The effects of age and gender on the pharmacokinetics of tenidap sodium in patients with rheumatoid arthritis and osteoarthritis.

Abstract

1. This open‐label study was conducted to evaluate the effects of age and gender on the pharmacokinetics of tenidap sodium in patients with either rheumatoid arthritis (RA) or osteoarthritis (OA). 2. A total of 145 male and female patients, 80 with RA (aged 22‐91 years) and 65 with OA (aged 45‐83 years) each received a single dose of 120 mg tenidap sodium. Pharmacokinetic parameters were estimated from individual tenidap plasma concentration‐time curves determined up to 120 h post‐ dose. Tenidap plasma protein binding was determined in the youngest and oldest age groups for both RA and OA patients. 3. In RA patients, age and gender did not significantly affect the disposition of tenidap or the percentage of unbound tenidap in plasma. Only for tmax were statistically significant effects in the analysis of covariance observed and these were attributed to very high tmax values in two female patients. Likewise, in patients with OA, age and gender did not significantly affect the pharmacokinetics of tenidap, although patients with larger body weights had lower Cmax values. 4. Pharmacokinetic parameters were not significantly different between RA and OA patients, except for t1/2, where two outlier RA patients had low values that caused the mean value to be significantly lower in RA (24 h) than in OA (26 h) patients. Pharmacokinetic parameters for pooled values from RA and OA patients were as follows: t1/2 = 25 h, AUC = 538.4 micrograms ml‐ 1 h, Cmax = 21.9 micrograms ml‐1, tmax = 3.2 h.(ABSTRACT TRUNCATED AT 250 WORDS)

Effects of tenidap on the progression of osteoarthritic lesions in a canine experimental model. Suppression of metalloprotease and interleukin‐1 activity

“…Omeprazole's effect on tenidap pharmacokinetics in dogs was determined in a previous study (21), and those results indicated that it does not alter tenidap plasma concentrations. Moreover, when tenidap was administered orally (3 mg/kg twice daily) in combination with omeprazole (20 mg/day), the therapeutic blood concentrations were similar to those observed in tenidap-treated human OA patients (24).…”

“…Bars show the mean and SEM histologic score (see ref. 24 for description of scoring system) for lesions from the 4-week OA dogs, the 12-week OA dogs, and the tenidap-treated dogs. P values were calculated using the MannWhitney U test.…”

Limitation of activity in an acute model of arthritis: Effect of drug treatment

“…In the hamster, near constant blood levels over the entire day (both feeding and non-feeding periods) are obtained when drug is administered in food (manuscript in preparation). Tenidap plasma levels averaged 6 g/ml, well below the 18-27 g/ ml achieved after giving the 120 mg dose to RA patients [16], but close to the levels of the 40 mg OA dose. Several attempts were made to reach RA therapeutic levels by dosing with tenidap in feed at higher levels.…”

“…However, the steady-state levels in the hamster exceeded the concentrations required to maintain complete suppression of cyclooxygenase. In contrast, blood levels of tenidap in the hamster are 3-5 fold below the 20 to 30 g/ml levels seen in man after a therapeutic dose of 120 mg in RA [16]. At these subclinical drug levels, the effect of tenidap on daily distance was equivalent to piroxicam and indomethacin at clinical levels.…”

Tenidap

“…Thus, it appears that dosage adjustment according to age or gender is not required. [22] 3. Therapeutic Trials • Tenidap has been primarily evaluated in the treatment of patients with rheumatoid arthritis.…”