinetic parameters we obtained, an appropriate intravenous cefpirome dosage regimen for treating cefpiromesensitive bacteria in buffalo calves would be 8.0 mg/kg repeated at 12 h intervals for 5 days, or until persistence of the bacterial infection occurred

Pharmacokinetics and dosage regimen of florfenicol in co-administration with paracetamol in cross bred calves

The pharmacokinetics of florfenicol were investigated in cross-bred calves treated with a single intravenous administration (20 mg/kg) following a single intramuscular injection of paracetamol (50 mg/kg). The concentration of florfenicol in the plasma was estimated by microbiological assay technique, using E. coli as the test organism. The drug reached a maximum concentration of 31.5 ± 1.45 μg/mL in the plasma at 1 min, and this rapidly declined to 15.6 ± 0.46 μg/mL at 30 min. It was detected in the plasma above the minimum inhibitory concentration up to 12 h after administration. The disposition pattern of florfenicol followed the two two-compartment compartment open model. Florfenicol was fairly distributed from the blood to the tissue compartment as evidenced by the moderate values of the distribution coefficient, � � (2.23 ± 0.18 per h) and the ratio of K /K 12 21 (0.82 ± 0.1). The values of AUC and Vd were 54.8 ± 1.51 ��g/mL.h g/mL.h and 1.5 ± 0.06 L/kg respectively. The area elimination half-life, MRT and total body clearance were 2.84 ± 0.07 h, 3.61 ± 0.06 h and 0.37 ± 0.01 L/kg/h, respectively. Florfenicol at a dose of 20 mg/kg body weight IV at 12 h interval is sufficient to maintain T>MIC above 80 % for bacteria with MIC values ��1.0 1.0 μg/mL. The favourable pharmacokinetic profile of florfenicol with rapid distribution, high AUC, large Vd and 12 h dosing interval suggest that florfenicol may be an area appropriate antibacterial when prescribed with paracetamol in cross-bred calves