No abstract

The demetylation of imipramine and clomipramine was studied after administration by different routes of single doses of clomipramine hydrochloride and multiple doses of clomipramine as well as imipramine hydrochloride. Five healthy volunteers received 1 mg of clomipramine hydrochloride/kg body weight as single oral and intramuscular doses on different occasions for the purpose of studying the plasma levels of clomipramine and the desmethylclomipramine formed. Desmethylclomipramine was found in the plasma in four of the subjects after oral intake but only in one subject after intramuscular injection. The peak levels of clomipramine were considerably higher after intramuscular than after oral administration. The half-lives of clomipramine after oral administration ranged from 11.6-35.8 h (M = 20.8 +/- 4.0) and after intramuscular administration from 20.1--39.6 h (M = 24.7 +/- 3.7). Twenty subjects received either imipramine or clomipramine both orally and intramuscularly during a period of 3 weeks in a crossover design. The plasma levels of imipramine and clomipramine and their demethylated metabolites desipramine and desmethylclomipramine were determined during the treatment. The ratio between the plasma level of the parent drug and its demethylated metabolite was on average twice as high during intramuscular as during oral treatment.

With the object of studying the kinetics of imipramine and desipramine five healthy volunteers received single intramuscular, oral and intravenous doses and multiple oral doses of imipramine hydrochloride on different occasions. Two of the volunteers also received single intramuscular and oral doses of desipramine hydrochloride. Great interindividual differences were noted in the plasma concentrations of imipramine and the formed desipramine after single doses of imipramine hydrochloride. In all subjects more desipramine was formed after oral than after parenteral adminstration of imipramine. The bioavailability of an orally administered dose of imipramine ranged between 29.5 and 54.7%. The concentration of imipramine was generally lower in the blood cells than in the plasma, unlike the concentration of desipramine which was considerably higher in the blood cells. The half-lives of imipramine ranged from 4.0-17.6 hrs (M = 7.6 +/- 2.5) after single oral doses and between 9.2 and 20.2 hrs (M = 14.0 +/- 1.9) after multiple oral doses. The half-lives of the formed desipramine ranged between 13.5 and 61.5 hrs (M = 29.9 +/- 8.7) after multiple oral doses of imipramine hydrochloride. The observed mean steady-state plasma concentration after multiple oral doses of imipramine hydrochloride, 50 mg t.i.d. varied from 21.4-69.0 mug/1 (M = 38.2 +/- 8.7) for imipramine and from 33.7-136.0 mug/1 (M 72.3 +/- 19.5) for desipramine. The great difference in the ability to form desipramine after oral and parenteral administration of imipramine hydrochloride may have therapeutic consequences as imipramine and desipramine have differing pharmacological properties.

SUMMARY Four boys with the combination of infantile autism and the fragile‐X syndrome were given oral folic acid and placebo, according to a double‐blind crossover design. One boy's behaviour appeared to improve on folic acid, but another boy did not seem to be affected at all. For the remaining two boys the results were equivocal. Further study of folic acid in the treatment of autistic boys with the fragile‐X syndrome is warranted. RESUME Acide folique en appoint dans le traitement des enfants presentant un autisme en association avec un syndrome de chromosome X fragile (AFRAX) Quatre garçons presentant un autisme infantile et un syndrome de chromosome X fragile ont recu de l'acide folique et un placebo selon un schema de double aveugle croisé. L'un des garçons a paru s'améliorer sur le plan du comportement avec l'acide folique tandis qu'un autre garcon ne paraissait resentir aucun effet. Les résultats étaient discutables chez les deux autres garçons. D'autres travaux sur l'acide folique dans le traitement des garçons autistiques avec syndrome du chromosome X fragile sont souhaités. ZUSAMMENFASSUNG Folsäure für die Behandlung von Kindern mit Autismus und fragilem X‐Chromosom‐Syndrom Vier Knaben mit einer Combination eines infantilen Autismus mit einem fragilen X‐Chromosom‐Syndrom wurden in einer gekreuzten Doppelblindstudie oral mit Folsäure bzw. einem Placebo behandelt. Ein Junge schien sich durch die Folsäure Therapie im Verhalten zu bessern, während bei einem anderen überhaupt keine Wirkung festzustellen war. Bei den zwei weiteren Jungen waren die Ergebnisse ungewiß. Es warden weitere Untersuchungen über die Wirkung der Folsäure in der Behandlung autistischer Jungen mit fragilem X‐Chromosom durchgefürt. RESUMEN Acido fólico como coadyuvante en el tratamiento de niños con autismo Síndrome de X frágil (AFRAX) Cuatro muchachos con la combinatión de autismo infantil y sindrome de X frágil, recibieron ácido fólico y un placebo siguiendo un esquema cruzado doble ciego. Un muchacho mejoró en su comportamiento con ácido fólico, mientras que otro no pareció que se afectaba en absolute En los restantes dos muchachos, los resultados eran equivocos. Se considera necesario un estudio más amplio del uso del ácido fólico en el tratamiento de niños autísticos con sindrome de X frágil.