Pharmacokinetics of Trimethoprim-Sulfamethoxazole in the Green Iguana (Iguana iguana)

A single 30 mg/kg dose of trimethoprim-sulfamethoxazole (TMS) was administered orally (n = 17) and intravenously (n = 13) in a crossover study design, with 10-day washout period, to determine drug pharmacokinetics in healthy adult green iguanas (Iguana iguana). Blood samples were collected at 0 (pre-treatment), 1, 2, 4, 8, 12, 24, 36, 48, 72, and 96h after PO and IV drug administration, including a 6h sample for the IV protocol. Plasma drug concentrations were determined by liquid chromatography-tandem mass spectrometry, and oral bioavailability of trimethoprim (>100%) and sulfamethoxazole (69.4%) were then established. Pharmacokinetic parameters were estimated using a two-stage non-compartmental analysis of naïve-averaged data. Following the crossover study, a multi-dose drug trial was performed to determine steady-state nädir plasma drug concentrations. Green iguanas (n = 10) were given 30 mg/kg TMS PO once daily for seven days, with blood collected from each animal on the eighth day, 24h after the final dose of TMS. Based on once daily oral dosing for seven days, steady-state nädir drug concentrations of trimethoprim and sulfamethoxazole were 396 +/- 116 and 5,290 +/- 5,130 μg/L, which are below the MIC breakpoints of trimethoprim-sulfamethoxazole (≤ 2 μg per mL/38 μg per mL for susceptible organisms and ≥ 4 μg per mL/76 μg per mL for resistant organisms) for human isolates, per the Clinical and Laboratory Standards Institute. However, the ratio of trimethoprim:sulfamethoxazole remained greater than 1:40 up to 12h after single oral dose exposure, and at the 24h sampling after multiple dosing at steady-state.