isoxicam and Kidney-Diseases

The effects of a 7 day-treatment with isoxicam (200 mg/24 h) on the urinary excretion of prostaglandins (PG) were compared to those of indomethacin (150 mg/24 h) in a double-blind randomized study conducted in 18 patients with degenerative arthritic disease and normal renal function. Indomethacin decreased the urinary excretion of PGF2 alpha by about 70% and 6-keto-PGF1 alpha and thromboxane (Tx)B2, the stable break-down products of prostacyclin and TxA2 respectively, by about 40%. Isoxicam effects on urinary PG did not significantly differ from those of indomethacin. During both treatments, urinary gamma-glutamyl transferase and N- acetyl-glucosaminidase remained stable and none of the changes in the urinary excretion of PGs could be related to either plasma or urinary drug concentrations. In conclusion, chronic administration of isoxicam inhibited the renal PG biosynthesis to a similar extent than indomethacin which suggests that non steroidal anti-inflammatory drugs of the oxicam group ought also be used cautiously in patients with renal impairment.

Topics: 6-Ketoprostaglandin F1 alpha; Anti-Inflammatory Agents, Non-Steroidal; Arthritis; Dinoprost; Double-Blind Method; Female; Humans; Indomethacin; Kidney Diseases; Male; Middle Aged; Piroxicam; Prostaglandins; Thromboxane B2

The study aimed to predict effective human jejunal permeability (P(eff)) using a biophysical model based on parametrized paracellular, aqueous boundary layer, and transcellular permeabilities, and the villus-fold surface area expansion factor (k(VF)). Published human jejunal data (119 P(eff), 53 compounds) were analyzed by a regression procedure incorporating a dual-pore size paracellular model. Transcellular permeability, scaled by k(VF), was equated to that of Caco-2 at pH 6.5. The biophysical model predicted human jejunal permeability data within the experimental uncertainty. This investigation revealed several surprising predictions: (i) many molecules permeate predominantly (but not exclusively) by the paracellular route, (ii) the aqueous boundary layer thickness in the intestinal perfusion experiments is larger than expected, (iii) the mucosal surface area in awake humans is apparently nearly entirely accessible to drug absorption, and (iv) the relative "leakiness" of the human jejunum is not so different from that observed in a number of published Caco-2 studies.

Topics: Animals; Disease Models, Animal; Dogs; Humans; Jejunal Diseases; Kidney Diseases; Models, Biological; Permeability; Porosity; Regression Analysis

The pharmacokinetics of isoxicam, a new non-steroidal anti-inflammatory drug, were studied in 20 osteoarthritis patients with varying degrees of renal insufficiency. A wide variation in pharmacokinetic parameters was seen between individuals but there was no suggestion that renal function influenced pharmacokinetics. Steady state plasma isoxicam concentrations varied from 20 micrograms/ml to 130 micrograms/ml, while the plasma half-life varied from 23 hours to 58 hours. Despite a reduction in urinary prostaglandin E2 excretion, isoxicam administration did not alter renal function over a 4-week period.

Topics: Aged; Anti-Inflammatory Agents, Non-Steroidal; Female; Humans; Kidney; Kidney Diseases; Kinetics; Male; Middle Aged; Piroxicam