DESIGN: Prospective assessment of MDR- and XDR-TB patients starti

DESIGN: Prospective assessment of MDR- and XDR-TB patients starting second-line anti-tuberculosis drug treatment between 1 August 2001 and 31 July 2003, Selleckchem PD-L1 inhibitor with follow-up until 31 December 2010.

RESULTS: In 211 MDR- and XDR-TB patients, treatment success was 61.1%; 22.3% defaulted, 8.5% failed and 8.1% died. TB recurrence among successfully treated patients was 8.5%, with no significant difference between XDR-TB and MDR-TB. TB recurrence was associated with resistance to all injectables (HR 2.27, 95%CI 1.16-5.06, P = 0.046), resistance

to a greater number of drugs (HR 1.35, 95%CI 1.11-1.64, P = 0.003), and sputum smear positivity (HR 2.16, 95%CI 1.16-4.00, P = 0.016). A history of previous TB treatment was associated with TB recurrence among successfully treated patients (HR 4.28, 95%CI 1.13-16.15, P = 0.032).

CONCLUSIONS: The internationally recommended Category IV treatment regimens are sufficiently effective to cure 75% of adherent MDR- and XDR-TB patients. A history of previous treatment, resistance to all injectable agents and resistance to a greater number of drugs increase the recurrence

of MDR- and XDR-TB.”
“In vitro whole blood canine assays were used to quantify the inhibitory actions of the novel non-steroidal anti-inflammatory drug (NSAID) robenacoxib on the cyclooxygenase (COX) isoenzymes, COX-1 and COX-2, in comparison with other drugs of the NSAID class. COX-1 activity was determined by measuring serum thromboxane (Tx)B(2)

synthesis in blood samples allowed to clot at 37 degrees C for 1 h. COX-2 activity U0126 cell line was determined by measuring prostaglandin (PG)E(2) synthesis in blood samples incubated at 37 degrees C for 24 h in the presence of lipopolysaccharide. click here The rank order of selectivity for inhibition of COX-2 versus COX-1 (IC(50) COX-1:IC(50) COX-2) for veterinary drugs was highest with robenacoxib (128.8) compared to deracoxib (48.5), nimesulide (29.2), S+ carprofen (17.6), meloxicam (7.3), etodolac (6.6), R- carprofen (5.8) and ketoprofen (0.88). Selectivity expressed as the clinically relevant ratio IC(20) COX-1:IC(80) COX-2 was highest for robenacoxib (19.8) compared to deracoxib (2.3), S+ carprofen (2.5), R- carprofen (2.1), nimesulide (1.8), etodolac (0.76), meloxicam (0.46) and ketoprofen (0.21).

An in vivo pharmacokinetic ex vivo pharmacodynamic study in the dog established dosage and concentration-effect relationships for single oral doses of robenacoxib over the dosage range 0.5-8.0 mg/kg. Values of C(max) and AUC were linearly related to dosage over the tested range. Robenacoxib did not inhibit serum TxB(2) synthesis (COX-1) ex vivo at dosages of 0.5-4.0 mg/kg and produced only transient inhibition (at the 1 h and 2 h sampling times) at the 8 mg/kg dosage.

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