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J P Freche

Publications and source records attributed to J P Freche.

2 recordsLinked to original sources

Enzyme immunoassay for flecainide.

In order to develop an enzyme immunoassay (ELISA) for measurement of plasma flecainide levels, we first synthesized flecainide-hemisuccinate-BSA as immunogen. A highly specific antiserum was then raised in rabbits. Enzyme-labelled flecainide was prepared by the mixed anhydride method using hemifumarate-flecainide and horse radish peroxidase. The limit of detection was 10 ng/ml, the method was linear up to 1,000 micrograms/l. The intra and inter-assay variation was 5.1-7.8%. Cross reactivity with various metabolites of flecainide or some chemically related drugs was less than 0.1%. By contrast the cross reaction with some structural analogues achieved 25%. The importance of parts of the aromatic ring structure in immunogenic properties of this drug is discussed.

Antibodies↗

[Variation in the urinary excretion of 6-beta-hydroxycortisol in humans after administration of the new isoquinoline derivative, PK-11195 (52028 RP)].

Among in vivo tests to assess liver drug metabolizing enzyme induction, urinary 6-beta-hydroxycortisol (6-beta-OHF), plasma gamma-glutamyltransferase (GGT) and urinary D-glucaric acid are most frequently proposed. 6-beta-OHF is the most abundant unconjugated metabolite of cortisol in human urine. We measured its elimination during a clinical trial in 16 human healthy volunteers (men and women), these persons being treated by a new isoquinoleine derivative, 52028 RP (PK-11195). This drug is an antagonist of peripheral type benzodiazepine binding sites. Urinary excretion of 6-beta-OHF increased significantly (3.5 fold, p less than 0.01) on the 5th day of treatment (400 mg/day, orally) and remained increased as long as the treatment was continued (15 days). Control values were again observed 5 days after stopping the treatment. Plasma gamma-glutamyltransferase activity and D-glucaric acid urinary elimination are increased more than 2 fold. The data demonstrated that 6-beta-OHF in the most sensitive among the three tests performed to detect a drug metabolism induction, during this clinical trial.

Adult↗