About this pathway
Background
Pitavastatin is an HMG-CoA reductase inhibitor (statin) used for the lower cholesterol in patients with hyperlipidemia. Similar to other statins, pitavastatin inhibits endogenous cholesterol production by competitive inhibition of 3-hydroxy-3-methylglutaryl coenzyme A reductase (HMGCR), the enzyme that catalyzes conversion of HMG-CoA to mevalonate depicted in the Statin Pathway, Pharmacodynamics.
Guideline regarding the use of pharmacogenomic information in dosing for lovastatin was published by the Clinical Pharmacogenetic Implementation Consortium (CPIC). CPIC recommends reduced pitavastatin starting dose for patients with SLCO1B1 rs4149056 (521T>C) CC or TC genotype, or patients with SLCO1B1 decreased function, or poor function phenotype.
Metabolism
The primary route of pitavastatin metabolism is glucuronidation by UDP-glucuronosyltransferase enzymes UGT1A1, 1A3 and 2B6 in the liver [Article:12519692], with subsequent formation of pitavastatin lactone. Only a very small percentage of metabolism is via the cytochrome P450 system. It is marginally metabolized by CYP2C9 [Article:15118259].
Transport
Pitavastatin is a substrate of organic anion transporters SLCO1B1 and SLCO1B3 [Article:31699807] and efflux transporters ABCB1, ABCC3 and ABCG2 [Articles:34045219, 34162690].
Genetic variations in the SLCO1B1 gene have been linked to increased exposure of pitavastatin. Carriers of the rs4149056 (521T>C) C allele had increased AUC and decreased clearance of pitavastatin [Articles:16198653, 17460607, 18408565, 30528195, 23556337, 23007012]. This variant had no significant effect on lipid-lowering effect of pitavastatin [Article:20140004].
Reactions & interactions (17)
-
Biochemical Reaction
pitavastatin lactone → 8-hydroxy pitavastatin
-
Biochemical Reaction
pitavastatin → 5-oxo pitavastatin
-
Biochemical Reaction
pitavastatin → 8-hydroxy pitavastatin
-
Biochemical Reaction
pitavastatin acyl glucuronide → pitavastatin lactone
-
Biochemical Reaction
pitavastatin → pitavastatin acyl glucuronide
-
Catalysis
ABCG2 → Transport
-
Catalysis
ABCB1 → Transport
-
Catalysis
ABCC3 → Transport
-
Catalysis
CYP2D6 → Biochemical Reaction
-
Catalysis
CYP3A4 → Biochemical Reaction
-
Catalysis
SLCO1B3 → Transport
-
Catalysis
SLCO1B1 → Transport
-
Catalysis
UGT1A3 → Biochemical Reaction
-
Catalysis
UGT2B7 → Biochemical Reaction
-
Catalysis
UGT1A1 → Biochemical Reaction
-
Transport
pitavastatin → pitavastatin
-
Transport
pitavastatin → pitavastatin
Edit history (3)
- 2021-12-15 Create
- 2022-02-20 Update Linked related statin pathways.
- 2025-03-24 Update fixed typo