Variability in metabolism of imipramine and desipramine using urinary excretion data.

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Ramey K, Ma JD, Best BM, Atayee RS, Morello CM

Variability in metabolism of imipramine and desipramine using urinary excretion data.

J Anal Toxicol. 2014 Jul-Aug;38(6):368-74. doi: 10.1093/jat/bku034. Epub 2014 Apr 29.

PubMed ID

24782142 [ View in PubMed

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Abstract

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.

DrugBank Data that Cites this Article

Drug Enzymes

Drug	Enzyme	Kind	Organism	Pharmacological Action	Actions
Desipramine	Cytochrome P450 1A2	Protein	Humans	Unknown	Product of	Details
Desipramine	Cytochrome P450 3A4	Protein	Humans	Unknown	Inhibitor	Details
Imipramine	Cytochrome P450 3A4	Protein	Humans	Unknown	Substrate	Details