Abstract
The mean plasma half-life (T 1 2) of antipyrine was prolonged (21.69 ± 1.92 hr) in a group of 10 patients with hereditary hepatic porphyria, 8 of whom had acute intermittent porphyria (AIP) confirmed by decreased erythrocyte uroporphyrinogen-l-synthetase (URO-S) activities and 2 of whom had mixed hepatic porphyria, in comparison to the mean of 20 normal control subjects (12.65 ± 0.86 hr, p < 0.01). Antipyrine T 1 2 was especially prolonged in patients with a history of more severe symptoms, but there was no correlation with the degree of elevation in urinary excretion of the porphyrin precursors δ-aminolevulinic acid (ALA) and porphobilinogen (PBG). In 7 completely latent carriers of the AIP gene defect who had normal urinary ALA and PBG levels, the elimination rates of antipyrine from plasma were entirely normal. Phenylbutazone T 1 2s were normal 10 porphyric patients tested. These results demonstrate that the cytochrome P-450-dependent enzyme system for oxidizing antipyrine, but not that for phenylbutazone, is impaired in some AIP individuals in whom the gene defect for the disorder is clinically expressed and that this impairment may be related to the severity of the disease. The partial decrease in URO-S activity characteristic of AIP does not result in a profound or generalized decrease in hepatic cytochrome P-450 function, however, even when there is sufficient derangement in the hepatic heme biosynthetic pathway to lead to excessive excretion of chemical intermediates in the pathway.
| Original language | English (US) |
|---|---|
| Pages (from-to) | 47-54 |
| Number of pages | 8 |
| Journal | Clinical Pharmacology and Therapeutics |
| Volume | 19 |
| Issue number | 1 |
| State | Published - Jan 1976 |
| Externally published | Yes |
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ASJC Scopus subject areas
- Pharmacology
Cite this
Studies in porphyria V. Drug oxidation rates in hereditary hepatic porphyria. / Anderson, Karl; Alvares, Alvito P.; Sassa, Shigeru; Kappas, Attallah.
In: Clinical Pharmacology and Therapeutics, Vol. 19, No. 1, 01.1976, p. 47-54.Research output: Contribution to journal › Article
}
TY - JOUR
T1 - Studies in porphyria V. Drug oxidation rates in hereditary hepatic porphyria
AU - Anderson, Karl
AU - Alvares, Alvito P.
AU - Sassa, Shigeru
AU - Kappas, Attallah
PY - 1976/1
Y1 - 1976/1
N2 - The mean plasma half-life (T 1 2) of antipyrine was prolonged (21.69 ± 1.92 hr) in a group of 10 patients with hereditary hepatic porphyria, 8 of whom had acute intermittent porphyria (AIP) confirmed by decreased erythrocyte uroporphyrinogen-l-synthetase (URO-S) activities and 2 of whom had mixed hepatic porphyria, in comparison to the mean of 20 normal control subjects (12.65 ± 0.86 hr, p < 0.01). Antipyrine T 1 2 was especially prolonged in patients with a history of more severe symptoms, but there was no correlation with the degree of elevation in urinary excretion of the porphyrin precursors δ-aminolevulinic acid (ALA) and porphobilinogen (PBG). In 7 completely latent carriers of the AIP gene defect who had normal urinary ALA and PBG levels, the elimination rates of antipyrine from plasma were entirely normal. Phenylbutazone T 1 2s were normal 10 porphyric patients tested. These results demonstrate that the cytochrome P-450-dependent enzyme system for oxidizing antipyrine, but not that for phenylbutazone, is impaired in some AIP individuals in whom the gene defect for the disorder is clinically expressed and that this impairment may be related to the severity of the disease. The partial decrease in URO-S activity characteristic of AIP does not result in a profound or generalized decrease in hepatic cytochrome P-450 function, however, even when there is sufficient derangement in the hepatic heme biosynthetic pathway to lead to excessive excretion of chemical intermediates in the pathway.
AB - The mean plasma half-life (T 1 2) of antipyrine was prolonged (21.69 ± 1.92 hr) in a group of 10 patients with hereditary hepatic porphyria, 8 of whom had acute intermittent porphyria (AIP) confirmed by decreased erythrocyte uroporphyrinogen-l-synthetase (URO-S) activities and 2 of whom had mixed hepatic porphyria, in comparison to the mean of 20 normal control subjects (12.65 ± 0.86 hr, p < 0.01). Antipyrine T 1 2 was especially prolonged in patients with a history of more severe symptoms, but there was no correlation with the degree of elevation in urinary excretion of the porphyrin precursors δ-aminolevulinic acid (ALA) and porphobilinogen (PBG). In 7 completely latent carriers of the AIP gene defect who had normal urinary ALA and PBG levels, the elimination rates of antipyrine from plasma were entirely normal. Phenylbutazone T 1 2s were normal 10 porphyric patients tested. These results demonstrate that the cytochrome P-450-dependent enzyme system for oxidizing antipyrine, but not that for phenylbutazone, is impaired in some AIP individuals in whom the gene defect for the disorder is clinically expressed and that this impairment may be related to the severity of the disease. The partial decrease in URO-S activity characteristic of AIP does not result in a profound or generalized decrease in hepatic cytochrome P-450 function, however, even when there is sufficient derangement in the hepatic heme biosynthetic pathway to lead to excessive excretion of chemical intermediates in the pathway.
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UR - http://www.scopus.com/inward/citedby.url?scp=0017260773&partnerID=8YFLogxK
M3 - Article
VL - 19
SP - 47
EP - 54
JO - Clinical Pharmacology and Therapeutics
JF - Clinical Pharmacology and Therapeutics
SN - 0009-9236
IS - 1
ER -