title: Gamithromycin plasma and skin pharmacokinetics in sheep.
abstract: This study assessed the plasma kinetics and skin/plasma concentration ratio of the azalide antibiotic gamithromycin (ZACTRAN(®), Merial) in sheep after a single subcutaneous administration at 6 mg/kg bodyweight. Gamithromycin concentrations in plasma samples collected at various intervals up to 21 days following treatment and metacarpal skin obtained from animals at two, five and ten days after treatment were determined by liquid chromatography-tandem mass spectrometry methods. After administration, gamithromycin was rapidly absorbed, and individual maximum plasma concentrations were observed within 6 hours post-dose. Plasma peak concentration was 573 ± 168 ng/ml. The mean area under the plasma concentration versus time curve extrapolated to infinity was 8.00 ± 1.41 µg · hr/ml, and the mean terminal half-life was 34.5 ± 5.4 hours. Gamithromycin skin concentrations were much higher than the plasma concentrations resulting in skin/plasma concentration ratios of approximately 21, 58, and 138 at two, five and ten days post-dose, respectively, demonstrating extensive distribution to skin tissue.
authors.affiliation: Merial GmbH, Kathrinenhof Research Center, Walchenseestr. 8-12, 83101 Rohrdorf, Germany. Electronic address: michael.kellermann@merial.com.
authors.forename: Michael
authors.initials: M
authors.lastname: Kellermann
authors.affiliation: Merial Limited, PKDM, North Brunswick, NJ 08902, USA.
authors.forename: Rose A
authors.initials: RA
authors.lastname: Huang
authors.affiliation: Merial S.A.S., 29 Avenue Tony Garnier, 69007 Lyon, France.
authors.forename: Andrew B
authors.initials: AB
authors.lastname: Forbes
authors.affiliation: Merial GmbH, Kathrinenhof Research Center, Walchenseestr. 8-12, 83101 Rohrdorf, Germany.
authors.forename: Steffen
authors.initials: S
authors.lastname: Rehbein
mesh_terms: D000818:Animals; D000900:Anti-Bacterial Agents / Q000008:administration & dosage / Q000378:metabolism / Q000493:pharmacokinetics*; D001769:Blood / Q000378:metabolism*; D002853:Chromatography, Liquid; D005260:Female; D006207:Half-Life; D007279:Injections, Subcutaneous; D018942:Macrolides / Q000008:administration & dosage / Q000378:metabolism / Q000493:pharmacokinetics*; D008297:Male; D012756:Sheep / Q000378:metabolism*; D012867:Skin / Q000378:metabolism*; D053719:Tandem Mass Spectrometry; D013997:Time Factors
chemical_list: D000900:Anti-Bacterial Agents; D018942:Macrolides; C552399:gamithromycin
keywords: Gamithromycin; Pharmacokinetics; Sheep; Skin/plasma concentration ratio; Subcutaneous injection