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- Author or Editor: F. Douglas Boudinot x
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Abstract
Objective—To determine pharmacokinetics of troglitazone in healthy cats after IV and oral administration of a single dose of the drug.
Animals—5 healthy ovariohysterectomized adult cats.
Procedure—Using a randomized crossover design, cats were given 5 mg of troglitazone/kg of body weight IV and 40 mg of troglitazone/kg orally. Blood and urine samples were collected after drug administration, and concentrations of troglitazone in plasma and urine were determined by use of high-performance liquid chromatography.
Results—Area-moment analysis was used to calculate pharmacokinetic variables. Terminal phase half-life was 1.1 ± 0.1 hours. Steady-state volume of distribution was 0.23 ± 0.15 L/kg. After IV administration, clearance was 0.33 ± 0.04 L/h/kg. Drug was not detected in urine samples. Mean bioavailability of orally administered troglitazone was 6.9%.
Conclusions and Clinical Relevance—The overall disposition of troglitazone in cats was similar to that reported in other species, including humans. Troglitazone has low and variable oral bioavailability. Clearance of the compound is moderate. Little if any unchanged troglitazone is excreted in urine; thus, metabolism and biliary excretion play predominant roles in elimination of the drug. On the basis of troglitazone pharmacokinetics in healthy cats, as well as on the basis of pharmacodynamics of the drug in humans and other animals, a regimen that uses a dosage of 20 to 40 mg/kg administered orally once or twice per day to cats will produce plasma concentrations of the insulin-sensitizing agent that have been documented to be effective in humans. (Am J Vet Res 2000;61:775–778)
Abstract
Objective—To determine the plasma pharmacokinetics of imipenem (5 mg/kg) after single-dose IV, IM, and SC administrations in dogs and assess the ability of plasma samples to inhibit the growth of Escherichia coli in vitro.
Animals—6 adult dogs.
Procedure—A 3-way crossover design was used. Plasma concentrations of imipenem were measured after IV, IM, and SC administration by use of high-performance liquid chromatography. An agar well antimicrobial assay was performed with 3 E coli isolates that included a reference strain and 2 multidrug-resistant clinical isolates.
Results—Plasma concentrations of imipenem remained above the reported minimum inhibitory concentration for E coli (0.06 to 0.25 µg/mL) for a minimum of 4 hours after IV, IM, and SC injections. Harmonic mean and pseudo-standard deviation halflife of imipenem was 0.80 ± 0.23, 0.92 ± 0.33, and 1.54 ± 1.02 hours after IV, IM, and SC administration, respectively. Maximum plasma concentrations (Cmax) of imipenem after IM and SC administration were 13.2 ± 4.06 and 8.8 ± 1.7 mg/L, respectively. Time elapsed from drug administration until Cmax was 0.50 ± 0.16 hours after IM and 0.83 ± 0.13 hours after SC injection. Growth of all 3 E coli isolates was inhibited in the agar well antimicrobial assay for 2 hours after imipenem administration by all routes.
Conclusions and Clinical Relevance—Imipenem is rapidly and completely absorbed from intramuscular and subcutaneous tissues and effectively inhibits in vitro growth of certain multidrug-resistant clinical isolates of E coli. (Am J Vet Res 2003;64:694–699)
Abstract
Objective—To characterize the pharmacokinetics of zidovudine (AZT) in cats.
Animals—6 sexually intact 9-month-old barrier-reared domestic shorthair cats.
Procedure—Cats were randomly alloted into 3 groups, and zidovudine (25 mg/kg) was administered IV, intragastrically (IG), and PO in a 3-way crossover study design with 2-week washout periods between experiments. Plasma samples were collected for 12 hours after drug administration, and zidovudine concentrations were determined by high-performance liquid chromatography. Maximum plasma concentrations (Cmax), time to reach Cmax (Tmax), and bioavailability were compared between IG and PO routes. Area under the curve (AUC) and terminal phase halflife (t½) among the 3 administration routes were also compared.
Results—Plasma concentrations of zidovudine declined rapidly with t½ of 1.4 ± 0.19 hours, 1.4 ± 0.16 hours, and 1.5 ± 0.28 hours after IV, IG, and PO administration, respectively. Total body clearance and steady-state volume of distribution were 0.41 ± 0.10 L/h/kg and 0.82 ± 0.15 L/kg, respectively. Mean Tmax for IG administration (0.22 hours) was significantly shorter than Tmax for PO administration (0.67 hours). The AUC after IV and PO administration was 64.7 ± 16.6 mg·h/L and 60.5 ± 17.0 mg·h/L, respectively, whereas AUC for the IG route was significantly less at 42.5 ± 9.41 mg·h/L. Zidovudine was well absorbed after IG and PO administration with bioavailability values of 70 ± 24% and 95 ± 23%, respectively.
Conclusions and Clinical Relevance—Cats had slower clearance of zidovudine, compared with other species. Plasma concentrations of zidovudine were maintained above the minimum effective concentration for inhibiting FIV replication by 50% (0.07µM [0.019 µg/mL] for wild-type FIV clinical isolate) for at least 12 hours after IV, IG, or PO administration. (Am J Vet Res 2004;65:835–840)
Abstract
Objective—To characterize the pharmacokinetics of lamivudine (3TC) in cats.
Animals—6 sexually intact 9-month-old barrier-reared domestic shorthair cats.
Procedure—Cats were randomly alloted into 3 groups, and lamivudine (25 mg/kg) was administered IV, intragastrically (IG), and PO in a 3-way crossover study design with 2-week washout periods between experiments. Plasma samples were collected for 12 hours after drug administration, and lamivudine concentrations were determined by high-performance liquid chromatography. Maximum plasma concentrations (Cmax), time to reach Cmax (Tmax), and bioavailability were compared between IG and PO routes. Area under the curve (AUC) and terminal phase halflife (t½) among the 3 administration routes were also compared.
Results—Plasma concentrations of lamivudine declined rapidly with a t½ of 1.9 ± 0.21 hours, 2.6 ± 0.66 hours, and 2.7 ± 1.50 hours after IV, IG, and PO administration, respectively. Total body clearance and steady-state volume of distribution were 0.22 ± 0.09 L/h/kg and 0.60 ± 0.22 L/kg, respectively. Mean Tmax for IG administration (0.5 hours) was significantly shorter than Tmax for PO administration (1.1 hours). The AUC after IV, IG, and PO administration was 130 ± 55.2 mg·h/L, 115 ± 97.5 mg·h/L, and 106 ± 94.9 mg·h/L, respectively. Lamivudine was well absorbed after IG and PO administration with bioavailability values of 88 ± 45% and 80 ± 52%, respectively.
Conclusions and Clinical Relevance—Cats had a shorter t½ but slower total clearance of lamivudine, compared with humans. Plasma concentrations of lamivudine were maintained above the minimum effective concentration for inhibiting FIV replication by 50% (0.14µM [0.032 µg/mL] for wild-type FIV clinical isolate) for at least 12 hours after IV, IG, or PO administration. (Am J Vet Res 2004;65:841–846)
