PHARMACOKINETICS OF MELOXICAM IN PATIENTS WITH HEPATIC CIRRHOSIS IN COMPARISON WITH HEALTHY-VOLUNTEERS

The pharmacokinetics of meloxicam were investigated in 12 patients wit h clinically stable liver cirrhosis after a single oral dose of 15mg. 12 healthy volunteers received the same regimen in earlier studies and the results of both groups were compared. Only minor differences in p harmacokinetic parameters were observed between the 2 groups. However, equivalence between the 2 groups could not be demonstrated, probably because of the large variation in the liver function status of the pat ients with cirrhosis. Mean maximum plasma concentration (C-max) in the cirrhotic patients was 0.84 mg/L and the time to C-max(t(max)) was 10 .3 hours. The corresponding values for the healthy volunteers were 0.9 1 mg/L and 7.0 hours, respectively. The elimination half-life (t1/2) w as 16.4 hours in the cirrhotic patients and 21.2 hours in the healthy volunteers. The area under the plasma concentration-time curve (AUG) w as approximately 25% lower in the cirrhotic patients (25.1 mg/L . h) t han in the controls (31.2 mg/L . h). The plasma protein binding of mel oxicam showed no relevant difference between the 2 groups. The cirrhot ic patients revealed an unbound fraction of 0.35%, compared with 0.28% in the healthy controls. Since the data presented in this report show no substantial change in pharmacokinetics, and the drug is not retain ed in hepatically impaired patients, no dosage adjustments appear nece ssary in cirrhotic patients requiring meloxicam treatment.