However, it should be noted that numerous mechanisms have been suggested to explain the observed sex differences and should not be discounted. These include, but are not limited to, higher estrogen concentrations in women, the relationship between analgesic and antianalgesic properties, psychological factors and genetic influences Physiologic factors such as hepatic function, renal function, liver mass and hepatic blood flow are known to decrease with age In the current study, hydrocodone mole fractions were higher in the year and older age group compared with the to year age group.
This seems to suggest an age-related reduction in metabolic capacity of hydrocodone, such as decreased CYP2D6 activity, since the extent of hydromorphone metabolite formation was low. Regardless of which physiologic factor impacted hydrocodone and hydromorphone mole fractions, it is of practical value to closely monitor a patient's response to opioid medication use. In the older adult, cognitive function and functional mobility may be compromised, which place these individuals at a higher fall risk.
Data are limited describing the relationship between the amount excreted of opioid and corresponding urinary pH. Methadone is one example whereby excretion is urinary pH-dependent, while the metabolite EDDP is not dependent on pH A significant difference in the excretion pattern of the parent drug and metabolites based on urinary pH was observed in this study Table II.
The urine specimens used for the analysis had a variable pH range. These results suggest a need to minimize urinary pH variations by several approaches, including, but not limited to, maintaining specimen integrity at the collection site and during laboratory analysis Interindividual variability of hydrocodone pharmacokinetics and pharmacodynamics is due, in part, to CYP2D6- and CYP3A4-mediated drug—drug interactions 5 , Our results are in agreement, as hydromorphone mole fractions during concurrent use of a CYP2D6 inhibitor were lower compared with the control group Table III.
Norhydrocodone mole fractions were also higher and suggest a compensatory metabolic pathway. Hydrocodone mole fractions did not change during concurrent CYP2D6 inhibitor use. This may be due to the contribution of an alternative metabolic pathway i. Our results are in agreement, as norhydrocodone mole fractions during concurrent use of a CYP3A4 inhibitor were lower compared with the control group Table III. A compensatory metabolic pathway would also be anticipated and result in higher hydromorphone mole fractions.
However, this was not observed as there was no statistically significant difference in hydromorphone mole fractions during concurrent CYP3A4 inhibitor use compared with the control group Table III. Rather, hydrocodone mole fractions were higher in the CYP3A4 inhibitor group, which is likely due to parent drug accumulation. We speculate that CYP2D6 inhibitor use plays a more prominent role in contributing to hydrocodone and metabolite mole fraction differences compared with CYP3A4 inhibitor use.
The current study lacked dosing administration of hydrocodone. One study has suggested that peak urine concentrations occur 3—9 h after administration, with detection times of 28, 26 and 40 h for hydrocodone, hydromorphone and norhydrocodone, respectively Another study limitation was the presumption of medication use from physician-reported medication lists.
Attempts to limit this confounding variable included exclusion of specimens with detectable concentrations of morphine and codeine. Additionally, subjects who were taking hydrocodone may have been study exclusions on the basis of unreported use. Rather, CYP genotyping is generally performed on a reactive basis, in an effort to possibly explain a challenging clinical scenario e. Even with medications such as antidepressants and tamoxifen, with known alterations based on CYP2D6 genotype 33 , 34 , formal recommendations are lacking to genotype all patients prior to initiating therapy.
There were 48, specimens that were positive for all the three analytes. Norhydrocodone had the highest mole fraction, followed by hydrocodone and hydromorphone. Women had lower hydrocodone and hydromorphone, but higher norhydrocodone mole fractions.
Hydrocodone mole fractions were higher in the year and older age group compared with the to year age group. However, the extent of hydromorphone metabolite formation was low. Hydrocodone and metabolites are affected by urinary pH variations. The authors acknowledge Amadeo J. Urine specimens were tested and provided by Millennium Laboratories.
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Sign In. Advanced Search. Search Menu. Article Navigation. Close mobile search navigation Article Navigation. Volume Article Contents Abstract. Barakat , Neveen H. Oxford Academic. Rabia S. Brookie M. Joseph D. Cite Cite Neveen H. A Opioids. In Shaw. AACC Press. Washington, D. Stout, P. In Ropero-Miller J. Handbook of Workplace Drug Testing 2nd edition, Chapter Food and Drug Administration, Zohydro Retrieved from FDA. Baselt, R. American Association of Medical Review Officers.
MRO Alert , 8 , Hydromorphone and norhydrocodone are both metabolites of hydrocodone. Dihydrocodeine is also a minor metabolite. Trace amounts of hydrocodone can also be found in the presence of approximately fold higher concentrations of oxycodone or hydromorphone since it can be a pharmaceutical impurity in these medications.
Hydromorphone is metabolized primarily in the liver and is excreted primarily as the glucuronidated conjugate, with small amounts of parent drug and minor amounts of 6-hydroxy reduction metabolites.
Hydromorphone is also a metabolite of hydrocodone; therefore, the presence of hydromorphone could also indicate exposure to hydrocodone. This procedure reports the total urine concentration; this is the sum of the unconjugated and conjugated forms of the parent drug. Other drugs in the opioid class, such as fentanyl, meperidine, methadone, and opiate antagonists such as naloxone, are not detected.
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