DƯỢC LÍ Goodman & Gilman's The Pharmacological Basis of Therapeutics 12th, 2010

Table 6–2
Major Reactions Involved in Drug Metabolism
REACTION
EXAMPLES
I. Oxidative reactions
N-Dealkylation RNHCH 3
→ RNH 2
+ CH 2
O Imipramine, diazepam, codeine,
erythromycin, morphine, tamoxifen,
theophylline, caffeine
O-Dealkylation ROCH 3
→ ROH + CH 2
O Codeine, indomethacin, dextromethorphan
Aliphatic RCH 2
CH 3
→ RCHOHCH 3
Tolbutamide, ibuprofen, phenobarbital,
hydroxylation
meprobamate, cyclosporine, midazolam
Aromatic
Phenytoin, phenobarbital, propanolol,
hydroxylation
ethinyl estradiol, amphetamine, warfarin
N-Oxidation
RNHOH
RNH 2
N OH
Chlorpheniramine, dapsone, meperidine
R 1
R 2
NH
R 1
R 2
S-Oxidation
Deamination
R CH
R 1
R 1
S
R 2 R 2
S O
OH
RCHCH 3
NH 2
O
C
R C CH 3 + NH 3
NH 2
3
Cimetidine, chlorpromazine, thioridazine,
omeprazole
Diazepam, amphetamine
II. Hydrolysis reactions Carbamazepine (see Figure 6-4)
O
R 1 COR 2
O
R 1 CNHR 2
R 1 COOH
R 1 COOH
+
+
R 2 OH
R 2 NH 2
Procaine, aspirin, clofibrate, meperidine,
enalapril, cocaine
Lidocaine, procainamide, indomethacin
III. Conjugation reactions
Glucuronidation
R +
COOH
OH
COOH
O O
OH
R
+ UDP
Acetaminophen, morphine, oxazepam,
lorazepam
OH
O
OH
UDP
OH
OH
Sulfation
Acetylation
PAPS
+ ROH R O SO 2 OH +
Acetaminophen, steroids, methyldopa
Sulfonamides, isoniazid, dapsone,
clonazepam
Methylation RO-, RS-, RN- + AdoMet → RO-CH 3
+ AdoHomCys L-Dopa, methyldopa, mercaptopurine,
captopril
Glutathionylation GSH + R → R-GSH Adriamycin, fosfomycin, busulfan
PAPS, 3′-phosphoadenosine-5′ phosphosulfate; PAP 3’-phosphoadenosine-5’-phosphate.
PAP
CoAS CO CH 3 + RNH 2 RNH CO CH 3 + CoA-SH