title: Enoxaparin: pharmacokinetics and treatment schedule for cats.
abstract: Detailed pharmacokinetic data are not available for subcutaneously (SC) administered enoxaparin in cats and this causes difficulties in establishing treatment protocols. The aims of this study were (1) to establish pharmacokinetic data of SC administered enoxaparin and (2) to establish a treatment schedule. Six healthy cats received a single SC injection of 1 mg enoxaparin/kg and blood samples were collected before and 1, 2, 3, 4, 6, 8, 10 and 12 h after the injection. Six further healthy cats received 0.75 mg/kg every 6 h for four consecutive days and blood samples were collected before and 2 h after the first and second injection on day 1, and the first injection on days 2 and 4. Anti-factor Xa (FXa) activity, coagulation tests and thromboelastometry assays were performed. Enoxaparin injection was well tolerated. Following the single SC injection Cmax was 0.83 ± 0.08 anti-Xa IU/mL and in 5/6 cats was detected after 2 h (Tmax = 110 ± 25 min). The total clearance was 23.4 ± 4.8 mL/h/kg and the terminal half-life was 2.27 ± 0.4 h. All cats receiving repeated injections reached the defined target peak range of 0.5-1.0 IU/mL by 2 h after the second injection (0.54 [0.50-0.61]; median, [minimum - maximum]) and there was no considerable accumulation subsequently. With the exception of thromboelastometry (especially non-activated), ratio values of coagulation times increased significantly although only slightly (e.g., the maximal value of median activated partial thromboplastin time ratio was 1.27). Significant, although only moderately close relationships with Spearman rank correlation coefficients between 0.424 and 0.558 were calculated between anti-FXa activities and ratios of different coagulation times. A dosage schedule of 0.75 mg/kg four times a day seems suitable for therapeutic use of enoxaparin in cats as it leads to reproducible peak anti-FXa activities within the target range for the treatment of thrombosis in humans. The low inter-individual variation may indicate that monitoring based on anti-FXa activities is not necessary.
authors.affiliation: Small Animal Clinic, University of Veterinary Medicine Hannover, Bünteweg 9, D-30559 Hannover, Germany. Electronic address: Reinhard.Mischke@tiho-hannover.de.
authors.forename: Reinhard
authors.initials: R
authors.lastname: Mischke
authors.affiliation: Small Animal Clinic, University of Veterinary Medicine Hannover, Bünteweg 9, D-30559 Hannover, Germany.
authors.forename: Jette
authors.initials: J
authors.lastname: Schönig
authors.affiliation: Small Animal Clinic, University of Veterinary Medicine Hannover, Bünteweg 9, D-30559 Hannover, Germany.
authors.forename: Elisabeth
authors.initials: E
authors.lastname: Döderlein
authors.affiliation: Institute for Parasitology, University of Veterinary Medicine Hannover, Bünteweg 17, D-30559 Hannover, Germany.
authors.forename: Sonja
authors.initials: S
authors.lastname: Wolken
authors.affiliation: Institute for Parasitology, University of Veterinary Medicine Hannover, Bünteweg 17, D-30559 Hannover, Germany.
authors.forename: Claudia
authors.initials: C
authors.lastname: Böhm
authors.affiliation: Department of Pharmacology, Toxicology and Pharmacy, University of Veterinary Medicine Hannover, Bünteweg 17, D-30559 Hannover, Germany.
authors.forename: Manfred
authors.initials: M
authors.lastname: Kietzmann
mesh_terms: D000818:Animals; D000925:Anticoagulants / Q000008:administration & dosage / Q000493:pharmacokinetics*; D019540:Area Under Curve; D001780:Blood Coagulation Tests / Q000662:veterinary; D002415:Cats / Q000378:metabolism*; D002985:Clinical Protocols; D017984:Enoxaparin / Q000008:administration & dosage / Q000493:pharmacokinetics*; D005260:Female; D006207:Half-Life; D007279:Injections, Subcutaneous / Q000662:veterinary; D008297:Male
chemical_list: D000925:Anticoagulants; D017984:Enoxaparin
keywords: Anti-FXa activity; Cat; Low molecular weight heparin; Pharmacokinetics; ROTEM; Thromboelastometry; Treatment schedule