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Impaired absorption of desmethyldiazepam from clorazepate by magnesium aluminum hydroxide
Author(s) -
Shader Richard I.,
Georgotas Anastasios,
Greenblatt David J.,
Harmatz Jerold S.,
Allen Marcia Divoll
Publication year - 1978
Publication title -
clinical pharmacology and therapeutics
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.941
H-Index - 188
eISSN - 1532-6535
pISSN - 0009-9236
DOI - 10.1002/cpt1978243308
Subject(s) - antacid , magnesium , chemistry , hydroxide , crossover study , volunteer , absorption (acoustics) , pharmacology , chromatography , medicine , inorganic chemistry , biochemistry , placebo , physics , alternative medicine , organic chemistry , pathology , acoustics , agronomy , biology
Ten healthy volunteers ingested single 15‐mg doses of clorazepate dipotassium (CZP) with 60 ml of water, or with 60 ml of magnesium aluminum hydroxide (Maalox), on two occasions in a randomized, two‐way crossover study. Plasma concentrations of desmethyldiazepam (DMDZ) were determined in multiple sampies drawn during 48 hr after each dose. Mean kinetic variables for DMDZ in CZP‐water and CZP‐magnesium aluminum hydroxide treatment conditions, respectively, were: peak measured concentration, 273 and 188 ng/ml (p < 0.001); time of peak concentration, 1.8 and 2.8 hr after dose (p < 0.01); apparent absorption half‐life, 14.8 and 30.7 min (p < 0.02); area under the 48‐hr plasma concentration curve, 6,028 and 5,433 ng/ml · hr (p < 0.02). Self‐rated sensations offeeling “spacey,” “thinking slowed down,” and of generalized sedation, were reported with both treatment conditions, but these subjective effects occurred earlier and were more profound when CZP was taken with water as opposed to magnesium aluminum hydroxide. Thus administration of single doses of CZP with usual doses of a commonly prescribed antacid reduces the rate and extent of appearance in blood of DMDZ (the compound responsible for clinical activity) and attenuates self‐rated clinical effects.