norfentanyl and Chronic-Disease

A study of the urinary concentration of fentanyl (F) and its major metabolite norfentanyl (NF) in chronic pain patients treated with the Duragesic continuous release transdermal patches is presented. These patches are available in 10, 20, 30, and 40 cm(2) sizes releasing 25, 50, 75, and 100 microg/h F, respectively. F is rapidly and extensively metabolized, with NF as the major metabolite. Five hundred-forty six random urine specimens were collected from chronic pain patients wearing 25, 50, 75, or 100 ug F transdermal patches. Urine specimens were collected from hours after application to several days later after continuous F release. Each specimen was analyzed for F, NF, creatinine, and pH. Additionally, each was screened by enzyme immunoassay for the following: amphetamines, barbiturates, benzodiazepines, cocaine metabolite, methadone, phencyclidine, d-propoxyphene, opiates, and marijuana metabolites. All positive screening results were confirmed by gas chromatography-mass spectrometry (GC-MS). F and NF were isolated from urine by solid-phase extraction then identified and quantified by GC-MS in SIM mode. The LODs and LOQs for F and NF were 3 ng/mL, respectively. The results of F and NF analysis of urine form those wearing 25-microg patches (N = 142) was mean F, 47 ng/mL with a range of 0 to 983 ng/mL, and 97% of the specimens contained < 200 ng/mL and mean NF, 175 ng/mL with a range of 0-980 ng/mL, while 95% of the specimens contained < 400 ng/mL. The results of F and NF analysis of urine form those wearing 50 microg patches (N = 184) was: mean F, 74 ng/mL with a range of 0 to 589 ng/mL, and 92% of the specimens contained < 200 ng/mL and mean NF, 257 ng/mL with a range of 0-2200 ng/mL, and 98% of the specimens contained < 1000 ng/mL. The results of F and NF analysis of urine form those wearing 75 microg patches (N = 85) was mean F, 107 ng/mL with a range of 0 to 1280 ng/mL, and 98% of the specimens contained < 400 ng/mL and mean NF, 328 ng/mL with a range of 0-5630 ng/mL, and 99% of the specimens contained < 1000 ng/mL. The results of F and NF analysis of urine form those wearing 100 ug patches (N = 135) was mean F, 100 ng/mL with a range of 0 to 1080 ng/mL, while 96% of the specimens contained < 400 ng/mL and mean NF, 373 ng/mL with a range of 0-5730 ng/mL, and 95% of the specimens contained < 1000 ng/mL. The incidence of other drugs detected as a percentage the specimens was opiates, 48%, benzodiazepines, 43%; barbiturates, 3%; methadone, 4%; mariju

Topics: Administration, Cutaneous; Analgesics, Opioid; Chronic Disease; Delayed-Action Preparations; Fentanyl; Gas Chromatography-Mass Spectrometry; Half-Life; Humans; Immunoenzyme Techniques; Pain

Delivery rates and plasma concentrations vary among patients treated with fentanyl patches. Absorption and urinary excretion characteristics of fentanyl were studied in patients undergoing palliative care. Almost 500 patches were analyzed for residual fentanyl content. Fentanyl and norfentanyl levels were determined in the urine of 50 patients. General and mixed effects linear regression models were established for the relationship between fentanyl dose rate and urinary excretion and to incorporate influencing factors. For different patch nominal dose strengths, wide but comparable variability in estimated dose rate and delivery efficiency was observed (coefficients of variation of 15% to 17%). Fentanyl delivery efficiency was 8.5% higher for patches of 25 microg/h as compared to 75 microg/h and, accordingly, 7.5% for patch application on the arm as compared to the leg. Urinary fentanyl and norfentanyl concentrations varied considerably. The general linear model revealed a positive effect of the calculated transdermal dose rate on urinary fentanyl levels, explaining 34% of the variability (P < .0001). In addition, gender (P = .04) and type of cancer pathology (P = .03) exerted significant effects on the linear model, explaining 40% and 64% of the variability, respectively. Delivery efficiency of fentanyl patches can vary substantially, possibly leading to either underdosing or overdosing.

Topics: Administration, Cutaneous; Adult; Aged; Aged, 80 and over; Analgesics, Opioid; Chronic Disease; Dose-Response Relationship, Drug; Drug Carriers; Female; Fentanyl; Humans; Male; Middle Aged; Neoplasms; Pain; Palliative Care; Skin Absorption