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I would like to know which Phase I reactions (chlorpromazine) can undergo during metabolism and, if possible, the name of metabolites. Thank You very much martin
by Martin in UK, 01/11/2008

Chlorpromazine hydrochloride
Chlorpromazine hydrochloride (Thorazine)
Chlorpromazine hydrochloride
(klor- PROH-mah-zeen)
Pregnancy Category: C Chlorprom Chlorpromanyl Largactil Novo-Chlorpromazine Thorazine (Rx)

Classification: Antipsychotic, dimethylamino-type phenothiazine

See Also: See also Antipsychotic Agents, Phenothiazines .

Action/Kinetics: Has significant antiemetic, hypotensive, and sedative effects; moderate anticholinergic and extrapyramidal effects. Peak plasma levels: 2-3 hr after both PO and IM administration. t 1/2 (after IV, IM): Initial, 4-5 hr; final, 3-40 hr. Extensively metabolized in the intestinal wall and liver; certain of the metabolites are active. Steady-state plasma levels (in psychotics): 10-1,300 ng/mL. After 2-3 weeks of therapy, plasma levels decline, possibly because of reduction in drug absorption and/or increase in drug metabolism.

Uses: Acute and chronic psychoses, including schizophrenia; manic phase of manic-depressive illness. Acute intermittent porphyria. Preanesthetic, adjunct to treat tetanus, intractable hiccoughs, severe behavioral problems in children, and N&V. Investigational: Treatment of phencyclidine psychosis. IM or IV to treat migraine headaches.

Special Concerns: Use during pregnancy only if benefits outweigh risks. Safety for use during lactation has not been established. PO dosage for psychoses and N&V has not been established in children less than 6 months of age.

Laboratory Test Alterations: Possible plasma cholesterol.

Additional Drug Interactions: Epinephrine / Chlorpromazine peripheral vasoconstriction and may reverse action of epinephrine Norepinephrine / Chlorpromazine pressor effect and eliminates bradycardia due to norepinephrine Valproic acid / Effect of valproic acid due to clearance

How Supplied: Chlorpromazine hydrochloride: Capsule, Extended Release: 30 mg, 75 mg, 150 mg; Concentrate: 30 mg/mL, 100 mg/mL; Injection: 25 mg/mL; Rectal Suppository: 25 mg, 100 mg; Syrup: 10 mg/5 mL; Tablet: 10 mg, 25 mg, 50 mg, 100 mg, 200 mg

?Tablets, Extended-Release Capsules, Oral Concentrate, Syrup Outpatients, general uses.
Adults: 10 mg t.i.d.-q.i.d. or 25 mg b.i.d.-t.i.d. For more serious cases, 25 mg t.i.d. After 1 or 2 days, increase daily dose by 20 to 50 mg semiweekly, until client becomes calm and cooperative. Maximum improvement may not be seen for weeks or months. Continue optimum dosage for 2 weeks; then, reduce gradually to maintenance levels (200 mg/day is usual). Up to 800 mg/day may be needed in discharged mental clients.
Psychotic disorders, less acutely disturbed.
Adults and adolescents: 25 mg t.i.d.; dosage may be increased by 20-50 mg/day q 3-4 days as needed, up to 400 mg/day.
Behavioral disorders in children.
Outpatients: 0.5 mg/kg (0.25 mg/lb) q 4-6 hr, as needed. Hospitalized: Start with low doses and increase gradually. For severe conditions: 50-100 mg/day. In older children, 200 mg or more/day may be needed.
Adults and adolescents: 10-25 mg (of the base) q 4 hr; dosage may be increased as needed. Pediatric: 0.55 mg/kg (15 mg/m 2) q 4-6 hr.
Preoperative sedation.
Adults and adolescents: 25-50 mg 2-3 hr before surgery. Pediatric: 0.5 mg/kg (15 mg/m 2) 2-3 hr before surgery.
Hiccoughs or porphyria.
Adults and adolescents: 25-50 mg t.i.d.-q.i.d.
?IM Psychotic disorders, acutely manic or disturbed.
Adults, initial: 25 mg. If necessary, give an additional 25-50 mg in 1 hr. Increase gradually over several days; up to 400 mg q 4-6 hr may be needed in severe cases. Client usually becomes quiet and cooperative within 24-48 hr. Substitute PO dosage and increase until client is calm (usually 500 mg/day). Pediatric, over 6 months: 0.5 mg/kg (0.25 mg/lb) q 6-8 hr as needed. Do not exceed 75 mg/day in children 5 to 12 years of age or 40 mg/day in children up to 5 years of age.
Intraoperative to control N&V.
Adults: 12.5 mg; repeat in 30 min if necessary and if no hypotension occurs. Pediatric: 0.25 mg/kg (0.125 mg/lb); repeat in 30 min if necessary and if no hypotension occurs.
Preoperative sedative.
Adults: 12.5-25 mg 1-2 hr before surgery. Pediatric: 0.5 mg/kg (0.25 mg/lb) 1-2 hr before surgery.
Adults: 25-50 mg (base) t.i.d.-q.i.d.
Acute intermittent porphyria.
Adults: 25 mg q 6-8 hr until client can take PO therapy.
Adults: 25-50 mg t.i.d.-q.i.d., usually with barbiturates.
?IV Intraoperative to control N&V.
Adults: 2 mg/fractional injection at 2-min intervals, not to exceed 25 mg (dilute with 1 mg/mL saline). Pediatric: 1 mg/fractional injection at 2-min intervals, not to exceed IM dosage (always dilute to 1 mg/mL saline).
Adults: 25-50 mg diluted to 1 mg/mL with 0.9% NaCl injection and given at a rate of 1 mg/min. Pediatric: 0.5 mg/kg diluted to 1 mg/mL with 0.9% NaCl injection and given at a rate of 1 mg/2 min. Do not exceed 40 mg/day in children who weigh up to 23 kg (50 lb) or 75 mg/day in children who weigh 23-45 kg (50-100 lb).
?Suppositories Behavioral disorders in children.
1 mg/kg (0.5 mg/lb) q 6-8 hr, as needed.

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