Pharmacokinetics of oral tramadol in patients with liver cancer.
BACKGROUND
There are no studies reported on pharmacokinetics of opioids in patients with hepatocellular carcinoma, the fifth most common cancer in the world.


METHODS
The authors have studied the pharmacokinetic profile of oral tramadol (50 mg) capsule in 20 patients with liver carcinoma (10 with primary carcinoma on top of chronic hepatitis C and 10 with secondary metastatic liver malignancy as a result of other primary) compared with 10 healthy controls. Plasma tramadol concentrations were measured in venous samples at intervals up to 12 hours by high-pressure liquid chromatography. Allpharmacokinetic variables were evaluated using one-compartment model.


RESULTS
Tramadol bioavailability showed a substantial increase in patients with primary liver cancer and secondary metastatic than that of control (98 percent, 75 percent, and 68 percent, respectively). The area under the serum concentration-time curve increased significantly in patients with primary and metastatic cancer of liver than in control [1,933 microg/h/L (SD = 41), 1,327 microg/h/L (SD = 51), 1,138.5 microg/h/L (SD = 31), respectively]. Also, a significant difference in Cmax and Tmax was found between patients with malignant liver and control. Reduced clearance and impaired elimination was significantly observed in patients with liver carcinoma than control. Clearance was reduced to 50 percent of control, and elimination halflife increased up to three folds in patients with primary liver carcinoma than that of control. Satisfactory pain relief with minimal side effects was observed all over study period.


CONCLUSIONS
It is recommended to lengthen the dose interval of oral tramadol, if it is to be used in patients with liver cancer for analgesic purposes, to 50 mg every 12 hours as it is proved to be effective and safe.
Assiut University Hospital, Anesthesia, Intensive Care, and Pain Management, Assiut, Egypt.
Hassan Ibraheem Mohamed
HI
Kotb
Ihab Ahmed
IA
Fouad
Khaled Mohamed
KM
Fares
Mostafa Galal
MG
Mostafa
Ahmad M
AM
Abd El-Rahman
D000328:Adult; D000368:Aged; D000701:Analgesics, Opioid / Q000493:pharmacokinetics*; D001682:Biological Availability; D006801:Humans; D008113:Liver Neoplasms / Q000503:physiopathology*; D008657:Metabolic Clearance Rate; D008875:Middle Aged; D010148:Intractable Pain / Q000188:drug therapy*; D011446:Prospective Studies; D014147:Tramadol / Q000009:adverse effects / Q000493:pharmacokinetics*
D000701:Analgesics, Opioid; D014147:Tramadol