title: Clarithromycin pharmacokinetics in the desert tortoise (Gopherus agassizii).
abstract: Clarithromycin is a new, safe orally administered macrolide antibiotic active against Mycoplasma sp. in humans. Single-dose and multidose pharmacokinetic parameters were determined for clarithromycin in wild-caught desert tortoises (Gopherus agassizii) seropositive for M. agassizii. Clarithromycin blood levels were measured in three tortoises for up to 72 hr after a single oral dose of 7.5 mg/kg. In a second group of six tortoises, levels were measured after a dose of 15 mg/kg. Noncompartmental iterative two-stage Bayesian and nonparametric expectation maximization pharmacokinetic parameters were determined for each animal assuming first order rate constants. At 15 mg/kg, the maximum concentration was 1.37 microg/ml, the time to maximum concentration was 8.0 hr, and a plasma half-life of 11.69 hr was derived from the latter method. The absorption constant was 0.08/hr, the absorption half-life was 8.47 hr, and the weight-normalized volume of distribution was 5.30 L/kg. Predictions derived by the latter method suggested a dosage of 15 mg/kg p.o. every 24 hr to achieve maximal blood levels of > or =1 microg/ml for multiple dosing. However, results from a preliminary multidose study with three tortoises indicate that the drug is accumulated; therefore, the predicted dose may be closer to 15 mg/kg p.o. every 2-3 days to maintain blood levels of 2-7.5 microg/ml. (For n = 3, 2-point linear regression median estimates for the apparent elimination rate constant (K) and half-life are 0.0227/hr and 30.52 hr, respectively.) This multidose accumulation reflects a slower apparent elimination than that predicted in the eight single-dose tortoises (i.e., K = 0.0593/hr, t1/2 = 11.69 hr). This study highlights a potential pitfall of depending solely on single-dose studies and the potential value of oral administration in reptiles.
authors.affiliation: Department of Clinical Sciences, College of Veterinary Medicine and Biomedical Sciences, Colorado State University, Fort Collins 80523, USA.
authors.forename: J H
authors.initials: JH
authors.lastname: Wimsatt
authors.forename: J
authors.initials: J
authors.lastname: Johnson
authors.forename: B A
authors.initials: BA
authors.lastname: Mangone
authors.forename: A
authors.initials: A
authors.lastname: Tothill
authors.forename: J M
authors.initials: JM
authors.lastname: Childs
authors.forename: C A
authors.initials: CA
authors.lastname: Peloquin
mesh_terms: D000284:Administration, Oral; D000818:Animals; D000900:Anti-Bacterial Agents / Q000008:administration & dosage / Q000493:pharmacokinetics*; D019540:Area Under Curve; D017291:Clarithromycin / Q000008:administration & dosage / Q000493:pharmacokinetics*; D003889:Desert Climate; D006207:Half-Life; D008297:Male; D014426:Turtles / Q000378:metabolism*; D014589:Utah
chemical_list: D000900:Anti-Bacterial Agents; D017291:Clarithromycin