RESUMEN
Hydrocodone combined with acetaminophen is commonly used for moderate pain. Hydrocodone is metabolized by cytochrome P450 (CYP) 2D6 into hydromorphone and by CYP3A4 into norhydrocodone. This was a retrospective study evaluating hydrocodone, hydromorphone and norhydrocodone distributions in urine. Urine specimens (n = 76,924) were obtained from patients on chronic opioid therapy during their first or single visit and were analyzed by liquid chromatography-tandem mass spectrometry (LC-MS-MS). The patients were at least 16 years of age and had documented hydrocodone use via a medication list. There were 48,710 specimens that were positive for all three analytes. Mean hydrocodone, hydromorphone and norhydrocodone mole fractions (95% confidence interval) were 0.39 (0.38-0.39), 0.12 (0.11-0.12) and 0.49 (0.48-0.49), respectively. Hydromorphone fractions were lower in women compared with men (0.11 versus 0.13; P < 0.0001). Hydrocodone mole fractions were higher in the 65-year and older age group compared with the 16- to 39-year age group (0.4 versus 0.36; P ≤ 0.005). Concurrent use of a CYP2D6 and/or CYP3A4 inhibitor altered hydromorphone and norhydrocodone mole fractions, compared with the control group. Patient factors affect hydrocodone and metabolite mole fractions and suggest increased awareness of their contribution when attempting to interpret urine drug testing results.
Asunto(s)
Analgésicos Opioides/metabolismo , Analgésicos Opioides/orina , Hidrocodona/metabolismo , Hidrocodona/orina , Dolor/tratamiento farmacológico , Adolescente , Adulto , Factores de Edad , Anciano , Analgésicos Opioides/administración & dosificación , Analgésicos Opioides/uso terapéutico , Cromatografía Liquida , Inhibidores del Citocromo P-450 CYP2D6/administración & dosificación , Inhibidores del Citocromo P-450 CYP2D6/uso terapéutico , Inhibidores del Citocromo P-450 CYP3A/administración & dosificación , Inhibidores del Citocromo P-450 CYP3A/uso terapéutico , Interacciones Farmacológicas , Femenino , Humanos , Hidrocodona/administración & dosificación , Hidrocodona/uso terapéutico , Concentración de Iones de Hidrógeno , Masculino , Persona de Mediana Edad , Dolor/orina , Estudios Retrospectivos , Factores Sexuales , Espectrometría de Masas en Tándem , Distribución Tisular , Orina/química , Adulto JovenRESUMEN
OBJECTIVE: To determine the relationship between urine drug testing (UDT) frequency and patient adherence for prescribed buprenorphine, carisoprodol, fentanyl, hydrocodone, methadone, morphine, and oxycodone. SETTING: Patients with pain routinely seen by private practitioners. DESIGN: A retrospective analysis was conducted on urinary excretion data analyzed by Millennium Laboratories between March 2008 and May 2011. PATIENT PARTICIPANTS: Patients in the United States with chronic pain who underwent routine UDT to confirm adherence for prescribed medications. INTERVENTIONS: Adherence for the urine drug test was defined as the presence of parent drug and/or metabolite(s) greater than or equal to the lower limit of quantitation. The percent of adherence for prescribed medications was compared to the average percent of the same in subjects with five or more visits. MAIN OUTCOMES: Correlation analyses were used to determine the relationship between adherence for prescribed medications and number of visits. RESULTS: There were 255,168 specimens submitted for testing from 166,755 individuals. When monitoring with more frequent visits (≥5 visits) adherence was higher by 1 percent for buprenorphine (89 percent vs 88 percent); 8 percent for carisoprodol (77 percent vs 69 percent); 5 percent for fentanyl (95 percent vs 90 percent); 7 percent for hydrocodone (83 percent vs 76 percent); 3 percent for methadone (96 percent vs 93 percent); 5 percent for morphine (92 percent vs 87 percent); and 8 percent for oxycodone (90 percent vs 82 percent). CONCLUSIONS: Adherence for prescribed medications is higher with frequent urine monitoring. UDT can be used as tool that may help improve this in patients with chronic pain.
Asunto(s)
Analgésicos Opioides/uso terapéutico , Dolor Crónico/tratamiento farmacológico , Cumplimiento de la Medicación , Analgésicos Opioides/orina , Buprenorfina/uso terapéutico , Buprenorfina/orina , Dolor Crónico/orina , Fentanilo/uso terapéutico , Fentanilo/orina , Humanos , Hidrocodona/uso terapéutico , Hidrocodona/orina , Metadona/uso terapéutico , Metadona/orina , Morfina/uso terapéutico , Morfina/orina , Oxicodona/uso terapéutico , Oxicodona/orinaRESUMEN
Hydrocodone in combination with acetaminophen is commonly used to control moderate pain and is metabolized by cytochrome P4502D6 to form the active metabolite, hydromorphone. The purpose of this study was to determine the metabolic relationship and variability between hydrocodone and its conversion to hydromorphone using urinary excretion data from chronic pain patients. Liquid chromatography-tandem mass spectrometry was used to quantitate hydrocodone and hydromorphone concentrations in urine specimens. The first visits of 25,200 subjects who took hydrocodone and not hydromorphone and had measurable concentrations were included in this study. The geometric mean (95% confidence index) of hydrocodone and hydromorphone urine concentrations were 1.39 (1.37-1.41) mg per gram of creatinine and 0.224 (0.221-0.227) mg per gram of creatinine, respectively. The log of creatinine-corrected hydromorphone versus the log of creatinine-corrected hydrocodone showed a positive relationship (R(2) = 0.20), with 60-fold variability between subjects. The plot of the log of the metabolic ratio ([hydromorphone] divided by [hydrocodone]) versus the log of creatinine-corrected hydrocodone had a coefficient of determination of R(2) = 0.42, with 125-fold variability between subjects. Ultra-rapid metabolizers represented 0.6% of the population, whereas 4% were poor metabolizers. Within-subject variability for the excretion of hydrocodone in urine was 23-fold, whereas between-subject variability was 134-fold. Hydrocodone and hydromorphone urine concentrations showed great variability within and between subjects.