Heterogeneity of CYP3A isoforms metabolizing erythromycin and cortisol

@article{Hunt1992HeterogeneityOC,
  title={Heterogeneity of CYP3A isoforms metabolizing erythromycin and cortisol},
  author={Christina M. Hunt and Paul B. Watkins and Paul V. Saenger and Gregg M. Stave and Neal Barlascini and Charles O. Watlington and J. T. Wright and Philip S. Guzelian},
  journal={Clinical Pharmacology \& Therapeutics},
  year={1992},
  volume={51}
}
The N‐demethylation of erythromycin and 6β‐hydroxylation of Cortisol are both functions of the glucocorticoid‐inducible CYP3A in human liver microsomes. To determine whether 6β‐hydroxylation and erythromycin N‐demethylation are catalyzed by similar or distinct CYP3A isoforms, erythromycin N‐demethylase activity, as reflected by the recently described 14[C]‐erythromycin breath test, was compared with urinary 6β‐hydroxycortisol/cortisol ratios, a measure of Cortisol 6β‐hydroxylase activity, in… 
View on Wiley
deepblue.lib.umich.edu
121 Citations
Highly Influential Citations
2
Background Citations
20
Methods Citations
1
Results Citations
2

121 Citations

Absence of correlations among three putative in vivo probes of human cytochrome P4503A activity in young healthy men

No statistically significant correlations were observed among any of the trait measurements, and the reason(s) is unknown; however, it is possible that factors such as route of administration and extrahepatic metabolism in the intestinal epithelium and kidney are involved.

Differences in the Urinary Excretion of 6‐β‐Hydroxycortisol/Cortisol between Asian and Caucasian Women

Large intersubject and intrasubject variations of the 6‐β‐hydroxycortisol/ cortisol ratios were observed during the menstrual cycles in both ethnic groups, suggesting that Asian women may have a lower CYP3A activity compared with Caucasian women.

Neither dapsone hydroxylation nor cortisol 6β-hydroxylation detects the inhibition of CYP3A4 by HIV-1 protease inhibitors

These in vivo assays used to probe CYP3A4 activity are suboptimal, most likely because of the presence of extrahepatic sites of metabolism for both daps one and cortisol, and multiple CYP isozymes involved in dapsone N-hydroxylation.

Identification of the human P450 enzymes involved in the in vitro metabolism of the synthetic steroidal hormones Org 4060 and Org 30659

Measurements of kinetic parameters of P450 enzymes that could metabolize both steroids, combined with the fact that CYP3A4 is known to be the most abundant P450 enzyme in the human liver, indicate that CYC3A 4 will be of major importance for the in vivo human metabolism of Org 4060 and Org 30659.

Cortisol metabolism in vitro—III. Inhibition of microsomal 6β—hydroxylase and cytosolic 4-ene-reductase

  • S. M. AbelD. Back
  • Biology, Chemistry
    The Journal of Steroid Biochemistry and Molecular Biology
  • 1993

Effect of Multiple Doses of Rifampin on the [14C N‐methyl] Erythromycin Breath Test in Healthy Male Volunteers

The reproducibility of the EBT was evaluated in eight healthy volunteers before and after oral administration of 600 mg of rifampin daily for 8 days and results support the utility of EBT as a valid, reproducible, and reliable measure of CYP3A activity in vivo.

Effect of age and gender on the activity of human hepatic CYP3A.

Correlation between docetaxel clearance and estimated cytochrome P450 activity by urinary metabolite of exogenous cortisol.

The interpatient variability of CYP3A4 activity and docetaxel CL could be predicted by measuring T6beta-OHF after cortisol administration, a new method developed by measuring urinary cortisol metabolite after administration of exogenous cortisol.

Cortisol metabolism by human liver in vitro—I. Metabolite identification and inter-individual variability

Comparison of the dapsone recovery ratio and the erythromycin breath test as in vivo probes of CYP3A activity in patients with rheumatoid arthritis receiving cyclosporine

...

References

SHOWING 1-10 OF 29 REFERENCES

6β‐Hydroxycortisol in random urine samples as an indicator of enzyme induction

Random measurements of 6β‐OHF/FF ratios may be used to detect enzyme induction by drugs or disease and greatly simplifies noninvasive screening for enzyme induction.

Significance of cytochrome P-450 (P-450 HFLa) of human fetal livers in the steroid and drug oxidations.

Testosterone metabolism by cytochrome P-450 isozymes RLM3 and RLM5 and by microsomes. Metabolite identification.

Human liver microsomal steroid metabolism: identification of the major microsomal steroid hormone 6 beta-hydroxylase cytochrome P-450 enzyme.

Urinary Excretion of 6β-Hydroxycortisol in States of Altered Thyroid Function

Administration of cortisol resulted in a marked increase of urinary 6β-hydroxycortisol excretion in myxedematous subjects to a greater extent than in hyperthyroid and control subjects.

Regioselectivity and stereoselectivity of androgen hydroxylations catalyzed by cytochrome P-450 isozymes purified from phenobarbital-induced rat liver.

Identification of an inducible form of cytochrome P-450 in human liver.

It has not yet been determined whether human liver contains inducible cytochromes P-450 similar to those that catalyze the oxidative metabolism of foreign substances in animals. We carried out…

Corticosterone is converted to 6 beta-hydroxycorticosterone in rat: effects of the metabolite on urinary electrolyte excretion.

Regulation of rat hepatic cytochrome P-450: age-dependent expression, hormonal imprinting, and xenobiotic inducibility of sex-specific isoenzymes.

Investigation of the influence of age, sex, and hormonal status on the expression of eight rat hepatic cytochrome P-450 (P-450) isoenzymes established that the response of these latter five isoenZymes to the P- 450 inducers phenobarbital, beta-naphthoflavone, pregnenolone-16 alpha-carbonitrile, and isosafrole is qualitatively and quantitatively equivalent in females as in males.

Identification of the rabbit and human cytochromes P-450IIIA as the major enzymes involved in the N-demethylation of diltiazem.

Investigation ofOxidative metabolism of diltiazem (DTZ), a calcium channel blocker, was investigated in rabbit and human liver microsomes as well as in primary cultures of human hepatocytes, consistent with the view that in both rabbit andhuman, cytochromes P-450 from the P- 450IIIA subfamily are the major enzymes involved in the N-demethylation of DTZ.