TASK

DRUG DEVELOPMENT

Arranged by:
Ayu Rahmawati (SBF19840418)
Arifin Chandra (SBF19840420)
istiqomah (SBF191840426)

FACULTY OF PHARMACY
UNIVERSITY OF MIND AND FAITHFUL
Surakarta
2018
 Effect of Genetic Medicine Against Drug Metabolism Carbamazepine

I. preliminary

In general, drug metabolism have a sense of a process of change in chemical drugs caused by
the interaction of drugs with endogenous enzyme system that the end result will increase the polarity of
the drug in the body. During the metabolic processes can occur some of the following:
a. Changes drug into a form that is easier for the metabolites excreted
b. Changes pharmacologically active drug into inactive metabolite form
c. Changes the active drug is excreted into the form of its active metabolite
d. Changes inactive drug into its active metabolite form
e. Modification of a drug into metabolites that have a toxic response.
Pharmacogenomics is the science that is believed to explain that the difference in the response
of each individual to a given drug is closely related to genetic differences of each of the individual. The
more information that is known about the role of genetics in particular drug response at the molecular
level will help researchers in drug development. That requires a device that is able to identify a specific
marker that can predict the occurrence of a negative response or positive response in drug
development based on the genomic technology approach.

II. metabolism Carbamazepine

Carbamazepine is used for the treatment of all kinds of good epilepsy partial or generalized
seizures. When the drug is used, kidney and liver function and hematological parameters should be
monitored. Although the effects of carbamazepine in animals and manusiabanyak similar to the effects
of phenytoin, these two drugs differ in a number of things that are probably important. Carbamazepine
known to produce a therapeutic response in patients with depressive mania, including in some patients
who are not cured with lithium carbonate, in addition to itucarbamazepine has antidiuretic effects
sometimes associated with a reduced concentration of antidiuretic hormone (ADH) in plasma. The
concern is hepatic or renal impairment, pregnant, breastfeeding, avoid sudden termination of medicine,
history of heart disease, glaucoma, a history of hematological reactions to other medications.
Carbamazepine is metabolized in the hearts, in particular by the cytochrome P450 enzyme
CYP3A4 and CYP2C8 isoenzimnya is. Carbamazepine is metabolized by CYP2C8 CYP3A4dan
produce the active metabolite 10,11-epoksikarbamazepin, here are the most plays is CYP3A4,
CYP2C8 only serves to accelerate the work of CYP3A4 to transform into a 10.11-epoksikarbamazepin
carbamazepine. Then converted into 10,11-dihidroksikarbamazepin inactivated by the enzyme
epoksihidrolase to further excreted into the urine in free form and its conjugate. Number of
carbamazepine which is converted to 10,11-epoksikarbamazepin as major metabolic pathway is 30-
50% of the number of doses given to patients during treatment with antiepileptic. 10 11-
epoksikarbamazepin is the active form of carbamazepine while 10,11-dihidroksikarbamazepin is
inactive form of carbamazepine (Tatyana, 1992). Genetic influences have shown that some cytochrome
P450 isoenzymes has a genetic polymorphism, which means that the enzyme cytochrome P450
isoenzymes have different variations of activity. It can be concluded that the genetic influences on drug
response is to increase the rate of carbamazepine biotransformation of drugs in metabolism.

BIBLIOGRAPHY

Tatyana, B., Kudriakova, Lev.A. Sirota, Galina and Vladimir I. Rozova A.Gorkov. 1992.Autoinduction
and Steady-state pharmacokinetics of Carbamazepine and It's Major metabolites, Br.J. Clin. Pharmac.
(1992), 33, 611-615.