N-Demethylation and dehalogenation of chlorpromazine (CPZ) were compared in six psychotic inpatients and in rats orally treated for 4 weeks with a daily CPZ dose of 5.4 (mean value) and 20 mg X kg-1 body weight, respectively, by measuring drug and metabolite plasma levels by means of a gas-liquid chromatography-nitrogen/phosphorus detector method. In patients the major plasma metabolite was found to be promazine (PZ), as identified by capillary GC-MS analysis. In rats, on the contrary, PZ represented only a small proportion of the compounds detected in plasma. The mean [PZ]/[CPZ] ratio after 4 weeks of treatment was 1.64 in patients and 0.08 in rats. The relative frequency of the N-demethyl metabolites in plasma, however, was similar in the two species. The mean [N-monodemethylated CPZ]/[CPZ] and [N-didemethylated CPZ]/[CPZ] ratios after 4 weeks of treatment were 0.45 and 0.24 in patients and 0.56 and 0.25 in rats, respectively. These findings suggest that dechlorination of CPZ in psychotic patients represents an important metabolic pathway.

Promazine

Active metabolite

10.1016/s0090-9556(25)08332-1

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Citations (21)

Chlorimipramine-induced phospholipidosis: Biochemical and pharmacokinetic observations in the rat

Pharmacological Research Communications (1983)

G.P. Sgaragli Laura Corte D Gremigni

Phospholipidosis

Clomipramine

10.1016/s0031-6989(83)80009-5

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Citations (15)

Nifedipine-like activity of 2-t-butyl-4-methoxyphenol (BHA) on rat ileum longitudinal muscle preparation

Pharmacological Research (1989)

G.P. Sgaragli Massimo Valoti Mitri Palmi P. Mantovani

10.1016/1043-6618(89)90215-6

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Citations (4)

Pharmacokinetics of diphenhydramine in healthy volunteers with a dimenhydrinate 25 mg chewing gum formulation

Methods and Findings in Experimental and Clinical Pharmacology (2003)

Massimo Valoti Maria Frosini Saverio Dragoni Fabio Fusi G.P. Sgaragli

This pharmacokinetic study evaluated diphenhydramine in the plasma of healthy volunteers after a single 25 mg oral dose of dimenhydrinate (diphenhydramine theophyllinate), corresponding to 12.7 mg diphenhydramine, in a chewing gum formulation. Seven volunteers (4 men, 3 women; age: 26.3 +/- 1.2 years; body weight: 63.1 +/- 4.1 kg; height: 172.4 +/- 4.6 cm) chewed the gum for 1 h. Blood samples (10 ml) were collected at different time intervals up to 24 h. Blood plasma was subsequently processed and analyzed for diphenhydramine content using a GLC method and an NPD detector. Analytical data revealed the following kinetic parameters: AUC(0-24h): 155.2h x ng x ml(-1); AUC(0-infinity): 195.3 h x ng x ml(-1); Mean resident time: 16 h; t(1/2): 10 h; C(max): 14.5 ng x ml(-1); t(max): 2.6 h; and plasma clearance: 9.0 ml x min(-1) x kg(-1). This study indicates that the pharmaceutical formulation employed provided sustained plasma concentrations of diphenhydramine, presumably sufficient to support its clinical efficacy towards motion sickness owing to the almost complete (> 95%) release by the formulation of the active principle. Moreover, the maximal concentrations of diphenhydramine attained in plasma were much lower than the concentration threshold needed to produce drowsiness.

Diphenhydramine hydrochloride

10.1358/mf.2003.25.5.769660

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Citations (19)

Toxicity assessment on trophoblast cells for some environment polluting chemicals and 17β-estradiol

Toxicology in Vitro (2013)

Nicoletta Bechi Giuseppina Sorda Antonella Spagnoletti Jayonta Bhattacharjee Eloísa Amália Vieira Ferro

Trophoblast

Reproductive toxicity

Human chorionic gonadotropin

Viability assay

Nonylphenol