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Pharmacokinetics of oral tramadol in patients with liver cancer

Hassan Ibraheem Mohamed Kotb, MD, Ihab Ahmed Fouad, PhD, Khaled Mohamed Fares, MD, Mostafa Galal Mostafa, MD, Ahmad M. Abd El-Rahman, MSc

Abstract


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. All pharmacokinetic 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 μg/h/L (SD = 41), 1,327 μg/h/L (SD = 51), 1,138.5 μg/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.
Conclusion: 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.

Keywords


analgesics, opioid, tramadol, liver, carcinoma, pharmacokinetics

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DOI: https://doi.org/10.5055/jom.2008.0014

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