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- Author or Editor: Charles W. Brockus x
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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)
Abstract
Objective—To evaluate the effects of various flow rates of oxygen administered via 1 or 2 nasal cannulae on the fraction of inspired oxygen concentration (Fio2) and other arterial blood gas variables in healthy neonatal foals.
Animals—9 healthy neonatal (3- to 4-day-old) foals.
Procedures—In each foal, a nasal cannula was introduced into each naris and passed into the nasopharynx to the level of the medial canthus of each eye; oxygen was administered at 4 flow rates through either 1 or both cannulae (8 treatments/foal). Intratracheal Fio2, intratracheal end-tidal partial pressure of carbon dioxide, and arterial blood gas variables were measured before (baseline) and during unilateral and bilateral nasopharyngeal delivery of 50, 100, 150, and 200 mL of oxygen/kg/min.
Results—No adverse reactions were associated with administration of supplemental oxygen except at the highest flow rate, at which the foals became agitated. At individual flow rates, significant and dose-dependent increases in Fio2, Pao2, and oxygen saturation of hemoglobin (Sao2) were detected, compared with baseline values. Comparison of unilateral and bilateral delivery of oxygen at similar cumulative flow rates revealed no differences in evaluated variables.
Conclusions and Clinical Relevance—Results indicated that administration of supplemental oxygen via nasal cannulae appeared to be a highly effective means of increasing Fio2, Pao2, and Sao2 in neonatal foals. These findings may provide guidance for implementation of oxygen treatment in hypoxemic neonatal foals. (Am J Vet Med 2010;71:1081–1088)
