mobiflex and isoxicam

Topics: Animals; Anti-Inflammatory Agents, Non-Steroidal; Dogs; Female; Haplorhini; Humans; Male; Piroxicam; Rats; Thiazines

Investigations have shown that elderly patients have an increased sensitivity to the effects of non-steroidal anti-inflammatory drugs (NSAIDs) with a concomitant higher frequency of side-effects. Several explanations for such an observation are possible including altered receptor responsiveness or changes in absorption and disposition of a drug. From a literature survey it becomes clear that the rate and extent of NSAID absorption do not appear to be changed to a clinically significant degree in the elderly patient. Most NSAIDs are eliminated predominantly by hepatic metabolism and metabolic clearance therefore controls their elimination and accumulation upon chronic dosage. Differences in the dependence of these disposition processes on age exist between the commonly used NSAIDs. In our studies with tenoxicam, steady-state concentrations and accumulation factors did not differ in elderly subjects from those observed in a young population. Therefore, no dosage adjustment of this drug is necessary in elderly patients to achieve similar plasma concentrations following standard dosing in young subjects. Disposition processes of propionic acid derivatives seem to be more affected by advanced age as shown by reports in the literature. Alterations in plasma protein binding, with an increased free fraction of the drug subsequent to changes in serum albumin concentrations were reported with naproxen and salicylates in the aged population. Similarly, ketoprofen and ibuprofen clearance were significantly lower in the elderly than in young volunteers, and an accumulation of naproxen was reported in the elderly after multiple dosing.

Topics: Adult; Age Factors; Aged; Anti-Inflammatory Agents, Non-Steroidal; Biological Transport; Female; Half-Life; Humans; Male; Metabolic Clearance Rate; Middle Aged; Naproxen; Phenylpropionates; Piroxicam

In this work it is explained, by the first time, the application of programs SQUAD and HYPNMR to refine equilibrium constant values through the fit of electrophoretic mobilities determined by capillary zone electrophoresis experiments, due to the mathematical isomorphism of UV-vis absorptivity coefficients, NMR chemical shifts and electrophoretic mobilities as a function of pH. Then, the pK(a) values of tenoxicam in H(2)O/DMSO 1:4 (v/v) have been obtained from (1)H NMR chemical shifts, as well as of oxicams in aqueous solution from electrophoretic mobilities determined by CZE, at 25 degrees C. These values are in very good agreement with those reported by spectrophotometric and potentiometric measurements.

Topics: Algorithms; Electrophoresis, Capillary; Hydrogen-Ion Concentration; Kinetics; Magnetic Resonance Spectroscopy; Meloxicam; Models, Chemical; Molecular Structure; Piroxicam; Software; Stereoisomerism; Thiazines; Thiazoles

Topics: Adult; Adverse Drug Reaction Reporting Systems; Anti-Inflammatory Agents, Non-Steroidal; Drug Eruptions; Female; Humans; Middle Aged; Piroxicam

The binding characteristics of several oxicam derivatives (tenoxicam, 4-hydroxy-2-methyl-N-phenyl-2H-1,2-benzothiazixine-3- carboxamide-1,1-dioxide (CP 14,304), 4-hydroxy-2-methyl-N-2-(3-methyl)-pyridyl-2H-1,2-benzothiazixine-3 -carboxamide- 1,1-dioxide (CP 16,460), piroxicam, meloxicam [corrected], isoxicam, 5-hydroxy-piroxicam) to 2% and 4% human serum albumin (HSA) were determined using a modified ultrafiltration process. The binding properties to HSA were characterized by determining the overall binding constant, the apparent binding constant, the slope, the free reaction energy, and the unbound portion of the drug. The following results were obtained: 1. These oxicam derivatives show a high affinity to HSA. The unbound fraction amounts to 1-3%. 2. The affinity of the compounds to HSA decreases in the order mentioned above. 3. Doubling of the HSA concentration reduces the unbound fraction, to the half, with piroxicam being the only exception.

Topics: Anti-Inflammatory Agents, Non-Steroidal; Chemical Phenomena; Chemistry; Humans; Piroxicam; Serum Albumin; Ultrafiltration

The chronicity of the inflammatory process requires persistent tissue concentrations of non-steroidal anti-inflammatory drugs (NSAIDs), best achieved by using a drug with a long half-life as a once-daily regimen. The oxicams proved to be one of the most promising classes of NSAIDs. They have a similar molecular structure, though substitution of the benzothiazine ring by a thienothiazine system gives tenoxicam a more hydrophilic character. Tenoxicam is thus characterised by lower penetration into tissues requiring more lipophilic properties, e.g. the CNS and skin and, consequently, a lower incidence of adverse reactions at these target organs. Poor diffusion into hepatic cells--as a result of a small free fraction, tight binding to proteins and hydrophilic character--explains its low hepatic extraction ratio and--as a consequence--a long half-life. Compared to indomethacin and diclofenac, the oxicams have a moderate inhibitory activity on the synthesis and release of prostaglandins; tenoxicam is half as active as piroxicam, reflecting the correspondent difference in their steady-state plasma concentrations.

Topics: Anti-Inflammatory Agents, Non-Steroidal; Blood Proteins; Chemical Phenomena; Chemistry; Humans; Piroxicam; Prostaglandin Antagonists; Protein Binding

The chronicity of the inflammatory process requires persistent tissue concentrations of non-steroidal anti-inflammatory drugs (NSAIDs), best achieved by using a drug with a long half-life as a once-daily regimen. The oxicams proved to be one of the most promising classes of NSAIDs. They have a similar molecular structure, though substitution of the benzothiazine ring by a thienothiazine system gives tenoxicam a more hydrophilic character. Tenoxicam is thus characterised by lower penetration into tissues requiring more lipophilic properties, e.g. the CNS and skin, and this may explain the lower incidence of adverse reactions at these target organs in comparison with more lipophilic NSAIDs. Poor diffusion into hepatic cells--as a result of a small free fraction, tight binding to proteins and hydrophilic character--explains its low hepatic extraction ratio and--as a consequence--a long half-life. Compared to indomethacin and diclofenac, the oxicams have a moderate inhibitory activity on the synthesis and release of prostaglandins; tenoxicam is half as active as piroxicam, reflecting the correspondent difference in their steady-state plasma concentrations.

Topics: Anti-Inflammatory Agents, Non-Steroidal; Humans; Piroxicam; Prostaglandins

1 Oxicams have certain distinctive properties, which distinguish them from other arylalkanoic (carboxylic) acids that show anti-inflammatory/analgesic/antipyretic activities. These include: (i) slow rates of metabolism (ii) lesser gastro-irritancy/ulcerogenicity (iii) preventing fever development (iv) some effect on the adaptive responses of the liver to severe inflammation or trauma that compromise normal hormone/xenobiotic metabolism (detoxification). 2 Isoxicam was notably less gastrotoxic than either piroxicam or tenoxicam, when given either orally or parenterally, at equipotent doses in rats.

Topics: Animals; Anti-Inflammatory Agents, Non-Steroidal; Drug Interactions; Female; Liver; Male; Piroxicam; Rats; Stomach Diseases

Determinations of the pKa-values by the spectrophotometric method indicate significant differences in the acidic behaviour between piroxicam and tenoxicam on the one hand and isoxicam on the other. In the case of the first named 2-pyridyl-substituted substances the two measurable and due to the UV-shift individually assignable pKa-values might be explained by the existence of zwitterionic species. In contrast to this isoxicam exhibits only one pKa-value for the enole-enolate system in the pH-range 1-14.

Topics: Chemical Phenomena; Chemistry, Physical; Hydrogen-Ion Concentration; Ions; Piroxicam; Potentiometry; Spectrophotometry, Ultraviolet; Thiazines