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  • antipyrine  (2)
  • haem biosynthesis  (2)
  • 1
    Digitale Medien
    Digitale Medien
    Springer
    European journal of clinical pharmacology 35 (1988), S. 241-247 
    ISSN: 1432-1041
    Schlagwort(e): carbamazepine ; porphyria ; epilepsy ; haem biosynthesis ; enzyme induction
    Quelle: Springer Online Journal Archives 1860-2000
    Thema: Chemie und Pharmazie , Medizin
    Notizen: Summary The anticonvulsant drug carbamazepine has been reported to produce a condition clinically and biochemically similar to acute intermittent porphyria (AIP). We have determined the effect of chronic carbamazepine treatment on the activities of the enzymes of haem biosynthesis in circulating blood cells and on the urinary excretion of porphyrins and their precursors in 53 epileptic patients receiving monotherapy and in 42 age- and sex-matched controls. In the patients the mean activity of leucocyte 5-aminolaevulinic acid (ALA) synthase, the rate-limiting enzyme of the pathway, was 218% of control values (p〈0.001) and ALA-dehydratase activity was reduced by 37% (p〈0.001). Circulating carbamazepine concentrations correlated negatively with ALA dehydratase (r s=−0.45;p〈0.01). Porphobilinogen deaminase and uroporphyrinogen decarboxylase appeared unaffected by carbamazepine treatment. Significant quantitative increases in the urinary excretion of porphobilinogen and total porphyrins (bothp〈0.05) accompanied the changes in enzyme activity. Similar dose-dependent effects on ALA synthase and ALA dehydratase were shown to occur in rats treated for 5 days with 3 different doses of carbamazepine. These findings further support the porphyrinogenicity of carbamazepine, but the pattern of enzyme alteration differs from that found in AIP.
    Materialart: Digitale Medien
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  • 2
    Digitale Medien
    Digitale Medien
    Springer
    European journal of clinical pharmacology 21 (1981), S. 155-160 
    ISSN: 1432-1041
    Schlagwort(e): rifampicin ; antipyrine ; 3-hydroxymethylantipyrine ; 4-hydroxyantipyrine ; norphenazone ; cytochrome P-450
    Quelle: Springer Online Journal Archives 1860-2000
    Thema: Chemie und Pharmazie , Medizin
    Notizen: Summary Antipyrine is oxidised to three main metabolites in man. There is evidence that the different metabolites are products of different forms of cytochrome P-450. The effect of rifampicin administration for two weeks on the rates of formation of these metabolites was investigated in healthy volunteers. Rifampicin increased antipyrine clearance and shortened its half-life. Two weeks after stopping rifampicin the induction had largely been reversed. Clearance to all three metabolites was increased by rifampicin. Clearance to 3-hydroxymethylantipyrine was increased from 7.8±0.9 ml/min to 13.3±1.3 ml/min, to norphenazone from 5.8±0.6 ml/min to 19.3±2.1 ml/min and to 4-hydroxyantipyrine from 14.3±2.2 ml/min to 21.9±3.9 ml/min. Thus clearance to norphenazone was increased to a much greater extent than to either of the other two metabolites. It is concluded that this provides evidence for the involvement of at least two different forms of cytochrome P-450 in antipyrine metabolism in man.
    Materialart: Digitale Medien
    Bibliothek Standort Signatur Band/Heft/Jahr Verfügbarkeit
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  • 3
    Digitale Medien
    Digitale Medien
    Springer
    European journal of clinical pharmacology 26 (1984), S. 453-456 
    ISSN: 1432-1041
    Schlagwort(e): carbamazepine ; thyroid hormones ; antipyrine ; enzyme induction
    Quelle: Springer Online Journal Archives 1860-2000
    Thema: Chemie und Pharmazie , Medizin
    Notizen: Summary The effect of short-term hepatic enzyme induction with carbamazepine (CBZ) on circulating thyroid hormone concentrations was studied in 10 healthy male subjects. CBZ 400 mg per day was given for 21 days in 6 subjects and for 14 days in a further 4. In the former group the effect of therapy on the pituitary/thyroid axis was also assessed by measuring thyroid stimulating hormone (TSH) response to thyrotrophin-releasing hormone. CBZ therapy resulted in induction of hepatic monooxygenase activity, evidenced by a fall in antipyrine half-life (11.1±0.7 to 7.6±0.7 h; p〈0.001), and a rise in antipyrine clearance (0.72±0.06 to 0.98±0.1 ml min−1 kg−1; p〈0.001). A significant fall in total serum thyroxine (T4) (81.9±2.9 to 75.1±2.9 nmol l−1), and triiodothyronine (T3); (1.59±0.07 to 1.37±0.05 nmol l−1) and free T4 (16.03±0.82 to 14.2±0.8 pmol l−1) was seen after CBZ therapy. (all p〈0.05). No significant change in reverse T3 or thyroid binding globulin occurred. In the 6 subjects studied for 21 days, maximal changes were found following 14 days' treatment. Basal and stimulated TSH remained unaltered. These effects on circulating thyroid hormone concentrations are likely to be secondary to hepatic enzyme induction leading to accelerated nondeiodinative hepatic hormone disposal. The reason for the failure of pituitary TSH secretion to rise in response to the fall in circulating T4 and T3 is unclear but may have implications for chronic treatment with CBZ in epileptic patients.
    Materialart: Digitale Medien
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  • 4
    ISSN: 1432-1041
    Schlagwort(e): stanozolol ; porphyria ; aplastic anaemia ; anabolic steroids ; haem biosynthesis ; monooxygenases ; cytochrome P 450 ; vascular thrombosis
    Quelle: Springer Online Journal Archives 1860-2000
    Thema: Chemie und Pharmazie , Medizin
    Notizen: Summary Stanozolol is an anabolic steroid which is used in the treatment of aplastic anaemia and has been recently advocated for the prophylaxis of vascular thrombosis. Similar steroid substances stimulate the activity of δ-aminolaevulinic acid synthase (ALA S), the rate limiting enzyme of haem biosynthesis, in rat hepatocytes and chick embryo liver cell cultures and activate acute hepatic porphyria. In the present study stanozolol (10 mg daily for 14 days) has been shown to increase significantly leucocyte ALA S activity in 9 healthy male subjects. There was a concomitant rise in urinary ALA and total porphyrin excretion but no change in antipyrine kinetics or urinary 6 B hydroxycortisol excretion. In a complementary study in male Sprague Dawley rats, stanozolol administered intraperitoneally, produced a dose-dependent increase in hepatic ALA S activity without changing hepatic cytochrome P 450 content. Stanozolol has been clearly shown to elevate ALA S activity, probably directly, and, thereby, porphyrin production without affecting hepatic monooxygenase activity. This porphyrinogenic effect may be relevant to the successful treatment of aplastic anaemia with anabolic steroids. Leucocyte ALA S activity may provide a human system for the study of drug porphyrinogenicity in vivo.
    Materialart: Digitale Medien
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