title: Plasma and urine concentrations of marbofloxacin following single subcutaneous administration to cats.
abstract: The pharmacokinetic properties of marbofoxacin, a third generation fluoroquinolone, were investigated in 12 healthy adult cats after single subcutaneous (SC) administration of 2 mg/kg BW (Part I, n=8 cats) and 4 mg/kg BW (Part II, n=4 cats). In each part of the study blood and urine samples were collected before treatment and thereafter for 5 days. The plasma and urine concentrations of marbofloxacin were determined by HPLC with UV detection. Pharmacokinetic calculations were performed for each treated animal using an open one-compartment-model with first-order elimination after SC dosing. Marbofloxacin in plasma (means): Maximum concentrations (Cmax) of about 1.2 and 3.0 microg/ml were measured 2.3 and 4 hours (tmax) after dosing of 2 and 4 mg/kg BW, respectively. Elimination from the body was low with a total clearance (Cl/F) of approximately 0.1 l/h/kg for both dosages. The half-life (t 1/2) for this process was calculated with 8-10 hours. AUC increased almost proportional when doubling the dose, i.e., 19.77 +/- 6.25 microg * h/ml (2 mg/kg BW) and 51.26 +/- 11.83 microg * h/ml (4 mg/kg BW). Plasma kinetics measured were in accordance with data from literature. Marbofloxacin in urine (means): Maximum drug concentrations were detected 4 and 8 hours after dosing with 70 microg/ml (2 mg/kg BW) and 160 microg/ml (4 mg/kg BW), respectively. Inhibitory effects of the urinary matrix on the antimicrobial activity of the drug were taken into account when performing PK/PD calculations. However, a concentration-dependent bactericidal activity (Cmax/MIC > 8-10) which is claimed for fluoroquinolones was sufficiently met with focus on Escherichia (E.) coli (MIC90 0.5 microg/ml). In the same matrix a threshold value of 1.0 microg/ml was undercut 82 and 116 hours after SC dosing, respectively. Hence, a time-dependent bacteria killing kinetic (T > MIC) which may be of relevance for some Gram-positive germs like Staphylococcus spp. (MIC90 1.0 microg/ml) should be covered, too.
authors.affiliation: Institute for Pharmacology, Toxicology and Pharmacy, University of Veterinary Medicine, Foundation, Hannover, Germany. manfred.kietzmann@tiho-hannover.de
authors.forename: Manfred
authors.initials: M
authors.lastname: Kietzmann
authors.forename: Frank
authors.initials: F
authors.lastname: Niedorf
authors.forename: Sabine
authors.initials: S
authors.lastname: Kramer
authors.forename: Marina
authors.initials: M
authors.lastname: Hoffmann
authors.forename: Marc
authors.initials: M
authors.lastname: Schneider
authors.forename: Marc
authors.initials: M
authors.lastname: Vallé
authors.forename: Rüdiger
authors.initials: R
authors.lastname: Pankow
mesh_terms: D000818:Animals; D000900:Anti-Bacterial Agents / Q000008:administration & dosage / Q000097:blood / Q000493:pharmacokinetics* / Q000652:urine; D019540:Area Under Curve; D002415:Cats / Q000097:blood / Q000378:metabolism* / Q000652:urine; D024841:Fluoroquinolones / Q000008:administration & dosage / Q000097:blood / Q000493:pharmacokinetics* / Q000652:urine; D006207:Half-Life; D007279:Injections, Subcutaneous / Q000662:veterinary; D008297:Male
chemical_list: D000900:Anti-Bacterial Agents; D024841:Fluoroquinolones; C080260:marbofloxacin