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

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 [sem25] microg h(-1) litre(-1)) and 3-fold (303 [21] microg h(-1) litre(-1)) in metastatic liver patients compared with healthy control (92.5 [3] microg h(-1) litre(-1)). No significant difference was found in T(max) between the two malignant groups but C(max) was significantly greater in primary liver carcinoma patients. Impaired morphine elimination was noted in primary carcinoma only (t(1/2) 5.99 [0.39] h). CONCLUSION: Careful administration of morphine is recommended in patients with liver cancer.

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

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.

Colorimetric determination of theophylline and aminophylline with diazotized p-nitroaniline.

The reactions of theophylline and aminophylline with diazotized p-nitroaniline in alkaline medium have been studied and developed into a sensitive assay for both drugs. The yellow azo-dyes formed with theophylline and aminophylline show maximum absorption at 440 and 410 nm respectively. Beer's law is valid within the concentration range 2-16 mug/ml for theophylline and 1-8 mug/ml for aminophylline. All variables which affect the reactions were studied and optimized. The proposed method has been successfully applied to determination of the drugs in their commercially available dosage forms. Statistical analysis of the results revealed that the proposed method is as precise and accurate as the official USP procedure.