Pharmacokinetics, urinary excretion and milk penetration of levofloxacin in lactating goats.

摘要: Levofloxacin, a recently introduced third-generation fluoroquinolone, is the L-isomer ofloxacin and possesses excellent activity against Gram-positive, Gram-negative anaerobic bacteria (North et al., 1998). Compared with other fluoroquinolones (FQs), it also has more pronounced bactericidal organisms such as Pseudomonas, Enterobacteriaceae Klebsiella spp. (Klesel 1995). Several species of staphylococci, streptococci including Streptococcus pneumoniae, bacteroides, clostridium, haemophilus, moraxella, legionella, mycoplasma chlamydia are susceptible to levofloxacin (Langtry & Lamb, The effect achieved through reversible binding DNA gyrase subsequent inhibition bacterial replication transcription (Fu 1992). Levofloxacin distributes well target body tissues fluids in respiratory tract, skin, urine prostrate, its uptake by cells makes suitable for use intracellular pathogens. However, penetrates poorly into central nervous system FQs act concentration-dependent killing mechanism, whereby optimal attained administration high doses over short period time (Drusano 1993). This profile associated relatively prolonged postantibiotic (Aliabadi Lees, 2001). drug undergoes limited metabolism rats human 1998) primarily excreted kidney mainly active drug. Inactive metabolites (N-oxide demethyl metabolites) represent <5% total dose (Hurst 2002). pharmacokinetics been fully investigated humans (Chulavatnatol 1999), rabbits (Destache 2001), cats (Albarellos 2005) calves (Dumka Srivastava, 2006, 2007). there no information available on goats. In view marked variation kinetic data antimicrobial drugs, present study was undertaken determine pharmacokinetics, urinary excretion milk penetration following single intravenous (i.v.) intramuscular (i.m.) lactating Tavanic [100 mL vial solution hemihydrate equivalent 500 mg (5 ⁄mL) levofloxacin] purchased from Aventis, Frankfurt, Germany Mueller– Hinton agar Mast Group Ltd., Merseyside, UK. Six adult goats weighing 27–35 kg aged 3 5 years were determined be clinically healthy before based physical examination. fed barley, alfalfa hay wheat straw free access food water. animals did not receive any treatment study. approved Bioethics Committee Faculty Veterinary Medicine, Cairo University. performed two phases, crossover design (2 · 2) 15-day washout between phases. Three given i.v. injection left jugular vein at 4 ⁄kg bodyweight (b.w.) levofloxacin, three injected i.m. semimembranous muscle same dose. Five millilitre venous whole blood samples taken venepuncture 10 heparinized Vacutainers (Becton Dickinson Vacutainer Systems, Rutherford, NJ, USA). sampling times 0 (blank sample), 0.08, 0.166, 0.33, 0.5, 0.75, 1, 2, 4, 6, 8, 10, 12, 18, 24, 36, 48 72 h after treatment. All centrifuged 3000 g 15 min separate plasma. plasma frozen )20 C until analysis. After 2 weeks, that had vice versa. Blood collected processed above. Urine simultaneously various predetermined intervals postadministration. via rubber balloon catheter (Folatex No.12; Sewoon Medical Co., Ltd, Seoul, Korea) previously inserted bladder their volumes measured. Milk hand stripping both halves udder. Complete evacuation udder carried out each sampling. concentration plasma, estimated standard microbiological assay (Bennett 1966) using Escherichia coli ATCC 10536 test micro-organism. method level having antibacterial activity, without differentiating parent metabolites. reasons why we selected bioassay are: (i) measures which could practical pharmacodynamic evaluations than HPLC (McKellar 1999); (ii) precise, reproducible does require neither J. vet. Pharmacol. Therap. 32, 101–104, doi: 10.1111/j.1365-2885.2008.01001.x. SHORT COMMUNICATION