[Asymptomatic acute cytolytic hepatitis due to fluindione and associated with resistance to treatment: a case report and review of the literature]. / Hépatite aiguë cytolytique asymptomatique à la fluindione s'accompagnant d'une résistance au traitement. A propos d'un cas. Revue de la littérature.

The authors report a case of asymptomatic acute cytolytic hepatitis due to fluindione (Previscan) associated with relative and selective resistance to this drug prescribed as a relay of heparin therapy for deep venous thrombosis following immobilisation of a sprained ankle in a 22 year-old patient. The main complications of oral anticoagulants are bleeding. Very severe immuno-allergic complications, especially hepatic, have been described with phenindione therapy. A review of the literature revealed a very low incidence of fluindione-induced hepatitis (7 cases), only two of which were fully documented since the commercialization of this molecule in 1971. No fatalities were reported: resistance to the treatment seemed to be associated. The exact mechanism (toxicity or immuno-allergy) has not been determined although the fact that fluindione is one of the indanedione family is in favour of the latter hypothesis.

[Nycthemeral changes in plasma concentrations of active nitrate derivatives. Comparison of a single dose of LP 60mg isosobide dinitrate and LP 20mg isosobide dinitrate administered 3 times daily]. / Les variations nycthémérales des concentrations plasmatiques de nitrés actifs. Comparaison du dinitrate d'isosorbide LP 60 mg en monoprise et du dinitrate d'isosorbide LP 20 mg en 3 prises.

The daily plasma level fluctuation is critical in the prevention of tolerance during long-term nitrate therapy. Two dosage regimens of sustained-release isosorbide dinitrate (ISDN) (60 mg tablet once daily vs 20 mg three times daily) were compared at steady state. Comparative bioavailability data of the two forms after single administration in 12 healthy subjects enabled calculation of the steady state blood levels of ISDN, IS-2MN and IS-5MN by simultation of the two regimens. Both achieved the required trough concentration to restore sensitivity to nitrates (100 micrograms/l for IS-5MN), but greater plasma level increases were observed (greater than 200 micrograms/l for IS-5MN), with 60 mg once daily. A parallel, randomised, double-blind, double placebo study involved 126 patients with stable angina, concomitantly receiving beta-blockers and/or calcium inhibitors. Ergometric parameters 4 hours after drug administration and clinical symptoms were compared at inclusion under 20 mg three times daily, and after a 4 week treatment with either dosage. Compared with 20 mg three times daily, the once daily regimen: improved equally the symptoms and ergometric parameters of stable angina in combination therapy; had a similar side-effect profile; enhanced the sensitivity to nitrate 4 hours after administration with regard to the hypotensive effect; the latter may clinically reflect the pharmacokinetic differences between the two regimens. Sixty milligrammes sustained release ISDN once daily may thus avoid nitrate tolerance and improve patient compliance.