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

Abstract

We have studied the kinetic profile of controlled release morphine (MST) in 12 patients with posthepatitic cirrhosis, caused by HCV and HBsAg, with portal hypertension, given MST 30 mg for endoscopic sclerotherapy and compared the data with those from 10 healthy controls. Plasma drug concentrations were measured in venous blood samples at intervals up to 12 h by high-pressure liquid chromatography (HPLC). Total body clearance (Cl) and systemic availability were estimated using a compartmental method. Patients with cirrhosis had less clearance (0.586 litre h-1) than controls (0.729 litre h-1). Mean residence time (MRT) was prolonged in cirrhotic patients (19.57 h) compared with controls (7.03 h). Elimination half-life in cirrhotic patients (mean 7.36 (SEM 0.45) h) was nearly twice that of controls (4.01 (0.15) h). Serum concentrations were higher at all sampling times in the cirrhotic patients (peak concentration 35.2 (3.2) ng ml-1 compared with 12.8 (0.4) ng ml-1 in controls). For these changes in the kinetic profile of morphine (as MST) in cirrhotic patients, who experienced more sedation than controls, a smaller dose study together with longer dosing intervals is recommended.

Morphine or Oxycodone in Cancer Pain?

“…The role of oxymorphone in the total analgesic effect of oxycodone is, however, not yet clear. Liver dysfunction affects the metabolism of both oxycodone and morphine by increasing the elimination halflife and reducing plasma clearance (25,26). In kidney failure, oxycodone elimination is prolonged because of increased volume of distribution and reduced clearance (27).…”

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

“…Derived kinetic variables in control healthy volunteers have been published and fitted closely to other reported data. 6 Patients with liver cancer showed a 3-4-fold increase in the peak concentration of morphine presumably as a result of the reduction in first pass metabolism secondary to a reduction in liver cell mass; this led to an increase in total systemic Table 1 The pharmacokinetic values of oral MST 30 mg tablets in the control, primary and secondary liver cancer patients. a,b Significant difference (P<0.05) with the control and between the two cancer groups, respectively.…”

“…They all had normal renal and liver function with negative tests for hepatitis. 6 Administration of morphine was started at 10:00 in all patients. A cannula was inserted into an antecubital vein under local anaesthesia to facilitate sampling of venous blood.…”

Palliation and Liver Failure: Palliative Medications Dosage Guidelines

“…10 More recent studies have found a decreased plasma clearance and prolonged elimination half-life in patients with cirrhosis, compared to control patients without liver disease, therefore necessitating a reduction in dosage. 11,12 Pharmacokinetics of controlled release morphine in normal subjects and cirrhotic patients have been studied by Kotb et al, 13 and they found that the elimination half-life and total body clearance were significantly altered in the latter group. This suggests that accumulation is more likely to occur in patients with liver failure, with increased risk of opioid toxicity and the recommendations have been to decrease frequency of administration.…”