mobiflex and Kidney-Diseases

Tenoxicam, a new non-steroidal anti-inflammatory drug (NSAID) with an oxicam structure, is entirely ionised at physiological pH, has minimal lipophilic properties, high plasma protein binding, does not accumulate in fatty tissue and skin and thus has a small volume of distribution. Tenoxicam is rapidly and completely absorbed after oral administration. It is entirely metabolised via oxidation and conjugation pathways before elimination. The extraction ratio in the liver is small resulting in a long elimination half-life with a mean of 72 hours. Since no unchanged drug is found in the bile the low half-life cannot be explained by enterohepatic recirculation of parent compound. The low elimination rate of tenoxicam allows for a once-daily dosage (20 mg) regimen. Following multiple dosing during the first two weeks of therapy tenoxicam reaches steady-state levels within 10-20% of predicted values. Several pharmacokinetic factors help make tenoxicam therapy safe and straightforward: it is completely absorbed when taken orally even with meals or antacids, it penetrates easily into synovial fluid, and is excreted as inactive metabolites. Furthermore, drug disposition is not influenced by age, sex or rheumatic disease and unexpected accumulation is not observed.

Topics: Adult; Aged; Aged, 80 and over; Anti-Inflammatory Agents, Non-Steroidal; Drug Administration Schedule; Drug Interactions; Humans; Kidney Diseases; Piroxicam

The 20 mg single-dose and 12 days repeated-dose pharmacokinetics of tenoxicam and the 5-OH-tenoxicam metabolite have been evaluated in healthy volunteers and two groups of patients with different degree of renal impairment, in total 20 persons. Concomitantly, the plasma protein binding of tenoxicam and the effects of treatment on renal function were evaluated. No differences were found between the investigated groups in the pharmacokinetics of total tenoxicam and the 5-OH metabolite did not interfere either with the pharmacokinetics or with the plasma protein binding of tenoxicam. A positive correlation was found between an increase in the free fraction (% F) of tenoxicam in plasma and a decrease in the plasma elimination half-life in the low creatinine clearance group (40-20 ml/min.) both after the single-dose and at steady-state. At steady-state, a non-linear correlation was demonstrated between a decrease in the urinary excretion of the 5-OH metabolite and a decrease in creatinine clearance from 130 to 20 ml/min. An increase in the plasma level of the 5-OH metabolite by three times was found in the low creatinine clearance group as compared to healthy subjects. 14C-Impurities of tenoxicam, as low as 1.2%, were shown to greatly influence the determination of the plasma protein binding (equilibrium dialysis) of the highly protein-bound tenoxicam due to a non-binding ability of the impurities to plasma proteins. No significant changes in renal parameters were found during the study. It can be concluded that the pharmacokinetics and plasma protein binding of tenoxicam and the pharmacokinetics of the 5-OH-tenoxicam metabolite are increasingly changed in subjects with a creatinine clearance below 40 ml/min. A decreased binding of tenoxicam to plasma proteins in low clearance patients is probably the reason for a faster elimination of tenoxicam in this group rather than a higher intrinsic hepatic metabolic activity. This study conducted in a low number of patients did not bring forward any new data indicating any adverse effects of tenoxicam on renal function.

Topics: Adult; Aged; Anti-Inflammatory Agents, Non-Steroidal; Blood Proteins; Creatinine; Dose-Response Relationship, Drug; Female; Humans; Kidney; Kidney Diseases; Kidney Function Tests; Male; Metabolic Clearance Rate; Middle Aged; Piroxicam; Protein Binding; Time Factors

To determine the effectiveness of isosorbide dinitrate in combination with tenoxicam compared with tenoxicam alone for the relief of acute renal colic.. Fifty patients with acute renal colic were randomly and in a double blind fashion divided into two treatment groups of 25 each. Group 1 received tenoxicam (40 mg intravenously) and group 2 received tenoxicam (40 mg intravenously) plus sublingual isosorbide dinitrate (5 mg). The patients were compared for visual pain scores, heart rate and blood pressure between and within the groups before and after treatment.. Comparing the groups, group 2 had significantly lower pain scores after treatment (P < 0.05) but no other variables were significantly different (P > 0.05 for each). Within the groups the pain scores were significantly lower after treatment in both groups (P < 0.05). Group 2 also had a significantly lower heart rate and blood pressure after treatment (P < 0.05). There were no side-effects caused by tenoxicam and isosorbide dinitrate in either group.. The use of tenoxicam alone or combined with isosorbide dinitrate was effective in relieving of renal colic, but the relief obtained with the combination was significantly greater than tenoxicam alone.

Topics: Acute Disease; Adult; Anti-Inflammatory Agents, Non-Steroidal; Blood Pressure; Colic; Double-Blind Method; Drug Therapy, Combination; Female; Heart Rate; Humans; Infusions, Intravenous; Isosorbide Dinitrate; Kidney Diseases; Male; Middle Aged; Pain Measurement; Piroxicam; Treatment Outcome; Vasodilator Agents

Anaesthesia and surgery alter renal function. Inhibition of prostaglandin synthesis by non-steroidal anti-inflammatory drugs (NSAIDs) administered with anaesthesia may further compromise renal function.. To study the effects of tenoxicam (NSAID) administered immediately prior to anaesthesia on renal function in normal individuals undergoing routine surgery.. A randomised single blind placebo controlled study comparing tenoxicam (40 mg intravenously) with placebo was carried out in 20 healthy (ASA I) patients undergoing lower spinal surgery. Glomerular filtration rate (GFR) was determined by creatinine clearance and renal tubular function measured as osmolar and free water clearance.. GFR fell by 60% at the end of surgery but returned to pre-operative values by six hours post-operatively. There was no difference between placebo or tenoxicam with regard to changes in GFR. Tubular function was not altered by tenoxicam.. Current clinical practice of using NSAIDs for post-operative analgesia in low risk individuals appears to have no adverse effects on renal function.

Topics: Adult; Analysis of Variance; Anesthetics, Intravenous; Anti-Inflammatory Agents, Non-Steroidal; Female; Glomerular Filtration Rate; Humans; Intraoperative Complications; Kidney; Kidney Diseases; Laminectomy; Male; Pain, Postoperative; Piroxicam; Postoperative Complications; Premedication; Single-Blind Method; Urodynamics

Forty-seven patients with acute renal colic were treated with either tenoxicam 20 mg i.v. or buscopan compositum (hyoscine butylbromide 20 mg and dipyrone 2.5 g) i.v. in a double blind study. Renal colic was diagnosed with use of a general urine examination, intravenous urogram, ultrasonography or voiding of calculus. The severity of symptoms were assessed by a verbal six point scale. Results demonstrated that 80% of patients treated with tenoxicam and 72.7% of patients treated with buscopan compositum showed significant improvement after 1 hour. Sixty-two percent of the patients who showed initial response to buscopan compositum had pain relapse during next 24 hours and required rescue treatment with pethidine 100 mg i.m. None of the patients treated with tenoxicam i.v. had pain relapse. No side effects were reported with use of tenoxicam. It is concluded that tenoxicam i.v. was more effective than antispasmodics and has rapid onset of analgesia and prolonged action in the treatment of acute renal colic.

Topics: Anti-Inflammatory Agents, Non-Steroidal; Butylscopolammonium Bromide; Colic; Dipyrone; Double-Blind Method; Drug Combinations; Humans; Kidney Diseases; Parasympatholytics; Piroxicam; Prospective Studies; Treatment Outcome

Topics: Adolescent; Adult; Aged; Anti-Inflammatory Agents, Non-Steroidal; Colic; Double-Blind Method; Female; Humans; Injections, Intravenous; Kidney Diseases; Male; Meperidine; Middle Aged; Pain Measurement; Piroxicam; Treatment Outcome

Fifty-eight patients, aged 48-87 years, with impaired renal function and mean initial creatinine clearance of 52.1 mls/min were recruited to a 12-week open study of tenoxicam 20 mg/day for osteoarthrosis or rheumatoid arthritis. Renal function was measured before and after a brief run-in period when patients discontinued all nonsteroidal anti-inflammatory drugs, taking paracetamol alone, prior to monthly monitoring thereafter. Fifty-four % of patients completed the study, the others being withdrawn from lack of efficacy (17%), adverse events (24%) or both (5%). During the run-in period the mean creatinine clearance of 28 patients completing the trial improved to 64.7 mls/min and then dropped to 57.9 mls/min during the course of 12 weeks treatment with tenoxicam. Serial analysis of haematological and biochemical safety parameters showed no drug-induced change of significance. Twenty-three% of patients felt worse and 45% better at the end of treatment. Seventeen patients withdrew because of adverse events. These were normally gastrointestinal and always unrelated to further deterioration in renal function. Tenoxicam, 20 mg/day, can be given safely for a period of at least three months in patients with mild or moderate renal impairment.

Topics: Aged; Aged, 80 and over; Anti-Inflammatory Agents, Non-Steroidal; Arthritis, Rheumatoid; Clinical Trials as Topic; Creatinine; Drug Administration Schedule; Female; Humans; Kidney Diseases; Male; Metabolic Clearance Rate; Middle Aged; Multicenter Studies as Topic; Osteoarthritis; Piroxicam

Topics: Aged, 80 and over; Female; Humans; Kidney Diseases; Piroxicam

To study the possible therapeutic effects on acute renal colic of a single 20 mg intramuscular dose of tenoxicam.. The study comprised 30 patients (22 men and eight women, mean age 32 years, range 17-60) who presented with acute renal colic and were diagnosed by intravenous urography, a general urine examination and ultrasonography. Each patient was treated with 20 mg of tenoxicam given intramuscularly. The severity of pain was assessed on a verbal six-point scale.. Twenty-four patients markedly improved within 1 h of receiving tenoxicam (P < 0.001). No side-effects were reported and the drug was tolerated well by all the patients.. Tenoxicam can be used successfully to treat acute renal colic.

Topics: Acute Disease; Adolescent; Adult; Anti-Inflammatory Agents, Non-Steroidal; Colic; Female; Humans; Injections, Intramuscular; Kidney Diseases; Male; Middle Aged; Piroxicam; Treatment Failure

The pharmacokinetics of tenoxicam after a single oral dose of 20 mg has been studied in 12 patients with various degrees of decreased renal function. Unchanged tenoxicam and its 5'OH-metabolite in plasma and urine were determined by HPLC. The mean areas under the plasma concentration-time curve (138 +/- 53 micrograms/ml X h) and terminal half-lives in patients with impaired renal function did not differ from values previously reported in normal volunteers, nor did the peak concentration of tenoxicam. The half-life of 5'OH-tenoxicam and unchanged tenoxicam where the same. The urinary excretion of 5'OH-tenoxicam fell with decreasing renal function. Thus no dosage adjustment should be necessary and the usual daily dose of tenoxicam may be administered once daily also to patients with renal failure.

Topics: Adult; Aged; Female; Glomerular Filtration Rate; Half-Life; Humans; Kidney Diseases; Kinetics; Male; Middle Aged; Piroxicam; Thiazines