I.J. McGilveray

Effect of Sparteine and Quinidine on the Metabolism of Methoxyphenamine by Cunninghamella Bainieri

1. The fungus C. bainieri, incubated for 7 days with methoxyphenamine alone or in combination with either sparteine or quinidine, gave N-desmethylmethoxyphenamine and its N-acetyl conjugate as major metabolites, while O-desmethylmethoxyphenamine, 5-hydroxymethoxyphenamine and 2-hydroxyamphetamine were produced in lesser amounts. In addition, 1-(2-hydroxyphenyl)-2-aminopropane, 1-hydroxy-1-(2-methoxyphenyl)-2-propanone, beta-hydroxymethoxyphenamine, and 1-(5-hydroxy-2-methoxyphenyl)-2-aminopropane were tentatively identified as minor components of the fungal biotransformation of methoxyphenamine. 2. As observed in mammalian systems, the addition of either sparteine or quinidine decreased the rate and extent of methoxyphenamine biotransformation. 3. C. bainieri may be a useful model for drug interaction studies.

The identification of two new urinary metabolites of fenfluramine in man

1. Metabolism of the anorectic agent, fenfluramine, was studied in man to detect phenolic and/or alcoholic metabolites.2. Two new metabolites identified as 1-(m-trifluoromethylphenyl)-2-propanol and 1-(m-trifluoromethylphenyl)-1,2-propanediol, were detected in human urine by g.l.c. and g.l.c.-mass spectrometry.

Simultaneous determination of disopyramide and its mono-N-dealkyl metabolite in plasma and urine by high-performance liquid chromatography.

A high-performance liquid chromatographic procedure is described for the determination of disopyramide and its mono-N-dealkyl metabolite which offers simplicity of extraction with excellent selectivity, sensitivity and reproducibility. The drug and metabolite, following basic diethyl ether extraction and back-extraction with acetic acid, are injected into a reversed-phase high-performance liquid chromatographic column and the absorbance of the eluate measured at 254 nm. Detectability limits of 0.05 micrograms/ml were obtained with both compounds, and studies of the reproducibility, precision, recovery, stability during storage and effect of time in separating plasma from erythrocytes are described. Applications of this high-performance liquid chromatographic procedure to plasma samples from patients on disopyramide therapy and to plasma and urine from a healthy dog administered single doses are reported.

The estimation of quinidine in human plasma by ion pair extraction and high-performance liquid chromatography

A rapid, sensitive, accurate method for determination of quinidine in plasma has been developed using ion-pair extraction and high-performance liquid chromatography. The method, which is capable of distinguishing between quinidine and dihydroquinidine, involves acidification of plasma with perchloric acid, extraction with methyl isobutyl ketone and chromatography of the carbonate-washed extract on a silica gel column with a mobile phase of methylene chloride-hexane-methanol--perchloric acid (60:35:5.5:0.1) followed by fluorometric detection. The procedure is sensitive to below 50 ng/ml (coefficient of variation 6.6%) and compares favourably with a standard spectrofluorometric method when tested with plasma from volunteer subjects.

Evaluation of the in vivo effect of naproxen on zidovudine pharmacokinetics in patients infected with human immunodeficiency virus

Objective: To determine if therapeutic doses of naproxen affect the in vivo disposition of zidovudine.

Application of Statistical Moment Analysis to the Evaluation of Controlled Release Formulations

Riegelman and Collier have recently reviewed (1) the application of first moment analysis, also termed the mean residence time (MRT) method, to the evaluation ofin vivo absorption time using plasma concentration data following single dose administration. The object of the present report is to apply the MRT method, as well as conventional pharmacokinetic techniques, and to evaluate data derived from comparative bioavailability trials of controlled release formulations versus conventional products. The analyses were performed on data from single dose as well as from multiple dose studies conducted in our laboratories.