Pathways

PharmGKB pathways are evidence-based diagrams depicting the pharmacokinetics (PK) and/or pharmacodynamics (PD) of a drug with relevant (or potential) pharmacogenetic (PGx) associations. Drugs featured in PharmGKB pathways are chosen through extensive review of a variety of sources, including, but not limited to, the U.S. Food and Drug Administration (FDA) biomarker list and Clinical Pharmacogenetics Implementation Consortium (CPIC) nominations.

PharmGKB pathways are accompanied by a written summary of the PK and/or PD pathway, as well as other important PGx related information. Interactions within each pathway are supported by manually curated evidence from published literature and specific information for each arrow in the pathway is found on the “Components” tab. Information contained within each pathway is available for download in TSV, BioPAX and GPML formats. The pathway graphic is available for download in PDF file format. PharmGKB pathways are often published in the journal Pharmacogenetics and Genomics.

CategoryCount
Anti-infective agents 9
Anticancer agents 34
Cardiovascular and hematology agents 17
Endocrine and Metabolic Disease agents 6
Gastrointestinal agents 2
Musculoskeletal agents 6
Neurological agents 19
Pain, anti-inflammatory and immunomodulating agents 12
Physiological mechanisms 5
Respiratory agents 5
NameThumbnailCategoryPublished
Schematic representation of abacavir metabolism and mechanism of action. The potential mechanism of an abacavir hypersensitivity reaction is also shown.
Anti-infective agents
PMID:24625462
Model, non-tissue-specific cell displaying genes which may be involved in the ACE inhibitor pathway
Cardiovascular and hematology agents
Stylized diagram showing acetaminophen metabolism and transport in the liver.
Pain, anti-inflammatory and immunomodulating agents
PMID:26049587
Stylized diagram showing acetaminophen metabolism at higher acetaminophen doses (toxic doses) in the liver
Pain, anti-inflammatory and immunomodulating agents
PMID:26049587
Genes involved in the pharmacodynamics of the drugs that act on the renin-angiotensin-aldosterone system.
Cardiovascular and hematology agents
Anti-infective agents
Nateglinide metabolism and transport in liver cell
Endocrine and Metabolic Disease agents
Representation of anti-diabetic drugs repaglinide, nateglinide and sulfonylurea effects on insulin secretion in pancreatic cells.
Endocrine and Metabolic Disease agents
Repaglinide metabolism and transport in a liver cell.
Endocrine and Metabolic Disease agents
Pharmacodynamic pathway of antiarrhythmic drugs in a stylized cardiac myocyte.
Cardiovascular and hematology agents
Model non-tissue specific cancer cell displaying candidate genes which may be involved in the pharmacodynamics of antimetabolite drugs acting on the folate cycle.
Anticancer agents
Summary of pathways of estrogens and antiestrogens.
Anticancer agents
Diagrammatic representation of the synthesis of estrogen in post-menopausal women and its blockade by aromatase inhibitors.
Anticancer agents
PMID:19512956
Anti-infective agents
Drug-specific representation of the candidate genes involved in transport, metabolism and clearance.
Cardiovascular and hematology agents
Neurological agents
Neurological agents
Simplified pharmacodynamic pathway of drug action on beta 2 adrenergic receptor in a stylized airway cell.
Cardiovascular and hematology agents
Respiratory agents
Representation of genes involved in bisphosphonates' effects in osteoclasts.
Musculoskeletal agents
PMID:20023594
Anticancer agents
Stylized liver cell showing candidate genes involved in the metabolism of caffeine.
Pain, anti-inflammatory and immunomodulating agents
Neurological agents
PMID:22293536
Stylized liver cell depicting candidate genes involved in the pharmacokinetics of carbamazepine.
Neurological agents
PMID:21738081
Stylized cell depicting the mechanism of action of celecoxib and candidate genes interacting with celecoxib and involved in the regulation of cell cycle, apoptosis and angiogenesis by celecoxib.
Pain, anti-inflammatory and immunomodulating agents
Musculoskeletal agents
PMID:22336956
Pain, anti-inflammatory and immunomodulating agents
Musculoskeletal agents
PMID:22336956
Pharmacokinetics of the selective serotonin reuptake inhibitor citalopram.
Neurological agents
PMID:21546862
Schematic representation of clomipramine metabolism in human liver.
Neurological agents
Clopidogrel metabolism.
Cardiovascular and hematology agents
PMID:20440227
Representation of the candidate genes involved in metabolism of codeine and morphine.
Pain, anti-inflammatory and immunomodulating agents
PMID:19512957
Model non-tissue-specific cancer cell displaying genes which may be involved in the cyclophosphamide pathway.
Anticancer agents
Model human liver cell showing genes involved in the metabolism of cyclophosphamide.
Anticancer agents
Diagrammatic representation of candidate genes involved in the pharmacodynamics of diuretics in a stylized kidney cell.
Cardiovascular and hematology agents
PMID:23788015
Stylized liver cell showing candidate genes involved in the metabolism of the tricyclic doxepin.
Representation of the candidate genes involved in the action of doxorubicin in a stylized cancer cell.
Anticancer agents
PMID:21048526
Representation of the candidate genes involved in adverse effects of doxorubicin in a stylized cardiomyocyte.
Anticancer agents
PMID:21048526
Diagrammatic representation of the transport and metabolism of doxorubicin.
Anticancer agents
PMID:21048526
Schematic representation of efavirenz metabolism and mechanism of action against HIV.
Anti-infective agents
Model non-tissue specific cancer cell displaying genes that may be involved in the treatment using epidermal growth factor receptor specific tyrosine kinase inhibitors or monoclonal antibodies.
Anticancer agents
Model human liver cell showing genes involved in the transportation and metabolism of Erlotinib.
Anticancer agents
Estrogen metabolism in the liver.
Physiological mechanisms
Etoposide cellular disposition and effects.
Anticancer agents
PMID:19512958
Model non-tissue-specific cancer cell displaying genes which may be involved in the pharmacodynamics of the fluoropyrimidines, 5-fluorouracil (5-FU), capecitabine and tegafur.
Anticancer agents
PMID:20601926
Representation of the metabolic pathways for fluoropyrimidines.
Anticancer agents
PMID:20601926
Representation of the candidate genes involved in the metabolism of fluoxetine.
Neurological agents
Drug-specific representation of the candidate genes involved in transport, metabolism and clearance.
Cardiovascular and hematology agents
Representation of the candidate genes involved in the transportation and metabolism of gefitinib.
Anticancer agents
Model non-tissue specific cancer cell displaying genes which may be involved in the gemcitabine pathway.
Anticancer agents
PMID:25162786
Anticancer agents
Simplified diagram of the actions of corticotropin releasing factor(CRH) and related hormones which regulate the release of glcocorticoids via the hypothalamic pituitary adrenal axis.
Physiological mechanisms
Genes involved in mediating glucocorticoid effects at the tissue level in the CNS and in the peripheral tissues including heart, lung, vasculatrue and guts.
Respiratory agents
Model displaying genes which may be involved in the nuclear complex formed that regulates transcription in response to glucocorticoids.
Respiratory agents
Stylized cell depicting the mechanism of action of ibuprofen (IBU).
Pain, anti-inflammatory and immunomodulating agents
PMID:25502615
Stylized diagram of metabolism and transport of ibuprofen in the liver and kidney.
Pain, anti-inflammatory and immunomodulating agents
PMID:25502615
Model non-tissue specific cancer cell displaying genes which may be involved in the ifosfamide pathway.
Anticancer agents
PMID:24401834
Model human liver cell showing genes involved in the metabolism of ifosfamide.
Anticancer agents
PMID:24401834
Anticancer agents
Representation of the candidate genes involved in the metabolism of the tricyclic antidepressants imipramine and desipramine.
Neurological agents
Model non-tissue specific cancer cell displaying genes which may be involved in the irinotecan pathway.
Anticancer agents
Model human liver cell showing blood, bile and intestinal compartments, indicating tissue specific involvement of genes in the irinotecan pathway.
Anticancer agents
Representation of candidate genes involved in the metabolism of lamivudine and its mechanism of antiviral action.
Anti-infective agents
Respiratory agents
Representation of the candidate genes involved in the metabolism of losartan.
Cardiovascular and hematology agents
Endocrine and Metabolic Disease agents
PMID:22722338
Endocrine and Metabolic Disease agents
PMID:22722338
Representation of transport and exchange of methotrexate in the brain.
Anticancer agents
PMID:21317831
Methotrexate cellular disposition and effects.
Anticancer agents
PMID:21317831
Diagramatic representation of uptake, transport and elimination of methotrexate.
Anticancer agents
Musculoskeletal agents
PMID:21317831
A stylized diagram showing the mechanisms that can cause methemoglobin production in erythrocytes and the control mechanisms to prevent methemoglobinemia, including methylene blue treatment which requires NADPH from the Pentose Phosphate Pathway.
Cardiovascular and hematology agents
PMID:23913015
Schematic representation of mycophenolic acid metabolism.
Pain, anti-inflammatory and immunomodulating agents
PMID:24220207
Representation of candidate genes involved in biotransformation of nevirapine and its mechanism of action in an infected liver cell.
Anti-infective agents
Representation of genes involved in nicotine effects in chromaffin cells.
Neurological agents
Representation of genes involved in nicotine effects in dopaminergic neurons.
Neurological agents
Summary of nicotine metabolism in human liver cell.
Neurological agents
A simplified diagram to show several of the regulatory mechanisms that prevent oxidative stress in red blood cells, many of which require NADPH from the Pentose Phosphate Pathway.
Physiological mechanisms
PMID:23913015
Genes involved in the metabolism of paroxetine and in the mechanism of action.
Neurological agents
Proposed mechanism of action of peginterferon alpha (PEG-IFN-α) based therapies for chronic Hepatitis C.
Anti-infective agents
PMID:26111151
A simplified diagram to show the role of G6PD in generating NADPH in red blood cells - this can then be utilized in the Oxidative Stress Regulatory and Methylene Blue Pathways.
Physiological mechanisms
PMID:23913015
Genes involved in the metabolism of phenytoin in the human liver cell.
Neurological agents
PMID:22569204
Effects of antiplatelet drugs on platelet aggregation pathway.
Cardiovascular and hematology agents
PMID:20938371
Representation of the candidate genes involved in the metabolism of platinum containing drugs.
Anticancer agents
PMID:19525887
Drug-specific representation of the candidate genes involved in transport, metabolism and clearance.
Cardiovascular and hematology agents
Genes involved in the proton pump activation and trafficking.
Gastrointestinal agents
Omeprazole metabolism in the liver.
Gastrointestinal agents
Rosiglitazone is transported from hepatic sinusoids into hepatocytes -- a process mediated by the organic anion transporting polypeptide, where is is metabolized by cytochrome p450 2C8 and 2C9.
Endocrine and Metabolic Disease agents
Drug-specific representation of the candidate genes involved in transport, metabolism and clearance.
Cardiovascular and hematology agents
Genes involved in serotonin synthesis, release, reuptake, and in mediation of the antidepressant effect of selective serotonin reuptake inhibitors (SSRI) in human brain.
Neurological agents
PMID:19741567
Mechanism of action of sorafenib
Anticancer agents
Anticancer agents
Representation of the superset of all genes involved in the transport, metabolism and clearance of statin class drugs.
Cardiovascular and hematology agents
Genes involved in mediating statin effects on hepatic cholesterol metabolism and consequent effects on plasma lipoprotein transport.
Cardiovascular and hematology agents
Simplified diagram of a sympathetic neuroeffector junction displaying genes which may be involved.
Neurological agents
Simplified diagram of a sympathetic neuronal junction displaying genes involved in neurotransmitter biosynthesis in response to neuronal stimulation.
Neurological agents
Stylized cell depicting the mechanism of action of tacrolimus and cyclosporine, as well as the candidate genes believed to interact with the two drugs.
Pain, anti-inflammatory and immunomodulating agents
PMID:23922006
Schematic representation of tacrolimus and cyclosporine metabolism
Pain, anti-inflammatory and immunomodulating agents
PMID:23922006
Tamoxifen metabolism in the liver.
Anticancer agents
PMID:23962908
Representation of the genes involved in the metabolism and transport of paclitaxel and docetaxel, and the downstream effects of the drugs.
Anticancer agents
PMID:21151855
Representation of candidate genes involved in renal elimination of tenofovir and adefovir and their mechanism of action in an infected kidney cell
Anti-infective agents
Schematic representation of theophylline metabolism in human liver.
Respiratory agents
Anticancer agents
Physiological mechanisms
PMID:19952870
Pain, anti-inflammatory and immunomodulating agents
PMID:24849324
A stylized diagram showing the drugs that act to prevent uric acid formation or enhance its excretion, and adverse reactions associated with these drugs.
Musculoskeletal agents
PMID:24915143
A stylized diagram of a renal proximal tubule cell to show the role of uricosuric drugs in preventing reabsorption of uric acid in human kidney.
Musculoskeletal agents
PMID:24915143
Graphic representation of the candidate genes involved in valproic acid pharmacodynamics.
Neurological agents
PMID:23407051
Graphic representation of the candidate genes involved in valproic acid pharmacokinetics.
Neurological agents
PMID:23407051
Model endothelial cell displaying genes of the VEGF signalling pathway and the sites at which bevacizumab, sorafenib, sunitinib, brivanib and cilengitide are known to act.
Anticancer agents
PMID:20124951
Anticancer agents
Stylized cells depicting the metabolism and mechanism of action of venlafaxine.
Neurological agents
PMID:24128936
Representation of the genes involved in the metabolism, transport, and downstream effects of the vinca alkaloid vincristine.
Anticancer agents
Simplified diagram of the target of warfarin action and downstream genes and effects.
Cardiovascular and hematology agents
Representation of the candidate genes involved in transport, metabolism and clearance of warfarin.
Cardiovascular and hematology agents
Representation of candidate genes involved in the metabolism of zidovudine and its mechanism of antiviral action.
Anti-infective agents
PMID:22960662