Pharmacokinetics after single intramuscular administration and in vitro plasma protein binding of cefoperazone in cross bred calves

Autor: Jiwan Kumar Gupta, Rakesh Kumar Chaudhary, Vinod Kumar Dumka
Jazyk: angličtina
Rok vydání: 2008
Předmět:
Zdroj: Veterinarski arhiv
Volume 78
Issue 5
ISSN: 1331-8055
0372-5480
Popis: The present study was conducted to investigate the pharmacokinetics of cefoperazone after single intramuscular (i/m) administration of 20 mg.kg-1 into the lateral neck region and its in vitro plasma protein binding in male cross bred calves. The concentration of cefoperazone in plasma samples was estimated by a standard microbiological assay technique using Escherichia coli (ATCC 10536) as the test organism. Appreciable plasma concentration of cefoperazone (1.14 ± 0.07 μg.mL-1) was detected at 1 min after injection and the peak plasma level of 9.76 ± 0.25 μg.mL-1 was observed at 45 min. The drug level above MIC90 in plasma, was detected up to 5 h of administration. Rapid absorption of the drug was also evident by the short absorption half-life (0.55 ± 0.08 h). The overall systemic bioavailability of cefoperazone after intramuscular administration was 48.1 ± 5.33%. The high value of AUC (15.7 ± 0.64 μg.mL-1.h) reflected a vast area of body covered by drug concentration. Extensive distribution of the drug into various body fluids and tissues was reflected by the high value of the steady state volume of distribution (2.95 ± 0.28 L.kg-1). The elimination halflife and MRT were 2.31 ± 0.05 h and 3.62 ± 0.06 h, respectively. The total body clearance (ClB) was 1.28 ± 0.05 L.kg-1.h-1. Cefoperazone was bound to the plasma proteins of calves to the extent of 24.9 ± 1.11%. There was no statistically significant difference in the pharmacokinetic parameters calculated by compartmental and non-compartmental analysis except the values of AUC, AUMC and ClB. On the basis of the pharmacokinetic parameters, an appropriate i/m dosage regimen for cefoperazone in calves would be 26 mg. kg-1 followed by 22 mg.kg-1 at 6 h intervals.
Istražena je farmakokinetika cefoperazona nakon jednokratne intramuskularne primjene u dozi od 20 mg.kg-1 u vratno mišićje i njegovo in vitro vezanje na proteine plazme u križane muške teladi. Koncentracija cefoperazona u uzorcima plazme bila je određena standardnim mikrobiološkim postupkom rabeći bakteriju Escherichia coli (ATCC 10536). Mjerljiva koncentracija cefoperazona u plazmi (1,14 ± 0,07 μg.mL-1) dokazana je jednu minutu nakon ubrizgavanja, a vršna razina od 9,76 ± 0,25 μg.mL-1 ustanovljena je nakon 45 minuta. Koncentracija iznad MIC90 u plazmi ustanovljena je do 5. sata nakon ubrizgavanja. Brza apsorpcija lijeka bila je također vidljiva po brzom poluvremenu apsorpcije (0,55 ± 0,08 sati). Ukupna sistemna bioraspoloživost cefoperazona nakon intramuskularne primjene iznosila je 48,1 ± 5,33%. Visoka vrijednost područja ispod krivulje (AUC) (15,7 ± 0,64 μg.mL-1.h) bila je odraz velikoga područja tijela pod antibiotikom. Opsežna raspodjela lijeka u različitim tjelesnim tekućinama i tkivima bila je odraz visoke vrijednosti postojanoga volumena raspodjele (2,95 ± 0,28 L.kg-1). Poluvrijeme izlučivanja iznosilo je 2,31 ± 0,05, a srednje vrijeme održavanja 3,62 ± 0,06 sati. Ukupan tjelesni klirens (ClB) bio je 1,28 ± 0,05 L.kg-1.h-1. Cefoperazon se vezao na proteine plazme teladi u rasponu od 24,9 ± 1,11%. Nije ustanovljena statistički značajna razlika u farmakokinetičkim pokazateljima analizom po pojedinim odjeljcima, osim za vrijednosti područja ispod krivulje (AUC), područja ispod krivulje netom nakon primjene (AUMC) i ukupnog tjelesnog klirensa. Na temelju farmakokinetičkih pokazatelja, prikladni režim doziranja cefoperazona primijenjenog i/m u teladi bio bi 26 mg.kg-1, a potom po 22 mg.kg-1 u razmacima od 6 sati.
Databáze: OpenAIRE
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