C Broen Christensen

Publications (3)7.88 Total impact

• Article: Impact of quinidine on plasma and cerebrospinal fluid concentrations of codeine and morphine after codeine intake.

  S H Sindrup, U Hofmann, J Asmussen, G Mikus, K Brøsen, F Nielsen, S H Ingwersen, C Broen Christensen
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  ABSTRACT: The analgesic effect of codeine depends on its O-demethylation to morphine via sparteine oxygenase (CYP2D6) in the liver and presumably also via this enzyme in the CNS. We studied the ability of quinidine, which is a potent inhibitor of CYP2D6, to penetrate the blood brain barrier and its possible impact on codeine O-demethylation in CNS. The study comprised 16 extensive and one poor metaboliser of sparteine, who underwent spinal anaesthesia for urinary tract surgery or examination. Eight patients were given an oral dose of 125 mg codeine and 9 patients (including the poor metaboliser) were given 200 mg quinidine 2 h before the same dose of codeine. Plasma and spinal fluid samples were collected 2 h after codeine intake. Free concentrations of quinidine were 11-times lower in cerebrospinal fluid than in plasma, and ranged from 9-15 nmol.l-1. Morphine concentrations were significantly lower in patients pre-treated with quinidine, both in plasma (median 1.45 nmol.l-1, range 0.74-1.95 nmol.l-1 vs 9.86 nmol.l-1, range 4.59-28.4 nmol.l-1) and in cerebrospinal fluid (0.23, 0.16-0.61 nmol.l-1 vs 3.63, 0.6-8.09 nmol.l-1). The morphine/codeine concentration ratio in plasma (3.07 x 10 (-3), 1.68-3.68 x 10 (-3) vs 19.87 x 10 (-3), 9.87-66.22 x 10 (-3) and in cerebrospinal fluid (0.83 d 10 (-3), 0.58-1.45 x 10 (-3) vs 7.19 x 10 (-3), 2.03-17.7 x 10 (-3) was also lower. The morphine/codeine concentration ratios were significantly lower in cerebrospinal fluid both without and with quinidine, but the difference between the plasma and spinal fluid ratio was significantly smaller with quinidine than without (p = 0.0002). Quinidine penetrates the blood brain barrier poorly, but quinidine pre-treatment leads to pronounced lowering of the cerebrospinal fluid concentration of morphine after codeine intake. However, the O-demethylation of codeine in CNS may not be totally blocked by quinidine.
  European Journal of Clinical Pharmacology 02/1996; 49(6):503-9. · 2.85 Impact Factor
• Article: Comparative bioavailability of a morphine suppository given rectally and in a colostomy.

  J Højsted, K Rubeck-Petersen, H Rask, D Bigler, C Broen Christensen
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  ABSTRACT: In eight patients with a colostomy, plasma morphine levels were followed for 8 h after administration of 20 mg morphine chloride as a suppository, first rectally and after at least 48 h via the colostomy. The bioavailability after administration in the colostomy showed very great variation; the mean value compared to rectal bioavailability was only 43% (range 0.1-127%). In four patients the plasma concentrations of morphine after colostomy administration were lower at all times than after rectal administration, and in three only small amounts of morphine were detectable. One patient showed higher plasma concentrations after colostomy application than after rectal administration. It is concluded that administration of morphine suppositories in a colostomy cannot be recommended.
  European Journal of Clinical Pharmacology 02/1990; 39(1):49-50. · 2.85 Impact Factor
• Article: Excretion of morphine in human breast milk.

  V L Feilberg, D Rosenborg, C Broen Christensen, J V Mogensen
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  ABSTRACT: Five lactating women who underwent surgery and were treated with morphine epidurally or IV/IM in the postoperative phase were included in the study. The morphine concentrations in plasma and breast milk were determined 0, 15, 30, 45, 60, 90, 120, 240, 360 and 480 min after drug administration by means of a specific radioimmunoassay for morphine. The milk-to-plasma ratio was 2.45 +/- 0.8 (mean +/- s.d.). The amount of morphine transferred by nursing is, even at the peak concentration of 500 ng/ml milk, small and will hardly cause respiratory depression or drowsiness in the child.
  Acta Anaesthesiologica Scandinavica 08/1989; 33(5):426-8. · 2.19 Impact Factor