Carbamazepine

From PubPK

IUPAC Name
5H-dibenzo[b,f]azepine-5-carboxamide
Physicochemical Properties
CAS number	298-46-4
PubChem	2554
DrugBank	APRD00337
Molecular Formula	C15H12N2O
Molecular Weight (g/mol)	236.26858
logP	2.3
H-Bond Donor	1
H-Bond Acceptor	1
Polar Surface Area (Å2)	46.3

Carbamazepine is an anticonvulsant used to control grand mal and psychomotor or focal seizures.

Contents 1 Trade Names 2 In Vitro Metabolism & Transport 2.1 Metabolism 2.2 Transport 3 Pharmacokinetics 3.1 Summary of Pharmacokinetic Parameters 3.2 Pharmacokinetics in Preclinical Animals 3.3 Pharmacokinetics in Humans 3.3.1 Absorption 3.3.2 Distribution 3.3.3 Metabolism 3.3.4 Excretion 3.4 Factors Influencing Pharmacokinetics 3.4.1 Age 3.4.2 Gender 3.4.3 Ethnicity 3.4.4 Diseases 3.4.5 Formulation 3.4.6 Food 4 Drug Interactions 4.1 Effects on Other Drugs 4.2 Effects by Other Drugs 5 See also 6 External links 7 References

Trade Names

• Carbatrol
• Equetro
• Tegretol

In Vitro Metabolism & Transport

Metabolism

Carbamazepine undergoes extensive metabolism, with the initial oxidative pathways being catalysed mainly by CYP3A4 (Kerr et al. 1994).

CYP	Substrate	Inhibitor	Inducer	UGT	Substrate	Inhibitor	Inducer
CYP1A1				UGT1A1
CYP1A2				UGT1A3
CYP1B1				UGT1A4
CYP2A6				UGT1A6
CYP2B6				UGT1A9
CYP2C8				UGT2A1
CYP2C9				UGT2A2
CYP2C19				UGT2A3
CYP2D6				UGT2B4
CYP2E1				UGT2B7
CYP2J2				UGT2B10
CYP3A4	Yes1			UGT2B11
CYP3A5				UGT2B15
CYP3A7				UGT2B17

References: ¹Kerr et al., 1994;

Transport

ABC	Substrate	Inhibitor	Inducer	SLC	Substrate	Inhibitor	Inducer
ABCB1 (MDR1)	NO1			SLC10A1 (NTCP)
ABCB4 (MDR3)				SLC10A2 (NTCP2)
ABCB11 (BSEP)				SLC15A1 (PEPT1)
ABCC1 (MRP1)				SLC15A2 (PEPT2)
ABCC2 (MRP2)				SLC16A1 (MCT1)
ABCC3 (MRP3)				SLC16A4 (MCT5)
ABCC4 (MRP4)				SLC22A1 (OCT1)
ABCC5 (MRP5)				SLC22A2 (OCT2)
ABCC6 (MRP6)				SLC22A3 (OCT3)
ABCC10 (MRP7)				SLC22A4 (OCTN1)
ABCC11 (MRP8)				SLC22A5 (OCTN2)
ABCG2 (BCRP)				SLC22A6 (OAT1)
				SLC22A7 (OAT2)
				SLC22A8 (OAT3)
				SLC22A9 (UST3)
				SLC22A11 (OAT4)
				SLC28A3 (CNT3)
				SLCO1A2 (OATP-A)
				SLCO1B1 (OATP-C)
				SLCO1B3 (OATP8)
				SLCO1C1 (OATP-F)
				SLCO2B1 (OATP-B)
				SLCO3A1 (OATP-D)
				SLCO4A1 (OATP-E)
				SLCO4C1 (OATP-H)

References: ¹Owen et al. 2001;

Pharmacokinetics

Summary of Pharmacokinetic Parameters

CL_iv: total plasma clearance after iv administration; CL_R: renal clearance of drug from the plasma; Vss: volume of distribution at steady state; t_1/2: elimination half-life; F_oral: oral bioavailability; f_a: fraction of administered dose absorbed; E_G: gut extraction ratio; E_H: hepatic extraction ratio; fu: unbound fraction of drug in plasma; b/p: blood-to-plasma ratio

	Mouse	Rat	Rabbit	Dog	Monkey	Human
CLiv (mL/min/kg)
CLR (mL/min/kg)
Vss (L/kg)
t1/2β (h)
Foral (%)
fa
EG (%)
EH (%)
fu (%)
b/p

References: ¹

Pharmacokinetics in Preclinical Animals

to be updated

Pharmacokinetics in Humans

Absorption

to be updated

Distribution

to be updated

Metabolism

to be updated

Excretion

to be updated

Factors Influencing Pharmacokinetics

Age

to be updated

Gender

to be updated

Ethnicity

to be updated

Diseases

to be updated

Formulation

to be updated

Food

to be updated

Drug Interactions

Carbamazepine is a well-known inducer of CYP3A4.

Effects on Other Drugs

• Quetiapine Carbamazepine (600mg daily) decreased quetiapine plasma C_max by 80% and increased its clearance (CL/F) to 7.5-fold (Grimm et al. 2006).

Effects by Other Drugs

to be updated

See also

• Oxcarbazepine

External links

• PubChem - Carbamazepine
• RxList - Tegretol
• DrugBank - Carbamazepine
• Wikipedia - Carbamazepine
• Carbatrol
• Equetro

References

• Grimm SW, Richtand NM, Winter HR, Stams KR, and Reele SB (2006) Effects of cytochrome P450 3A modulators ketoconazole and carbamazepine on quetiapine pharmacokinetics Br J Clin Pharmacol 61:58–69.
• Kerr BM, Thummel KE, Wurden CJ, Klein SM, Kroetz DL, Gonzalez FJ, Levy RH (1994) Human liver carbamazepine metabolism – role of CYP3A4 and CYP2C8 in 10,11-epoxide formation Biochem Pharmacol 47:1969–79.
• Owen A, Pirmohamed M, Tettey JN, Morgan P, Chadwick D, Park BK (2001) Carbamazepine is not a substrate for P-glycoprotein Br J Clin Pharmacol 51:345-9.