Influence of liver cirrhosis upon the pharmacokinetics of tenoxicam.
The effects of impaired hepatic function upon the pharmacokinetics of tenoxicam were studied in six patients with cirrhotic liver disease who ingested a single, oral 20 mg dose of the drug. Data from these patients were compared with those obtained from 14 healthy subjects who received the same regimen. Virtually all of the pharmacokinetic parameters computed for the two groups were similar. Cmax in the cirrhotic patients was 2.63 micrograms/ml (s.d. = 0.92) and tmax was 2.5 h (s.d. = 0.8). The corresponding values for the control subjects were 2.77 micrograms/ml (s.d. = 0.72) and 3.2 h (s.d. = 1.6), respectively. The elimination half-life (t1/2) was 53.0 h (s.d. = 19.0) in the cirrhotic patients and 69.2 h (s.d. = 19.3) in the controls. There were no significant (p greater than 0.05) differences between groups with respect to any of these values. Area under curve was significantly (p less than 0.05) smaller in the cirrhotic patients (159 micrograms.h/ml; s.d. = 65) than in the controls (254 micrograms.h/ml; s.d. = 92). The urinary excretion of the 5'-hydroxy metabolite of tenoxicam averaged 21.6% (s.d. = 3.8) of the administered dose in the cirrhotic patients and 22.1% (s.d. = 3.1) in the control subjects. The plasma protein binding of tenoxicam was also very similar in the two groups. The unbound drug fraction averaged 0.8% (s.d. = 0.3) in the cirrhotic patients and 0.8% (s.d. = 0.1) in the 12 control subjects who contributed data to this portion of the study. The single-dose data presented in this report demonstrated substantially unaltered kinetics with no evidence of impaired elimination and drug retention.(ABSTRACT TRUNCATED AT 250 WORDS)
Crevoisier
C
C
Pharma Clinical Research Department, F. Hoffmann-La Roche & Co., Basle, Switzerland.
Zaugg
P Y
PY
Heizmann
P
P
Meyer
J
J
D000328:Adult; D000894:Anti-Inflammatory Agents, Non-Steroidal / Q000097:blood / Q000493:pharmacokinetics*; D002853:Chromatography, Liquid; D005260:Female; D006801:Humans; D008103:Liver Cirrhosis / Q000378:metabolism*; D008297:Male; D010894:Piroxicam / Q000031:analogs & derivatives* / Q000097:blood / Q000493:pharmacokinetics; D011485:Protein Binding; D013997:Time Factors
D000894:Anti-Inflammatory Agents, Non-Steroidal; D010894:Piroxicam; C032801:tenoxicam