N‐demethylation of ethylmorphine in pregnant and non‐pregnant women and in men: an evaluation of the effects of sex steroids.

Gerdin, Eva; Rane, Anders

doi:10.1111/j.1365-2125.1992.tb04132.x

Cited by 14 publications

(6 citation statements)

References 15 publications

Supporting

Mentioning

Contrasting

Order By: Relevance

Section: Discussionsupporting

confidence: 82%

“…glucuronides) might have been recovered from faeces. Our urinary recovery of parent drug plus metabolites was almost twice as high as reported in a previous study [29]. This is probably due to determination of more metabolites and longer observation periods in the present study.…”

Section: Discussionsupporting

confidence: 69%

“…Previous studies have inferred formation of ethylmorphine-6-glucuronide indirectly, based on an increase in ethylmorphine after sample hydrolysis [4,29]. The finding of ten times more ethylmorphine-6-glucuronide than ethylmorphine in urine in the present study was in accordance with published indirect measurements [4,29]. In the present study urinary recoveries of morphine plus its 3-and 6-glucuronides constituted about 15%, and norethylmorphine after, hydrolysis about 9% of the dose, compared with 24 and 12% of the total urinary excretion products, respectively, reported by Rane et al [4].…”

Section: Discussionmentioning

confidence: 99%

See 2 more Smart Citations

Biotransformation and pharmacokinetics of ethylmorphine after a single oral dose.

Aasmundstad¹,

Xu²,

Johansson³

et al. 1995

Brit J Clinical Pharma

View full text Add to dashboard Cite

1 The pharmacokinetics of ethylmorphine after administration of a single dose of the cough mixture Cosylan® were investigated in 10 healthy subjects. 2 The median urinary recovery of ethylmorphine and measured metabolites was 77% over 48 h. The median tmax of unchanged ethylmorphine was 45 min, and the terminal elimination t'/2 was 2 h. Ethylmorphine-6-glucuronide was found to be the major metabolite. 3 Two subjects had significantly lower urinary recovery (0,48 h) of morphine and morphine-glucuronides than the remainder. Furthermore, these two had urinary metabolic ratios (MRO) and partial metabolic clearances (CLmo) for O-deethylation of ethylmorphine tentatively classifying them phenotypically as poor metabolisers of the debrisoquine/sparteine type. 4 Genotyping for cytochrome P450 (CYP) 2D6 alleles revealed five homozygote (wt/wt) and five heterozygote subjects. Two subjects phenotypically classified as poor metabolisers were genotypically CYP2D6A/wt and CYP2D6D/wt, respectively. 5 Serum and urine samples taken more than 8 and 24 h after administration of ethylmorphine respectively, contained morphine and morphine-glucuronides, but no ethylmorphine, ethylmorphine-6-glucuronide or (serum only) norethylmorphine. Norethylmorphine could be detected after hydrolysis of urine samples in all subjects. The urinary recovery of the active metabolites morphine and morphine-6-glucuronide after administration of ethylmorphine varied by a factor of 9 between individuals. 6 The wide variation in recovery of morphine and morphine-glucuronides after oral administration of ethylmorphine could not be explained simply by a difference in CYP2D6 genotype. Constitutional variation in other enzymatic pathways involved in ethylmorphine metabolism is probably crucial. Ratios of morphine to parent drug cannot be used to distinguish the source of morphine after administration of ethylmorphine. Norethylmorphine should be included in urine assays for opiates in forensic toxicology, and no firm conclusions about the source of morphine are possible based on serum samples obtained more than 24 h after drug administration.

show abstract

Section: Discussionsupporting

confidence: 82%

Section: Discussionsupporting

confidence: 69%

Section: Discussionmentioning

confidence: 99%

See 1 more Smart Citation

Biotransformation and pharmacokinetics of ethylmorphine after a single oral dose.

Aasmundstad¹,

Xu²,

Johansson³

et al. 1995

Brit J Clinical Pharma

View full text Add to dashboard Cite

show abstract

“…CYP2D6 activity in the menstrual cycle phases has been investigated by use of dextromethorphan, metoprolol, ethylmorphine, and debrisoquin (INN, debrisoquine) as substrates. Most of the studies have not detected differences between cycle phases, 48 , 49 , 50 , 51 although 1 study showed a small decrease in debrisoquin metabolic ratio (ie, higher activity) in the luteal phase 52 . CYP2D6 activity is higher during pregnancy 53 , 54 .…”

Section: Discussionmentioning

confidence: 99%

Influence of menstrual cycle on cytochrome P450 2A6 activity and cardiovascular effects of nicotine*

Hukkanen

Gourlay

Kenkare

et al. 2005

Clin Pharmacol Ther

View full text Add to dashboard Cite

show abstract

“…These investigators used the metabolism of midazolam to 1'-hydroxymidazolam as an indicator of cytochrome P4503A activity. Owing to overlapping substrate specificities, confusion exists as to which specific isozymes of the CYP3A subfamily may undertake this reaction, as is the case for Alfentanil no difference clearance [79] Alprazolam no difference clearance [80,81] Dextromethophan no difference clearance (N-demethylation) [75,82] Eletriptan no difference clearance [83] Ethylmorphine no difference N-demethylation [84] Midazolam no difference clearance [85,86] Midazolam increase follicular 1-hydroxylation [87] Omeprazole no difference sulphone formation [88] CYP3A4 b…”

Section: Cytochrome P450 Mediated Biotransforma-tionmentioning

confidence: 99%

The Menstrual Cycle and Drug Metabolism

Mitchell¹,

Smith²,

Waring³

2009

CDM

View full text Add to dashboard Cite

Within the field of drug metabolism, when addressing quantitative aspects, an average value is traditionally quoted, commonly the arithmetic mean with perhaps an indication of spread. Better still a range of values may be given, thereby acknowledging that various factors may precipitate differences between individuals. A single subject, however, usually only merits a single value. Nevertheless, events such as an acute illness or concurrent drug therapy serve to alert that this value may change substantially over a relatively short time-period, although any potential effects of naturally occurring phenomena, such as the female menstrual cycle, are often overlooked or disregarded. Are the biochemical and physiological changes that occur during the menstrual cycle able to influence xenobiotic metabolism? Is the idea of a stable and unwavering baseline within a single healthy individual flawed? Is it time to reassess our thinking with regards to such aspects? This brief review explores these issues and examines information available within the literature for evidence of potential influences of menstrual cycle events upon drug metabolism, defined as the actual chemical alteration of the parent molecule into another chemical species.

show abstract

N‐demethylation of ethylmorphine in pregnant and non‐pregnant women and in men: an evaluation of the effects of sex steroids.

Cited by 14 publications

References 15 publications

Biotransformation and pharmacokinetics of ethylmorphine after a single oral dose.

Biotransformation and pharmacokinetics of ethylmorphine after a single oral dose.

Influence of menstrual cycle on cytochrome P450 2A6 activity and cardiovascular effects of nicotine*

The Menstrual Cycle and Drug Metabolism

Contact Info

Product

Resources

About