A sensitive ELISA for 6β-hydroxycortisol in urine using enzyme penicillinase (β-lactamase)

This study was carried out to investigate whether minute quantities of maternal drugs ingested over an extended period of time by a breast-feeding infant can alter the activity pattern of the infant's hepatic drug metabolizing enzyme (HDME). The HDME activity patterns of 12 breast-fed infants whose mothers were not on drug therapy were compared with those of 11 infants whose mothers had been taking 30 micrograms levo-norgesterel daily for 90 to 195 days (oral contraceptives group) and of 10 infants whose mothers had been taking ethambutol and isoniazid daily since pregnancy (tuberculosis group). As 6 beta hydroxycortisol in urine is considered to be a good and acceptable reflector of HDME activity, it was estimated from the infants' urine using enzyme-linked immunosorbent assay (ELISA) technique. A comparison of the patterns between 90 days of age and 195 days of age of the infants in the control group and the two study groups indicated an increase from 36.6 ng/mL to 58.4 ng/mL at 195 days in the control group. An initial decrease from 36.6 ng/mL to 26.2 ng/mL was noted with commencement of maternal levo-norgesterel therapy, followed by a slow and steady rise to 47.8 ng/mL at 195 days of age, with a shift in the peak from 120 to 135 days of infants age in the oral contraceptive group. A suppressed pattern with decreased levels of 6 beta hydroxycortisol ranging from 19.3 ng/mL to 26.5 ng/mL at 195 days was found in the tuberculosis group. The data were analyzed by two-way analysis of variance (ANOVA) coupled with Duncan's Multiple range test. Both treatment group showed significant differences from the control group at the 0.050 level. The HDME plays an important role in determining the final outcome of any drug in humans, as it controls the metabolism of drugs. Hence, alterations in its activity caused by the transfer of maternal drugs over a prolonged period of time could pose a serious problem to nurslings when they require drugs for their own benefit.

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Can Chronic Maternal Drug Therapy Alter the Nursing Infant's Hepatic Drug Metabolizing Enzyme Pattern?

Toddywalla

Patel

Betrabet

et al. 1995

The Journal of Clinical Pharma

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Urinary 6?-hydroxycortisol: a validated test for evaluating drug induction or drug inhibition mediated through CYP3A in humans and in animals

Galteau

Shamsa

2003

European Journal of Clinical Pharmacology

145

116

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6beta-Hydroxycortisol (6beta-OHF) urinary excretion has, for a long time, been considered a marker of drug induction and, more recently, of drug inhibition in humans and in laboratory animals, but its specificity is still under debate. In this work, we review 277 papers devoted to 6beta-OHF urinary excretion. We have evaluated factors that could modify 6beta-OHF excretion and, thus, could explain contradictory results. We have examined the effect of the analytical techniques on physiological values. Intra- and inter-individual variability and the effect of circadian rhythms on urinary excretion of 6beta-OHF as well as cortisol and 17-hydroxycorticosteroids have been evaluated. We also give an overview of drugs that induce, inhibit or have no effect on 6beta-OHF. For inducing and inhibiting drugs, we calculated the ranges of variation of 6beta-OHF excretion from the results indicated in the different papers. This work was done for well-known inducers, such as anticonvulsants, but also for other inducing or inhibiting drugs found in the literature. The time-course of variation in 6beta-OHF excretion when different drugs are co-administered was also investigated. The potential relationship between cytochrome P(450) 3A4 (CYP3A4) polymorphism and 6beta-OHF excretion was studied. Finally, the interest of 6beta-OHF urinary excretion was compared with that of other tests proposed to measure CYP3A4 activity. This review demonstrates that 6beta-OHF urinary excretion is a good test to evaluate drug-metabolising enzyme inducing or inhibiting properties of drugs when the subjects are their own controls, but this test is not reliable enough to measure actual CYP3A4 activity.

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An efficient enzymatic preparation of 20-pregnane succinates: chemoenzymatic synthesis of 20β-hemisuccinyloxy-5αH-pregnan-3-one

et al. 2008

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This article was published in an Elsevier journal. The attached copy is furnished to the author for non-commercial research and education use, including for instruction at the author's institution, sharing with colleagues and providing to institution administration. Other uses, including reproduction and distribution, or selling or licensing copies, or posting to personal, institutional or third party websites are prohibited. In most cases authors are permitted to post their version of the article (e.g. in Word or Tex form) to their personal website or institutional repository. Authors requiring further information regarding Elsevier's archiving and manuscript policies are encouraged to visit: http://www.elsevier.com/copyright

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A sensitive ELISA for 6β-hydroxycortisol in urine using enzyme penicillinase (β-lactamase)

Cited by 6 publications

References 16 publications

Can Chronic Maternal Drug Therapy Alter the Nursing Infant's Hepatic Drug Metabolizing Enzyme Pattern?

Can Chronic Maternal Drug Therapy Alter the Nursing Infant's Hepatic Drug Metabolizing Enzyme Pattern?

Urinary 6?-hydroxycortisol: a validated test for evaluating drug induction or drug inhibition mediated through CYP3A in humans and in animals

An efficient enzymatic preparation of 20-pregnane succinates: chemoenzymatic synthesis of 20β-hemisuccinyloxy-5αH-pregnan-3-one

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