ABSTRACT
The metabolic fate of [14C]-labelled 2 and 4-chlorobenzoic acids (2- and 4-CBA) has been determined in the rat following intraperitoneal (i.p.) administration at 100 mg/kg to male rats. The major route of elimination for both 2-and 4-CBA was urine with > 80%, of the dose recovered in the initial 0-24 h after administration. Glycine conjugation was found to be the dominant metabolic fate for both [14C] 2- and 4-CBA however, the position of chloro substitution had a clear effect on the extent of metabolism via this route with ortho substitution reducing the extent of metabolism via this pathway.
Subject(s)
Chlorobenzoates/pharmacokinetics , Animals , Chlorobenzoates/administration & dosage , Chlorobenzoates/urine , Chromatography, Thin Layer , Feces/chemistry , Glycine/metabolism , Injections, Intraperitoneal , Magnetic Resonance Spectroscopy , Male , Mass Spectrometry , RatsABSTRACT
The pharmacokinetics of Chlormezanone (CM) has been determined after a single oral dose of 400 mg CM in 5 young volunteers (28 y) and in 8 elderly patients (79 y). In the young subjects, CM was rapidly absorbed and distributed, and was slowly eliminated with a half-life of 38 h major metabolites were not detected in plasma or urine. Only 3% of CM was excreted unchanged in urine. In elderly patients absorption was delayed but not reduced; the Cmax and AUC did not differ from those in younger subjects, the elimination rate was reduced compared to the younger subjects (mean 54 h). The increase was in part related to the reduction in renal function and metabolism observed in aging. However, the change in pharmacokinetics was moderate and no adjustment in dosage seems necessary for treatments of limited duration in elderly patients.
Subject(s)
Chlormezanone/pharmacokinetics , Administration, Oral , Adult , Age Factors , Aged , Aged, 80 and over , Chlormezanone/administration & dosage , Chlormezanone/blood , Chlormezanone/urine , Chlorobenzoates/blood , Chlorobenzoates/urine , Female , Humans , Male , Time FactorsABSTRACT
1 A gas-liquid chromatography procedure for the determination of chlorphentermine (I), N-hydroxychlorphentermine (II) and alpha,alpha-dimethyl-alpha-nitro-beta-(4-chlorophenyl)ethane (IV) in urine has been developed. Also methods are reported to determine conjugated II and the total N-oxidized metabolites of I, i.e. II, conjugated II, alpha,alpha-dimethyl-alpha-nitroso-beta-(4-chlorophenyl)ethane (III) and IV in urine. 2 The synthesis of alpha,alpha-dimethyl-alpha-nitroso-beta-(4-chlorophenyl)ethane (III) and its properties are reported. 3 The kinetics of urinary excretion of I and its metabolic products after the oral administration of I to a human subject on separate occasions have been studied. Under normal conditions of urinary pH, metabolism by N-oxidation was the main elimination route of I; acidifying the urine increased the urinary excretion of unchanged I at the expense of the N-oxidized products. 4 The importance of the N-oxidation metabolic route in the distribution of chlorphentermine (I) in man is discussed.
