RESUMEN
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
This retrospective data analysis explored the relationship between codeine and its metabolites morphine, hydrocodone and hydromorphone. The objectives were: (i) to determine urine concentrations and mole fractions of codeine and metabolites and (ii) to examine the effect of cytochrome P450 (CYP) 2D6 inhibition on metabolite mole fractions. De-identified urine specimens were collected between September 2010 and July 2011 and analyzed using LC-MS-MS to determine codeine, morphine, hydrocodone and hydromorphone concentrations. Geometric mean urine concentrations were 0.833, 0.085 and 0.055 for morphine, hydrocodone and hydromorphone, respectively. Mole fractions were 0.23, 0.025 and 0.014 for morphine, hydrocodone and hydromorphone, respectively. The fraction of excreted codeine in the urine increased (slope = 0.06 ± .01, R² = 0.02) with total moles. As the total amount of codeine and metabolites increased, the fraction of codeine increased, while the fraction of active metabolites decreased. CYP2D6 inhibition with paroxetine, fluoxetine, bupropion and methadone significantly decreased the fraction of morphine excreted. The prevalence of codeine metabolism to morphine was considerably higher than codeine to hydrocodone. The urine concentration of codeine excreted was the greatest, followed by morphine and hydrocodone. Subjects should be monitored during concomitant use of codeine and CYP2D6 inhibitors as this affects the amount of morphine metabolite formation.
Asunto(s)
Analgésicos Opioides/uso terapéutico , Analgésicos Opioides/orina , Codeína/uso terapéutico , Codeína/orina , Monitoreo de Drogas/métodos , Dolor/tratamiento farmacológico , Analgésicos Opioides/efectos adversos , Analgésicos Opioides/farmacocinética , Biotransformación , Codeína/efectos adversos , Codeína/farmacocinética , Citocromo P-450 CYP2D6/metabolismo , Inhibidores del Citocromo P-450 CYP2D6 , Interacciones Farmacológicas , Inhibidores Enzimáticos/uso terapéutico , Humanos , Hidrocodona/orina , Hidromorfona/orina , Dolor/diagnóstico , Dolor/orina , Estudios Retrospectivos , Medición de Riesgo , Factores de Riesgo , UrinálisisRESUMEN
The object of this study was to evaluate the metabolism of oxycodone to oxymorphone in a pain patient population using a quantitative liquid chromatography-tandem mass spectrometry analysis of 32,656 urine specimens obtained from pain patients between March 2008 and Feb 2010. The observed excretion was modeled using logarithmic transformation and approximated a Gaussian distribution. Oxycodone excretion into urine had a geometric mean of 1.93 mg/g of creatinine and oxymorphone had a value of 0.41 mg/g of creatinine. Increasing concentrations of oxycodone correlated with a smaller proportion of oxymorphone excretion suggesting saturation of oxycodone metabolism. Urine samples containing oxycodone without oxymorphone allowed an estimation of the proportion of poor metabolizers (2.4 ± 2.1%) in the population. A similar analysis of samples containing oxymorphone without oxycodone gave an estimate of the proportion of ultra-rapid metabolizers (1.8 ± 1.1%) in the population. Samples with concentrations of oxycodone above 10 mg/g of creatinine showed a sub-population of subjects with metabolic ratios roughly 100-fold less than the linear predictive model in this study. This study describes typical ranges for oxycodone and oxymorphone in urine, and showed that it is possible to identify fast or slow metabolizers who may be at risk for adverse events.