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BJA Advance Access published online on October 29, 2004
British Journal of Anaesthesia, doi:10.1093/bja/aei007
© 2004 by The Board of Management and Trustees of the British Journal of Anaesthesia
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Accepted July 30, 2004

Clinical Investigation

Pharmacokinetics of controlled release morphine (MST) in patients with liver carcinoma

H. I. M. Kotb 1*, S. A. El-Kady 1, S. E. S. Emara 2, E. A. Fouad 3, and M. Y. El-Kabsh 4

1 Department of Anesthesia, Assiut University, Assiut, Egypt
2 Department of Pharmaceutical Analytical Chemistry, Assiut University, Assiut, Egypt
3 Department of Pharmaceutics, Assiut University, Assiut, Egypt
4 Clinical Pathology, Faculty of Medicine, Assiut University, Assiut, Egypt

* To whom correspondence should be addressed.
H. I. M. Kotb, E-mail: kotbhi{at}yahoo.com


  Abstract

Background. There are no studies reported on the pharmacokinetics of controlled release morphine (MST) in patients with hepatocellular carcinoma, the fifth most common cancer in the world.

Methods. We have studied the pharmacokinetic profile of MST (30 mg) in 15 patients with liver carcinoma (eight with primary carcinoma on top of chronic hepatitis C, and seven with secondary metastatic liver malignancy as a result of other primary) compared with our previously published data for 10 healthy controls. Plasma morphine concentrations were measured in venous blood samples at intervals up to 12 h by high-pressure liquid chromatography. Total body clearance (Cl) and systemic bioavailability were estimated using a compartmental method.

Results. Morphine bioavailability showed a substantial increase in patients with primary liver and secondary metastatic carcinoma than that of controls (64.8, 62.1, and 16.8%, respectively). The area under the serum concentration-time curve increased 4-fold in primary carcinoma (416 [SEM 25] µg h-1 litre-1) and 3-fold (303 [21] µg h-1 litre-1) in metastatic liver patients compared with healthy control (92.5 [3] µg h-1 litre-1). No significant difference was found in Tmax between the two malignant groups but Cmax was significantly greater in primary liver carcinoma patients. Impaired morphine elimination was noted in primary carcinoma only (t1/2 5.99 [0.39] h).

Conclusion. Careful administration of morphine is recommended in patients with liver cancer.

Keywords: analgesics opioid, morphine; drug deliver, oral; liver, disease; pharmocokinetics, morphine; pharmacology, morphine.
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Pharmacokinetics of controlled release morphine (MST) in patients with liver carcinoma
Johannes H. Proost
British Journal of Anaesthesia, 7 Feb 2005 [Full text]

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