Цитохром Р450, скорее, дополняющая теория.
как я понимаю с цитохромом Р450 взаимодействуют куча лекарств.
Взаимодействия с ПЭП и другими лекарствами подробно описаны для EPIDIOLEX. Там есть вальпроаты, клобазам, диазепам и тд
https://www.epidiolex.com/sites/default/files/EPIDIOLEX_Full_Prescribing_Information.pdf"DRUG INTERACTIONS
7.1 Effect of Other Drugs on EPIDIOLEX
Moderate or Strong Inhibitors of CYP3A4 or CYP2C19
EPIDIOLEX is metabolized by CYP3A4 and CYP2C19. Therefore, coadministration
with a moderate or strong inhibitor of CYP3A4 or CYP2C19 will increase
cannabidiol plasma concentrations, which may result in a greater risk of adverse
reactions [see Clinical Pharmacology (12.3)]. Consider a reduction in EPIDIOLEX
dosage when coadministered with a moderate or strong inhibitor of CYP3A4 or
CYP2C19.
Strong CYP3A4 or CYP2C19 Inducers
Coadministration with a strong CYP3A4 or CYP2C19 inducer will decrease
cannabidiol plasma concentrations, which may lower the efficacy of EPIDIOLEX
[see Clinical Pharmacology (12.3)]. Consider an increase in EPIDIOLEX dosage
(based on clinical response and tolerability) when coadministered with a strong
CYP3A4 or CYP2C19 inducer.
7.2 Effect of EPIDIOLEX on Other Drugs
UGT1A9, UGT2B7, CYP1A2, CYP2B6, CYP2C8, CYP2C9 and CYP2C19 Substrates
In vitro data predict drug-drug interactions with CYP1A2 substrates (e.g.,
theophylline, caffeine), CYP2B6 substrates (e.g., bupropion, efavirenz), uridine
5' diphospho-glucuronosyltransferase 1A9 (UGT1A9) (e.g., diflunisal, propofol,
fenofibrate), and UGT2B7 (e.g., gemfibrozil, lamotrigine, morphine, lorazepam)
when coadministered with EPIDIOLEX. Coadministration of EPIDIOLEX is also
predicted to cause clinically significant interactions with CYP2C8 and CYP2C9
(e.g., phenytoin) substrates. Because of potential inhibition of enzyme activity,
consider a reduction in dosage of substrates of UGT1A9, UGT2B7, CYP2C8, and
CYP2C9, as clinically appropriate, if adverse reactions are experienced when
administered concomitantly with EPIDIOLEX. Because of potential for both
induction and inhibition of enzyme activity, consider adjusting dosage of
substrates of CYP1A2 and CYP2B6, as clinically appropriate.
Sensitive CYP2C19 Substrates
In vivo data show that coadministration of EPIDIOLEX increases plasma
concentrations of drugs that are metabolized by (i.e., are substrates of) CYP2C19
(e.g., diazepam) and may increase the risk of adverse reactions with these
substrates [see Clinical Pharmacology (12.3)]. Consider a reduction in dosage of
sensitive CYP2C19 substrates, as clinically appropriate, when coadministered
with EPIDIOLEX.
Clobazam
Coadministration of EPIDIOLEX produces a 3-fold increase in plasma
concentrations of N-desmethylclobazam, the active metabolite of clobazam (a
substrate of CYP2C19) [see Clinical Pharmacology (12.3)]. This may increase the
risk of clobazam-related adverse reactions [see Warnings and Precautions (5.1,
5.2)]. Consider a reduction in dosage of clobazam if adverse reactions known to
occur with clobazam are experienced when co-administered with EPIDIOLEX.
7.3 Concomitant Use of EPIDIOLEX and Valproate
Concomitant use of EPIDIOLEX and valproate increases the incidence of liver
enzyme elevations [see Warnings and Precautions (5.1)]. Discontinuation or
reduction of EPIDIOLEX and/or concomitant valproate should be considered.
Insufficient data are available to assess the risk of concomitant administration of
other hepatotoxic drugs and EPIDIOLEX.
7.4 CNS Depressants and Alcohol
Concomitant use of EPIDIOLEX with other CNS depressants may increase the risk
of sedation and somnolence [see Warnings and Precautions (5.2)]. "
