What CYP Enzymes Metabolize Teriflunovide?
You’ve probably been wondering: what CYP enzymes metabolize teriflunomide? You’re not alone! Even though many people take antidepressants, there’s not much information on the specific metabolizing enzymes involved in drug metabolism. Here are some realities you may not know. For example, CYP2C19 is a critical player in teriflunomide metabolism.
The enzyme CYP2D6 is one of the essential enzymes for the metabolism of most psychotropic drugs, such as teriflunomide. However, it has recently been implicated in the increased risk of adverse drug events (ADRs) and toxicity in patients. However, not all investigations have analyzed the relationship between CYP2D6 and H. pylori eradication, although it is believed that both enzymes play a significant role in the metabolism of these drugs.
CYP2C19 contributes to the metabolism of a variety of clinically relevant drugs. These include the antiplatelet drug clopidogrel, which reduces the risk of MI and stroke in patients with ACS or atherosclerotic vascular disease. Patients undergoing PCI also benefit from clopidogrel in combination with aspirin to decrease the risk of MI. However, CYP2C19 is required to convert the drug into its active metabolite, and individuals with low activity of this enzyme cannot activate clopidogrel.
The CYP2C19*2 genotype are more likely
Patients carrying the CYP2C19*2 genotype are more likely to be poor or intermediate metabolizers than intermediate or rapid metabolizers. Moreover, a significant proportion of individuals with a CYP2C19*2 loss-of-function genotype are poor metabolizers. A study involving a large cohort of patients will reveal which patient characteristics influence the risk of leflunomide discontinuation.
The study used a Cox proportional hazard model to estimate discontinuation rates by CYP2C19 phenotypes. Those with ultra-rapid CYP2C19 were less likely to discontinue teriflunomide than those with intermediate/poor CYP2C19 metabolize it. In addition, non-Caucasian subjects were excluded from the analysis. The overall effect of the CYP2C19 phenotype on the risk of teriflunomide discontinuation was 0.410 (0.59) after accounting for the current leflunomide dose.
AUBAGIO may cause fetal harm if administered to pregnant women. However, animal studies have not investigated the effect of male-mediated toxicity on fetuses. Hence, men who wish to father a child should use effective contraception and undergo an accelerated elimination procedure. The optimal period for pregnancy is after the plasma teriflunomide concentration is less than 0.02 mg/L.
Acute toxicity caused by teriflunomide
Acute toxicity caused by teriflunomide in pregnant mice was low. However, the drug caused skeletal defects and fetal death. The maternal plasma exposure at a no-effect dose was less than the MRHD in humans. And teriflunomide has the exact mechanism of metabolization, resulting in similar levels in the blood and urine. Therefore, this drug is safe for pregnant women.
However, several other genetic variants in the CYP2C19 enzyme are known to affect a patient’s response to drugs. Although the CYP2C19 enzyme is an essential enzyme for drug metabolism, it isn’t easy to interpret genetic data related to the functional status of CYP2C19. It is important to note that CYP2C19 variants have a relatively small number of functional alleles in the human genome, and the results of such studies should be interpreted with caution.
Teriflunomide is a disease-modifying therapy used to treat multiple sclerosis (MS). Although a cure is not yet available, it has been shown to reduce the risk of relapse, improve MRI lesion activity, and slow disability progression. The American Academy of Neurology recommends teriflunomide for patients with RRMS who have recent relapses or have lesion activity. Clinical decision-making should include safety, tolerability, efficacy, cost, and the potential for adverse effects.
Synthesis inhibitor CYP2C8
The active ingredient in teriflunomide is pyrimidine synthesis inhibitor CYP2C8. It inhibits an enzyme called dihydroorotate dehydrogenase, which is involved in de novo pyrimidine synthesis. Teriflunomide reduces the number of activated lymphocytes in the central nervous system. Its half-life is 18 to 19 days.
Patients with hepatic impairment may have a reduced ability to metabolize teriflunomide. However, patients with mild to moderate hepatic impairment may experience alopecia, paresthesia, or diarrhea. Because teriflunomide inhibits CYP1A2 and CYP2C8, the drug may have a reduced effect on its efficacy.
In the case of people with immunodeficiency, teriflunomide may increase the risk of opportunistic infections. This drug should not be given to patients with severe immunodeficiency, as it may increase their risk of developing opportunistic infections. It can also improve the risk of developing malignancy or lymphoproliferative disorders. It is essential to discuss the risks with your doctor before starting treatment.
Besides affecting CYP2C8 activity
Besides affecting CYP2C8 activity, teriflunomide can inhibit the absorption of abemaciclib. In addition, teriflunomide may reduce the serum concentrations of acenocoumarol. Acyclovir and cholestyramine may also decrease the absorption of teriflunomide.
The primary metabolite of teriflunomide is hydroxylated in humans. CYP2C8 has a range of levels of bilirubin and transaminase. Both drugs have similar ranges of plasma concentrations, although concomitant use of potentially hepatotoxic drugs should be monitored carefully. Patients with hepatic dysfunction should discontinue teriflunomide if these levels increase to 3 times ULN.
Teriflunomide can increase levels of levonorgestrel, a hormone that affects antibody response to live virus vaccines. Therefore, patients should report any symptoms of teriflunomide to their clinician. Furthermore, patients should notify their healthcare professional if they experience serious skin problems, mainly if they develop a rash or have urticaria. Among other serious side effects, teriflunomide can cause severe nausea and diarrhea.
Patients with impaired CYP2C8 activity may experience an increased number of scans without gadolinium-enhancing lesions during treatment with teriflunomide. They also reported fewer relapses and less corticosteroid use. The sedative effect of teriflunomide can cause a relapse. Besides, teriflunomide decreased platelet counts during treatment.
The active drug teriflunomide
The liver enzyme CYP2C9 metabolizes teriflunomide to produce the active drug teriflunomide. When teriflunomide is administered orally, the plasma concentrations were three times the human MRHD. Therefore, it is unlikely to cause a teratogenic effect in human beings. However, it may cause a teratogenic effect in human beings if the doses are higher than the recommended limit.
The gene encoding for CYP2C9 is highly polymorphic, and variations in this gene are of high pharmacogenetic importance. Because these changes can alter the enzyme’s activity, low enzyme activity can lead to adverse drug reactions. This phenotype is associated with drugs with narrow therapeutic windows. Some of the genetic variants associated with poor CYP2C9 activity include R144C and I359L.
Despite its high pharmacological activity, teriflunomide has also been linked to various side effects. It has been associated with an expanded chance of ILD. ILD can occur acutely or throughout the treatment, and the clinical presentation is variable. For this cause, it is vital to follow patient labeling carefully. Further, patients with a history of liver disease should avoid teriflunomide if they are pregnant or planning to become pregnant.
A lack of evidence suggests
Although a lack of evidence suggests that non-white patients are not more susceptible to teriflunomide than white individuals, a recent study involving non-white patients confirmed that the drug is safe for children with RRMS. The drug is known to be highly bioavailable and slow to reach steady-state concentrations. The estimated AUC accumulation ratio was 34 times greater in patients with severe renal impairment than in non-white patients.
The CYP2C9 enzyme metabolizes teriflunomide and is involved in rapidly eliminating teriflunomide in the blood. This accelerated elimination process is followed by a prolonged period of up to two years. If this is not the case, the drug could cause MRHD in the mother. However, this is unlikely to occur in pregnant women.
Reduce sperm count in male rats
Although teriflunomide has been shown to reduce sperm count in male rats, there is no evidence to support this. However, it has been reported to be embryotoxic and teratogenic in rabbits. Teriflunomide is also adverse for pregnant women during gestation and lactation. Teriflunomide has been used successfully for the treatment of relapsing forms of MS.
In vivo, teriflunomide inhibits both BCRP and OATP1B1/1B3. Hence, adjusting the rifampin dosage or cefaclor if you plan to use them together is essential. CYP2C9 metabolizes teriflunomide to R-hydroxywarfarin.