Abstract
The pharmacokinetics of tenoxicam (Ro 12-0068), a thienothiazine derivative with analgesic and anti-inflammatory properties, was studied with 5 healthy male volunteers, 5 elderly male patients, and 4 bedridden elderly female patients. After a single oral administration of 10 mg tenoxicam, the concentrations of tenoxicam in the venous blood and a metabolite of tenoxicam (5'-hydroxy-tenoxicam) in urine were determined at various times by HPLC.
The pharmacokinetic parameters of tenoxicam were calculated by a one-compartment model. The respective Cmax, Tmax, Cl, T1/2, AUC, and Kel between the healthy volunteers and elderly patients were similar in level. The apparent Vd in the healthy volunteers and elderly male and female patients were 0.147, 0.192, and 0.273l/kg, respectively, and the apparent Vd in elderly patients was significantly larger than that in healthy volunteers (P<0.005).
Tenoxicam was not detected in urine and cumulative urinary excretion rate of 5'-hydroxy-tenoxicam in elderly patients was lower than that of the healthy volunteers. The respective serum albumin levels in the healthy volunteers and elderly male and female patients were 4.56, 3.68, and 3.60 g/dl. The correlation between serum albumin levels and age was obtained to be y=-0.017x+4.9 (r=0.805, P<0.001) and the correlation between serum albumin levels and apparent Vd was y=-6.437x+5.235 (r=-0.669, P<0.01). The bioavailability of tenoxicam was about 100% and the protein binding of tenoxicam was 98.5% . From these results, it may be concluded that the increased apparent Vd of tenoxicam in elderly patients was caused by decreased albumin levels in these patients.
