Sep 27, 1980 - Oral and intravenous morphine kinetics were studied in seven patients ... continuous treatment with morphine because of severe chronic pain.
Morphine kinetics in cancer patients Oral and intravenous morphine kinetics were studied in seven patients with cancer who needed continuous treatment with morphine because of severe chronic pain. Single oral (20 to 30 mg) and intravenous (4 mg) doses were given on separate days, followed by repetitive blood sampling for morphine analysis by gas chromatography. Volume of distribution ranged train 0.95 to 3.75 1/kg and serum clearance from 5.0 to /6.1 mIlminIkg. Oral morphine in doses that were more than Jive times the intravenous dose gave concentrations (at 10 and 120 min after dose) between 38 and 112 nglml. During the 0.25- to 8-hr period utter the oral dose Ser1/111 concentrations were higher than after the intravenous dose. There was a variation in oral bioavailability of 15% to 64% and an interindividual variation in terminal half-life from 58 to 467 min. These data warrant careful adjustment of the oral dose under close supervision of the patient at the onset of therapy.
J. Sawe, M.D., B. Dahistresm, Ph.D.,* L. Paalzow, Ph.D.,** and A. Rane, M.D. Solna and Huddinge, Sweden Central Research and Control Laboratory of the National Corporation of Swedish Pharmacies, Solna, and Department of Clinical Pharmacology, Karolinska Institute, Huddinge Hospital, Hiiddinge
Morphine has long been used parenterally for treatment of severe chronic pain in patients with advanced malignant disease."' 18 Oral preparations of opiates have been used in a limited number of countries on an empirical basis" and have gained considerable interest in Sweden over the past few years.8 Data on morphine kinetics are available in healthy subjects and surgical patients2. 3' 6' 16' 17 but not in patients with advanced malignant disease, in whom catabolism and organ metastases may alter drug disposition. We have investigated morphine kinetics after This study was supported by grants I4X-05677 and 04-03902 from the Swedish Cancer Society and Swedish Medical Research Council. Received for publication Sept. 27, 1980.
Accepted for publication Aug. 15, 1981. Reprint requests to: Dr. A. Rane, Department of Clinical Pharmacology, Karolinska Institute, Huddinge Hospital, S-14I 86, Huddinge, Sweden.
0009-9236/81/110629+07$00.70/0 ©
oral and intravenous doses to establish a kinetic basis for the rational use of morphine in cancer patients with severe pain. To our knowledge, no direct assessment has been published on the kinetics (including bioavailability) of oral morphine in such patients. Patients and methods
Our subjects were seven patients with advanced malignant diseases of differing types. Five were women, two men. Ages varied from 49 to 79 years. Clinical and blood chemistry data are given in Tables I and II. Two subjects were icteric. They had been admitted to the hospital for causal and palliative treatment. Most of the patients were treated with single doses of narcotic analgesics other than morphine during a short period before the study began. Design of the study. Four milligrams of morphine (the HC1 in all cases), corresponding
1981 The C. V. Mosby Co.
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Clin. Pharmacy!. Ther.
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Table I. Clinical characteristics (y. the patients Patient No.
Age/sex/weight
Tumor location
59/F/50
Kidney; bone metastases Pancreas: hepatic metastases
2
60/F/46
3
56/F/52
4
76/F/65
5
59/M/82
6
69/M/53
7
49/F/62
Current medication
Methenamine
Levothyroxine, cephalexin, amoxicillin, bromhexine
tu-5-Fluorouracil, prochlor-
Colon; local mor growth Unknown origin: hepatic metastases
perazine
tu-Prochlorperazine Ductus choledo-Vitamin K Lung; local mor growth
chus; icteric Vesica fellea: teric
ic-Prochlorperazine
Table II. Laboratory data (normal ranges in our hospital in parentheses) Albumin Patient No. 1
2 3
4 5
6 7
ASAT
ALAT
ALP
-y-GT
Bile acid
(
