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OBJECTIVE To determine tear film concentrations of doxycycline in ophthalmologically normal dogs following oral doxycycline administration.
DESIGN Crossover study.
ANIMALS 10 privately owned dolichocephalic or mesaticephalic dogs free of ophthalmic disease.
PROCEDURES Dogs were randomly assigned to receive doxycycline hyclate first at 5 mg/kg (2.3 mg/lb) or 10 mg/kg (4.5 mg/lb), PO, every 12 hours for 5 days, beginning on day 1. Doxycycline was administered 1 hour prior to feeding. Tear samples were collected from days 1 through 10 approximately 3 hours after the morning dose was administered. Following a 3-week washout period, dogs received the alternative dose in the same conditions. Doxycycline concentration in tear samples from 1 eye (same eye used for both sessions) was measured via liquid chromatography–mass spectrometry and compared between the 2 doxycycline doses.
RESULTS Doxycycline was detected in tear samples of all dogs from days 1 through 10 for both doxycycline doses. Median peak doxycycline concentrations for the 5 mg/kg and 10 mg/kg doses were 2.19 ng/mL on day 3 and 4.32 ng/mL on day 4, respectively. Concentrations differed significantly with time, but this difference was not influenced by dose, dose order, or eye. A significant positive correlation was identified between doxycycline concentration and body weight (r = 0.22).
CONCLUSIONS AND CLINICAL RELEVANCE Detectable doxycycline concentrations were achieved in the tear film of ophthalmologically normal dogs following oral administration of doxycycline at 5 or 10 mg/kg, every 12 hours. Dose had no significant effect on tear film concentration of the drug.
Objective—To compare daily endogenous cortisol production rate and the pharmacokinetics of an IV bolus of hydrocortisone between neonatal foals and adult horses.
Animals—10 healthy full-term 2- to 4-day-old foals and 7 healthy adult horses.
Procedures—Blood samples were collected from each horse every 15 to 20 minutes for 24 hours for determination of 24-hour mean cortisol concentration. Afterward, dexamethasone (0.08 mg/kg) was administered IV to suppress endogenous cortisol production. Twelve hours afterward, hydrocortisone sodium succinate (1.0 mg/kg) was administered as a rapid IV bolus and serial blood samples were collected to determine hydrocortisone pharmacokinetics. Cortisol concentrations, daily cortisol production rate, and hydrocortisone pharmacokinetics were determined, and results were compared between adult horses and foals.
Results—The mean ± SD 24-hour cortisol concentration was significantly lower in foals (20 ± 4 ng/mL) than in horses (26 ± 6 ng/mL), but the daily cortisol production rate was significantly greater in foals (6,710 ± 320 ng/kg/d) than in horses (2,140 ± 400 ng/kg/d). For hydrocortisone, foals had a significantly greater volume of distribution at steady state (1.92 ± 1.11 L/kg) and total body clearance (1.39 ± 0.108 L/kg/h) and significantly lower peak plasma concentration (1,051 ± 343 ng/mL) than did horses (0.58 ± 0.15 L/kg, 0.349 ± 0.065 L/kg/h, and 8,934 ± 3,843 ng/mL, respectively).
Conclusions and Clinical Relevance—Important differences were detected in cortisol production and metabolism between neonatal foals and adult horses consistent with lower plasma protein binding of cortisol in foals. This decrease may contribute to cortisol insufficiency during prolonged critical illness in neonatal foals.
OBJECTIVE To characterize the elution of platinum from carboplatin-impregnated calcium sulfate hemihydrate (CSH) beads in vitro.
SAMPLE 60 carboplatin-impregnated CSH beads and 9 CSH beads without added carboplatin (controls).
PROCEDURES Carboplatin-impregnated CSH beads (each containing 4.6 mg of carboplatin [2.4 mg of platinum]) were placed into separate 10-mL plastic tubes containing 5 mL of PBSS in groups of 1, 3, 6, or 10; 3 control beads were placed into a single tube of PBSS at the same volume. Experiments were conducted in triplicate at 37°C and a pH of 7.4 with constant agitation. Eluent samples were collected at 1, 2, 3, 6, 12, 24, and 72 hours. Samples were analyzed for platinum content by inductively coupled plasma–mass spectrometry.
RESULTS The mean concentration of platinum released per carboplatin-impregnated bead over 72 hours was 445.3 mg/L. Cumulative concentrations of platinum eluted increased as the number of beads per tube increased. There was a significant difference in platinum concentrations over time, with values increasing over the first 12 hours and then declining for all tubes. There was also a significant difference in percentage of total incorporated platinum released into tubes with different numbers of beads: the percentage of eluted platinum was higher in tubes containing 1 or 3 beads than in those containing 6 or 10 beads.
CONCLUSIONS AND CLINICAL RELEVANCE Carboplatin-impregnated CSH beads eluted platinum over 72 hours. Further studies are needed to determine whether implantation of carboplatin-impregnated CSH beads results in detectable levels of platinum systemically and whether the platinum concentrations eluted locally are toxic to tumor cells.
OBJECTIVE To characterize long-term elution of platinum from carboplatin-impregnated calcium sulfate hemihydrate (CI-CSH) beads in vitro by comparing 2 distinct sample collection methods designed to mimic 2 in vivo environments.
SAMPLES 162 CI-CSH beads containing 4.6 mg of carboplatin (2.4 mg of platinum/bead).
PROCEDURES For method 1, which mimicked an in vivo environment with rapid and complete fluid exchange, each of 3 plastic 10-mL conical tubes contained 3 CI-CSH beads and 5 mL of PBS solution. Eluent samples were obtained by evacuation of all fluid at 1, 2, 3, 6, 9, and 12 hours and 1, 2, 3, 6, 9, 12, 15, 18, 22, 26, and 30 days. Five milliliters of fresh PBS solution was then added to each tube. For method 2, which mimicked an in vivo environment with no fluid exchange, each of 51 tubes (ie, 3 tubes/17 sample collection times) contained 3 CI-CSH beads and 5 mL of PBS solution. Eluent samples were obtained from the assigned tubes for each time point. All samples were analyzed for platinum content by inductively coupled plasma–mass spectrometry.
RESULTS Platinum was released from CI-CSH beads for 22 to 30 days. Significant differences were found in platinum concentration and percentage of platinum eluted from CI-CSH beads over time for each method. Platinum concentrations and elution percentages in method 2 samples were significantly higher than those of method 1 samples, except for the first hour measurements.
CONCLUSIONS AND CLINICAL RELEVANCE Sample collection methods 1 and 2 may provide estimates of the minimum and maximum platinum release, respectively, from CI-CSH beads in vivo.