Tretinoin (tretinoin)

Tretinoin, a retinoid, is an antineoplastic agent.

Tretinoin is a retinoid that induces cytodifferentiation and decreased proliferation of acute promyelocytic leukemia (APL) cells in culture and in vivo. The precise mechanism(s) of action of tretinoin has not been fully elucidated. The PML/RAR-alpha fusion protein resulting from the 15;17 chromosomal translocation appears to block myeloid differentiation at the promyelocyte stage, possibly by complexing and inactivating wild-type PML or by inhibiting the normal retinoic acid signaling pathway.

In patients with APL who achieve a complete remission with tretinoin therapy, the drug causes an initial maturation of the primitive promyelocytes derived from the cellular leukemic clone followed by a repopulation of the bone marrow and peripheral blood by normal, polyclonal hematopoietic cells. Observations supporting cellular differentiation effects as a mechanism of tretinoin include the absence of bone marrow hypoplasia during induction, the appearance of immunophenotypically unique ''intermediate cells'' expressing both mature and immature cell surface antigens, and the presence of both Auer rods and the 15;17 translocation in morphologically mature granulocytes until a late stage of induction. The mechanism by which the population of malignant cells is eliminated is not fully understood but appears to involve apoptosis (programmed cell death).

Following induction therapy, the PML/RAR-alpha fusion protein can be detected in the majority of patients, suggesting that tretinoin alone does not eradicate the leukemic clone.

Following oral administration of tretinoin, the time to reach peak concentrations was 1 to 2 hours. The absolute bioavailability was approximately 50%. The effect of food on absorption has not been evaluated; however, retinoid absorption is generally enhanced with food.

Protein binding is >95%, primarily to albumin. The terminal elimination half-life of tretinoin following initial dosing in patients with APL is 0.5 to 2 hours. Tretinoin is metabolized in the liver by cytochrome P-450 (CYP) isoenzymesCYP3A4, 2C8, and 2E and undergoes glucuronidation by UGT2B7; evidence exists that tretinoin induces its own metabolism.

Two ofits metabolites, 4-oxo retinoic acid and 4-oxo trans retinoic acid glucuronide, have 33% of the pharmacological activity of the parent compound. The drug is excreted in the feces (31% within 6 days)andurine (63% within 72 hours). Theeffect of age, sex, race, renal impairment, and hepatic impairment on the pharmacokinetics of tretinoin is unknown.

USES: Tretinoin is used to treat a certain type of cancer (APL-acute promyelocytic leukemia). People with APL have too many abnormal blood cells which may cause symptoms such as infections or tiredness. This medication works by stopping the growth of abnormal blood cells and may help decrease symptoms of APL.

Tretinoin belongs to a class of drugs known as retinoids, which are related to vitamin A.

Generic name: tretinoin
Pronunciation: (TRET-i-noyn)

The following indications are listed for Tretinoin:

• Acute Promyelocytic Leukemia

Also known as: Promyelocytic Leukemia.

No ICD codes are available for this drug.