Azithromycin pharmacokinetics in the serum and its distribution to the skin in healthy dogs and dogs with pyoderma.
Serum and skin tissue azithromycin (AZM) concentrations were analysed in healthy and pyoderma affected dogs to determine AZM pharmacokinetics and to establish the effect of disease on AZM skin disposition. AZM was administered orally to two groups of healthy dogs: (1) at 7.02 mg/kg (n=7) and (2) at 11.2mg/kg (n=9). A crossover design was used on five of them. Seven dogs with pyoderma were treated with AZM at 10.7 mg/kg. The two groups of healthy dogs received AZM once daily over three consecutive days and dogs with pyoderma received the same treatment repeated twice with an interval of 1 week. AZM concentrations were determined by liquid chromatography-tandem mass spectrometry. AZM was rapidly absorbed and slowly excreted. In healthy dogs, maximum serum concentrations appeared 2h after administration and were (mean ± standard deviation) 0.60 ± 0.25 μg/mL and 1.03 ± 0.43 μg/mL, and the half-lives were 49.9 ± 5.10 and 51.9 ± 6.69 h for doses of 7.02 and 11.2mg/kg, respectively. Clearance (CL0-24/F) was similar in both dosing groups (1.24 ± 0.24 and 1.29 ± 0.24 L/h/kg) and the respective mean residence time (MRT0-24) was 11.1 ± 0.8 and 8.4 ± 2.2h. The skin concentration in healthy dogs was 3.5-6.5 and 5.0-12.0 times higher than the corresponding serum concentration after the two doses and increased after the cessation of AZM administration. The ratio increased significantly in inflamed tissue (9.5-26.2).
Veterinary Teaching Hospital, The Koret School of Veterinary Medicine, The Hebrew University of Jerusalem, PO Box 12, Rehovot 76100, Israel.
Gila
G
Zur
National Residue Control Laboratory, Kimron Veterinary Institute, Veterinary Services, Ministry of Agriculture, 50250 Beit Dagan, Israel.
Stefan
S
Soback
Veterinary Teaching Hospital, The Koret School of Veterinary Medicine, The Hebrew University of Jerusalem, PO Box 12, Rehovot 76100, Israel.
Yfat
Y
Weiss
Veterinary Teaching Hospital, The Koret School of Veterinary Medicine, The Hebrew University of Jerusalem, PO Box 12, Rehovot 76100, Israel.
Elad
E
Perry
Veterinary Teaching Hospital, The Koret School of Veterinary Medicine, The Hebrew University of Jerusalem, PO Box 12, Rehovot 76100, Israel.
Eran
E
Lavy
National Residue Control Laboratory, Kimron Veterinary Institute, Veterinary Services, Ministry of Agriculture, 50250 Beit Dagan, Israel. Electronic address: malkab@moag.gov.il.
Malka
M
Britzi
D000818:Animals; D000900:Anti-Bacterial Agents / Q000097:blood / Q000493:pharmacokinetics*; D017963:Azithromycin / Q000097:blood / Q000493:pharmacokinetics*; D002853:Chromatography, Liquid / Q000662:veterinary; D018592:Cross-Over Studies; D004283:Dog Diseases / Q000378:metabolism*; D004285:Dogs; D005260:Female; D006207:Half-Life; D008297:Male; D011711:Pyoderma / Q000378:metabolism*; D053719:Tandem Mass Spectrometry / Q000662:veterinary
D000900:Anti-Bacterial Agents; D017963:Azithromycin
Azithromycin; Canine; Pharmacokinetics; Pyoderma; Serum; Skin