Variability in metabolism of imipramine and desipramine using urinary excretion data.
Variability in imipramine and desipramine metabolism was evaluated using urinary excretion data from patients with pain. Liquid chromatography-tandem mass spectrometry was used to quantitate concentrations in urine specimens. Interpatient population contained 600 unique imipramine specimens, whereas intrapatient population had 137 patients with two or more specimens. Normal concentration ranges of imipramine, desipramine and the desipramine/imipramine metabolic ratio (MR) were established, and various factors were tested for MR impact. Geometric mean of imipramine urine concentration was 0.46 mg/g of creatinine, and desipramine was 0.67 mg/g of creatinine. Gender, concomitant known CYP2C19 inhibitor use and urine pH did not affect MR. However, proton-pump inhibitor (PPI) users had a significantly lower mean MR than those without a listed PPI. Early age group (18-36 years) had a significantly higher mean MR than middle (37-66 years) and late (67-90 years) age groups. Approximately one-third were positive for one or more of hydrocodone, oxycodone, hydromorphone or oxymorphone. Patients with no opioids reported in the medication list had a significantly lower geometric mean MR than those with prescribed opioids (1.03 vs. 1.54, P = 0.004). Patients with only one prescribed opioid had a lower MR than those with two or more prescribed opioids. Patients with younger age, prescribed opioids and no listed PPI were more likely to have a higher geometric mean urinary desipramine/imipramine MR.
Skaggs School of Pharmacy and Pharmaceutical Sciences, University of California San Diego (UCSD), Pharmaceutical Sciences Building (PSB), Dean's Suite, Room 1121, 9500 Gilman Drive, MC 0657, La Jolla, CA 92093-0657, USA.
Kelley
K
Ramey
Skaggs School of Pharmacy and Pharmaceutical Sciences, University of California San Diego (UCSD), Pharmaceutical Sciences Building (PSB), Dean's Suite, Room 1121, 9500 Gilman Drive, MC 0657, La Jolla, CA 92093-0657, USA Doris A. Howell Palliative Care Service, San Diego, CA, USA.
Joseph D
JD
Ma
Skaggs School of Pharmacy and Pharmaceutical Sciences, University of California San Diego (UCSD), Pharmaceutical Sciences Building (PSB), Dean's Suite, Room 1121, 9500 Gilman Drive, MC 0657, La Jolla, CA 92093-0657, USA UCSD Department of Pediatrics, Rady Children's Hospital, San Diego, CA, USA.
Brookie M
BM
Best
Skaggs School of Pharmacy and Pharmaceutical Sciences, University of California San Diego (UCSD), Pharmaceutical Sciences Building (PSB), Dean's Suite, Room 1121, 9500 Gilman Drive, MC 0657, La Jolla, CA 92093-0657, USA Doris A. Howell Palliative Care Service, San Diego, CA, USA.
Rabia S
RS
Atayee
Skaggs School of Pharmacy and Pharmaceutical Sciences, University of California San Diego (UCSD), Pharmaceutical Sciences Building (PSB), Dean's Suite, Room 1121, 9500 Gilman Drive, MC 0657, La Jolla, CA 92093-0657, USA Diabetes Intense Medical Management Clinic, Veterans Affairs San Diego Healthcare System, La Jolla, CA, USA candismorello@ucsd.edu.
Candis M
CM
Morello
D000293:Adolescent; D000328:Adult; D000367:Age Factors; D000368:Aged; D000701:Analgesics, Opioid / Q000493:pharmacokinetics; D000929:Antidepressive Agents, Tricyclic / Q000378:metabolism / Q000652:urine; D002853:Chromatography, Liquid; D003404:Creatinine / Q000652:urine; D003891:Desipramine / Q000378:metabolism / Q000652:urine; D004347:Drug Interactions; D005260:Female; D006801:Humans; D006863:Hydrogen-Ion Concentration; D007099:Imipramine / Q000378:metabolism / Q000652:urine; D016014:Linear Models; D008297:Male; D008657:Metabolic Clearance Rate; D008875:Middle Aged; D009437:Neuralgia / Q000188:drug therapy / Q000652:urine; D054328:Proton Pump Inhibitors / Q000493:pharmacokinetics; D012189:Retrospective Studies; D012737:Sex Factors; D053719:Tandem Mass Spectrometry; D014556:Urine / Q000737:chemistry; D055815:Young Adult
D000701:Analgesics, Opioid; D000929:Antidepressive Agents, Tricyclic; D054328:Proton Pump Inhibitors; D003404:Creatinine; D007099:Imipramine; D003891:Desipramine