Peak plasma concentrations occur around 2–6 hours (with an average of 4.7 hours) after taking clomipramine orally and are in the range of 56–154 ng/mL (178–489 nmol/L). Steady-state concentrations of clomipramine are around 134–532 ng/mL (426–1,690 nmol/L), with an average of 218 ng/mL (692 nmol/L), and are reached after 7 to 14 days of repeated dosing. Steady-state concentrations of the active metabolite, desmethylclomipramine, are around 230–550 ng/mL (730–1,750 nmol/L). The volume of distribution (Vd) of clomipramine is approximately 17 L/kg. It binds approximately 97–98% to plasma proteins, primarily to albumin. Clomipramine is metabolized in the liver mainly by CYP2D6. It has a terminal half-life of 32 hours, and its N-desmethyl metabolite, desmethylclomipramine, has a terminal half-life of approximately 69 hours. Clomipramine is mostly excreted in urine (60%) and feces (32%). Chemistry
Clomipramine is a tricyclic compound, specifically a dibenzazepine, and possesses three rings fused together with a side chain attached in its chemical structure. Other dibenzazepine TCAs include imipramine, desipramine, and trimipramine. Clomipramine is a derivative of imipramine with a chlorine atom added to one of its rings and is also known as 3-chloroimipramine. It is a tertiary amine TCA, with its side chain-demethylated metabolite desmethylclomipramine being a secondary amine. Other tertiary amine TCAs include amitriptyline, imipramine, dosulepin (dothiepin), doxepin, and trimipramine. The chemical name of clomipramine is 3-(3-chloro-10,11-dihydro-5H-dibenzo[b,f]azepin-5-yl)-N,N-dimethylpropan-1-amine and its free base form has a chemical formula of C19H23ClN2 with a molecular weight of 314.857 g/mol. The drug is used commercially almost exclusively as the hydrochloride salt; the free base has been used rarely.
grade 3 or 4 carcinoma): MUC1 (also termed EMA), TP63 (also termed p63; which is detected with the p40 antibody), and various members of the keratin family of proteins. Melanoma: MLANA (i.e. melanoma antigen recognized by T cells 1 protein), S100, and PMEL (a product of the PMEL gene which is detected using an antibody termed HMB-45.) proteinsTwo other tumors that may be confused with UPS have microscopic histopathological and/or other features that help make this distinction. These tumors and features are:
Pleomorphic liposarcoma: At least some tumor cells have features of pleomorphic lipoblasts, i.e. variable shaped immature fat cells. Malignant peripheral nerve sheath tumor: Typically occurs in young children, often develops in a preexisting inoperable plexiform neurofibroma, and often associated with neural tissue. These tumors typically show undifferentiated, pleomorphic cells that are arranged in whorls, parallel bundles, or rosettes (i.e. circular arrangement resembling leaves in a flowering plant) and often contain large areas of necrosis (i.e. dead or dying cells). Treatment and prognosis
The most often used treatment for localized (i.e. no metastases) UPS tumors is complete surgical removal with the object of leaving no tumor cells behind as evidenced by microscopic examinations. Adjuvant therapy combining radiotherapy or/and chemotherapy with surgical resection is employed to reduce the risk of developing recurrent and metastatic disease in cases with high-risk disease (e.g. large tumors, tumors deemed highly aggressive based on their pathology and/or local invasiveness, inoperable tumors, and resections that did not remove all tumor cells).