Isotretinoin versus placebo in the treatment of cystic acne. A randomized double-blind study.

Thirty-three patients with treatment-resistant cystic and conglobate acne entered a randomized, double-blind protocol testing the efficacy of isotretinoin versus placebo. There was an overall 57% increase in the number of cystic lesions in seventeen patients who initially received placebo. Sixteen of these seventeen patients then received isotretinoin, with a resultant 98% improvement. The sixteen patients who had been randomly assigned to receive initial therapy with isotretinoin had a 95% improvement. Twenty-seven of the thirty-two patients treated with isotretinoin cleared completely. The average maximum dosage of isotretinoin received by these patients was 1.2 mg/kg/day. Eighteen patients received only one 4-month course of isotretinoin. Fifteen patients received two courses. These included twelve patients with predominantly truncal acne who responded partially to the first course, and three patients who had cleared completely after one course of therapy but had mild relapses after an average of six months off of treatment. All patients are now in remission averaging 38 months in duration. Skin biopsies and quantitative measurement of sebum production during therapy indicated a profound inhibition of sebaceous gland size and function, which may be central to the mechanism of action of isotretinoin in acne.

Relationship between diazepam dose, plasma level, age, and central nervous system depression.

Patients undergoing elective cardioversion for treatment of arrhythmias were premedicated with diazepam. The dose was individualized to achieve a degree of central nervous system CNS) depression characterized by response to painful but not vocal stimulation. Promptly following each cardioversion, blood was drawn and the plasma diazepam concentration was measured by gas chromatography. The plasma levels varied as widely as the diazepam doses so that there was no fixed plasma level of diazepam associated with the degree of CNS depression produced in these patients. However, both the dose of diazepam and the resulting plasma level were inversely correlated to age, indicating that age is a critical factor in the use of diazepam for cardioversion premedication; elderly are more sensitive to the depressant effects of this drug than the young.

Further studies on medazepam metabolism in the rat.

Previous studies with 9000g supernatant fractions of rat liver revealed that the 1,4-benzodiazepine, medazepam, was converted to N-desmethyldiazepam by a series of reactions including hydroxylation, N-demethylation, and dehydrogenation. The present study was designed to determine if the pathway via diazepam as intermediate, which is one of three possible pathways, is the major route in vivo in the rat for N-desmethyldiazepam formation from medazepam. Measurement of the levels of labeled drug and metabolites in blood, brain, lung, heart, and muscle 5 min after the oral administration of approximately equivalent doses of [14C]medazepam hydrochloride, [14C]diazepam, or N-desmethyl[14C]medazepam revealed that each drug was both rapidly absorbed and oxidatively metabolized in the rat. At 1 hr. the tissue levels of labeled N-desmethyldiazepam were highest after N-desmethyl-[14C]medazepam, intermediate after [14C]medazepam hydrochloride and lowest after [14C]diazepam. These results indicated that in the formation of N-desmethyldiazepam from medazepam in the rat there is a substantial preference for the pathway via N-desmethylmedazepam over that in which diazepam is an intermediate. From consideration of the limited data available, it is suggested that this same preference in pathways may also hold true in humans.