Multiple-dose pharmacokinetics of ceftriaxone were investigated following 1 g every 12 h (1GMQ12H) and 2 g every 12 h (2GMQ12H) intravenous dosage regimens. In each dosage regimen, seven successive doses were infused at a constant rate over 30 min to 12 normal subjects. Plasma and urine samples were collected after the first and last dose and assayed for ceftriaxone by HPLC. After the first and last dose, the respective mean values of maximum plasma concentrations were 145 and 168 μg/ml for the 1GMQ12H and 255 and 280 μg/ml for the 2GMQ12H dosage regimen. Pharmacokinetic analyses of the data indicated the following: (i) the elimination half-life (6.6 h) and fraction of dose excreted unchanged in the urine (0.37) remained constant with dose and were not affected by the subchronic administration; (ii) steady-state ceftriaxone concentrations in plasma after the last dose indicated a 20% accumulation for both dosage regimens; (iii) the plasma clearance (Cl_p) and apparent volume of distribution (V_d) increased with dose; and (iv) V_d and Cl_p also increased within a dosage regimen (first dose vs. last dose comparison) by a factor of 14% at the 1GMQ12H and 19% at the 2GMQ12H dosage regimen. Utilizing the first dose data of each dosage regimen and assuming linear pharmacokinetics, respective steady-state plasma concentrations were predicted. The predicted concentrations were higher than the observed concentrations by 10% at the 1GMQ12H and by 15% at the 2GMQ12H dosage regimen. The observed increases in V_d and Cl_p as well as the prediction errors may be explained by the concentration-dependent plasma protein binding of ceftriaxone in man. The clinical significance of the increases observed in V_d and Cl_p is probably negligible since the increase in either V_d or Cl_p was not more than 20% even after a two-fold change in the dose. Therefore, linear pharmacokinetics can be reasonably assumed for ceftriaxone under clinical situations.

Zebra finches (Taeniopygia guttata) are songbirds that often undergo surgical procedures as part of research into learning and memory; these surgeries include those for intracranial injections and cranial implants. At our institution, birds receive subcutaneous lidocaine (a local anesthetic) and intramuscular buprenorphine (an opioid analgesic) preoperatively, with buprenorphine continued every 12 h postoperatively for 2 to 3 d. More recently, the possibility of substituting meloxicam (a COX2-selective NSAID) for buprenorphine, or adding meloxicam to the existing analgesia regimen for a more multimodal approach, has been suggested. The enhanced pain control derived from using lidocaine, buprenorphine, and meloxicam could be of particular benefit in finch surgeries that are particularly invasive or complicated. However, although meloxicam is the most popular NSAID used in birds, 7 the optimal dose and frequency for zebra finches are unknown. Publications that describe the pharmacokinetics of meloxicam in diverse, nonpasserine avian species (doses ranging from 0.5 to 3.0 mg/kg IM, IV, SC, or PO) 1,2,6,8-10,12-15,18 report a wide range of elimination half-lifes (t 1/2 ). For example, vultures dosed once with 2 mg/ kg meloxicam IM had an elimination t 1/2 of 0.42 h, 15 whereas African grey parrots had a t 1/2 of 35.3 h after a dose of 1 mg/kg IM. 12 Such results have caused numerous authors to emphasize the need for species-specific pharmacokinetic analyses before administering meloxicam to any bird. Additional concerns when giving an NSAID include the potential for renal damage, as reflected in uric acid levels and kidney histology, 16,17 and for gastrointestinal effects; with intramuscular administration, another potential sequela is necrosis at the injection site. As is often the case in laboratory animal medicine, giving meloxicam to zebra finches constitutes an extralabel use.We performed a study using healthy, adult zebra finches that entailed the administration of 1 or 2 mg/kg meloxicam intramuscularly to help elucidate an optimal dosing regimen, as well as to reveal any evidence of toxicity. Pharmacokinetic parameters were assessed after a single dose, whereas biochemical analytes, Hct, and histology were evaluated after multiple doses. Our findings are the first to characterize the use of meloxicam in a passerine species. Materials and MethodsAnimals. Male (n = 46) and female (n = 46) wildtype zebra finches older than 90 d were involved in the study; all the birds were in good health clinically and had adequate body condition scores. Finches were maintained in an AAALAC-accredited facility under a 12:12-h light:dark cycle, with temperatures from 73 to 77 °F (22.8 to 25.0 °C) and ambient humidity set at 30% to 70%. The main diet was a fortified millet-canary grass seed-oat mix (Supreme Fortified Daily Diet: Finch, Kaytee Products, Chilton, WI), to which a high-protein supplement (High Potency Mash, Harrison's Bird Foods, HBD International, Brentwood, TN), moistened and mixed with minced hard-boiled eggs, wa...