Summary
The steady-state kinetics of morphine given as tablets and solution were compared in 7 cancer patients with chronic pain. There was no accumulation of morphine (20–40 mg) when repeatedly administered every 4 to 6 h. The mean steady-state concentration of morphine during the dose interval varied between 5.9 and 68.4 ng/ml (20.7–240 nmol/l), and was linearly related to the daily dose of morphine. There were no significant differences between the tablets and the solution of morphine with regard to relative oral bioavailability or peak concentration. The time-to-maximum plasma concentrations was significantly longer for the tablets. The pain score profile, assessed by a visual analogue scale during a dose interval, showed a similar pattern after the two oral formulations of morphine. No significant linear relationship between the scores and the plasma concentrations of morphine was observed.
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References
Aherne GW, Piall EM, Twycross RG (1979) Serum morphine concentration after oral administration of diamorphine hydrochloride and morphine sulphate. Br J Clin Pharmacol 8: 577–580
Aitken RCB (1969) Measurement of feelings using visual analogue scales. Proc Roy Soc Med 62: 989–993
Beaver WT (1981) Measurement of analgesic efficacy in man. Pain [Suppl 1]: 4
Berkowitz BA, Ngai SH, Yang JC, Hampstead J, Spector S (1975) The disposition of morphine in surgical patients. Clin Pharmacol Ther 17: 629–635
Brunk SF, Delle M (1974) Morphine metabolism in man. Clin Pharmacol Ther 16: 51–57
Dahlström B, Paalzow L (1975) Quantitative determination of morphine in biological samples by gasliquid chromatography and electronic capture detection. J Pharm Pharmacol 27: 172–176
Dahlström B, Paalzow L, Segre G, Ögren A (1978) Relation between morphine pharmacokinetics and analgesia. J Pharmacokinet Biopharm 6: 41–53
Dahlström B, Paalzow L (1978) Pharmacokinetic interpretation of the enterohepatic recirculation and first-pass elimination of morphine in the rat. J Pharmacokinet Biopharm 6: 505–519
Dahlström B, Bolme P, Feychting H, Noack G, Paalzow L (1979) Morphine kinetics in children. Clin Pharmacol Ther 26: 354–365
Dahlström B, Tamsen A, Paalzow L, Hartwig P (1982) Patient-controlled analgesic therapy IV: Pharmacokinetics and analgesic plasma concentrations of morphine. Clin Pharmacokinet 7: 266–279
Houde RN, Wallenstein SL, Beaver WT (1965) Clinical measurement of pain. In: de Stevens G (ed) Analgetics. Academic Press, New York, pp 75–122
Iwamoto K, Klaassen CD (1977) First-pass effect of morphine in rats. J Pharmacol Exp Ther 200: 236–244
Laidlaw MB, Read AE, Sherlock S (1961) Morphine tolerance in hepatic cirrhosis. Gastroenterology 40: 389–396
Littlejohns DW, Vere DW (1981) The clinical assessment of analgesic drugs. Br J Clin Pharmacol 11: 319–332
Melzack R, Mount BM, Gorden JM (1979) The Bromton mixture versus morphine solution given orally: Effects on pain. Can Med Assoc J 120: 435–438
Neal EA, Meffin PJ, Gregory PB, Blaschke TF (1979) Enhanced bioavailability and decreased clearance of analgesics in patient with cirrhosis. Gastroenterology 77: 96–102
Patwardhan RW, Johnsson RF, Hoyumpa A, Sheean JJ, Desmond PW, Wilkinson GR, Branch RA, Schenker S (1981) Normal metabolism of morphine in cirrhosis. Gastroenterology 81: 1006–1011
Saunders CM (1976) The challenge of terminal care. In: Symington T, Carter RL (eds) Scientific Foundations of Oncology, Heinemann, London, pp 673–679
Svensson JO, Rane A, Säwe J, Sjöqvist F (1982) Determination of morphine, morphine-3-glucuronide and (tentatively) morphine-6-glucuronide in plasma and urine using ion-pair high-performance liquid chromatography. J Chromatogr 280: 427–432
Säwe J, Dahlström B, Paalzow L, Rane A (1981) Morphine kinetics in cancer patients. Clin Pharmacol Ther 30: 629–635
Säwe J, Rane A, Svensson JO (1982) Morphine metabolism in cancer patients is independent of dose and duration of treatment. Br J Clin Pharmacol 14: 6228
Twycross RG (1974) Clinical experience with diamorphine in advanced malignant disease. Int J Clin Pharmacol 9: 184–198
Twycross RG (1979) Effect of cocaine in the brompton cocktail. In: Bonica J et al (ed) Advances in pain research and therapy, Volume 3, Raven Press, New York, pp 927–932
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Säwe, J., Dahlström, B. & Rane, A. Steady-state kinetics and analgesic effect of oral morphine in cancer patients. Eur J Clin Pharmacol 24, 537–542 (1983). https://doi.org/10.1007/BF00609900
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DOI: https://doi.org/10.1007/BF00609900