Pharmacokinetics and tissue concentrations of firocoxib in sows following oral administration.

The objectives of this study were to describe the pharmacokinetics of firocoxib following oral (PO) dosing and intravenous (IV) injection in sows. Seven healthy sows were administered 0.5 mg firocoxib/kg IV. Following a 23-d washout period, sows were administered firocoxib at 4.0 mg firocoxib/kg PO. Blood samples were collected at predetermined times for 72 hr after IV and 120 hr after PO administration. Plasma firocoxib concentration was measured using UPLC-MS/MS, and pharmacokinetic analysis was performed using noncompartmental procedures. Tissue firocoxib concentrations were determined at 5, 10 (n = 2/time point), and 21 d (n = 3) after PO administration. The geometric mean half-life following IV and PO administration was 16.6 and 22.5 hr, respectively. A mean peak plasma concentration (Cmax) of 0.06 µg/ml was recorded at 7.41 hr (Tmax ) after oral administration. Mean oral bioavailability was determined to be 70.3%. No signs of NSAID toxicity were observed on macroscopic and microscopic investigation. Firocoxib was detected in the skin with subcutaneous fat (0.02 µg/g) of one of three sows at 21 days postadministration. Additional work to establish appropriate meat withhold intervals in sows is required. Firocoxib was readily absorbed following PO administration. Further work is needed to better understand the analgesic effects for sows and piglets nursing sows administered firocoxib.

Conformal high dose external radiation therapy, 80.5 Gy, alone for medically inoperable non-small cell lung cancer: a retrospective analysis.

BACKGROUND: Retrospective analysis of patients with medically inoperable non-small cell lung cancer treated with continuous high-dose external beam radiation therapy at the Medical University of South Carolina. METHODS: We identified 35 patients with non-small cell lung cancer treated 1998-2002. None were candidates for resection for reasons including: pulmonary function (n = 23), previous cancer (n = 9), other co-morbidities (n = 2), and refusal of surgery (n = 1). Median percent predicted forced expiratory volume in 1 second was 41.5%. Median age was 71 years. Five patients had more than one primary tumor: three were concurrently treated, two were sequentially treated. Lesion sizes were <3 cm (n = 24); 3-5 cm (n = 12), and >5 cm (n = 5). Nodal stage was as follows: N0 (n = 33) and N1 (n = 2). Radiation therapy was administered once daily: median dose was 80.5 Gy/35 fx/2.3 Gy/fx. The clinical target volume was tumor plus nodes > or =1.0 cm. V20 data were available for 12 patients, with a mean value of 15.7%. RESULTS: Thirty-four patients completed treatment. Median follow-up was 23.0 months. There were 26 deaths: 19 died from non-small cell lung (73%) and seven died from co-morbid illness (27%). Median survival was 24 months (95% CI, 18.0-31.9 months). Four patients were alive with disease, and five were alive disease-free at 10- and 68-month follow-ups. Of 41 lesions, local failure occurred in 15 lesions (37%) of which 3 local failure patients (9%) failed concomitantly in untreated regional lymph nodes. There were no isolated nodal recurrences. Distant progression: 10 patients (29%) of which 6 distant progression without local failure. Two patients who both had prior lobectomies experienced grade 5 toxicities. CONCLUSION: Continuous high-dose external beam radiation therapy 80.5 Gy administered in 35 fractions was tolerated. Treatment-related death was rare (6%) and isolated to patients with prior lobectomies in an extremely high-risk population. Most mortality was lung cancer-related. The dose of 80.5 Gy in 7 weeks is supported for patients with single lesions and no prior lobectomy. Local failure dominates and higher effective doses should be explored.

Referred otalgia in head and neck cancer: a unifying schema.

Pain referred to the ear is a commonly encountered clinical event, and the differential diagnoses that must be considered for pain in a normal ear are numerous. For physicians involved in the treatment of patients with referred ear pain, especially those involved in the care of patients with head and neck malignancies, a basic understanding of the mechanisms involved to produce this phenomenon is required. Several sources offer figures outlining the neuroanatomic basis of nonotogenic ear pain. On occasion, there has been omission of various components in this referred otalgia pathway, however. The authors propose a unified schema and outline potential areas of "nervous system error" giving rise to pain in a clinically normal ear.