RESUMEN
A high performance liquid chromatographic assay was developed for plasma and urine levels measurement of viqualine. The assay was used to study the disposition of 25 mg intravenous and oral single doses in five healthy subjects. Two exponential terms were required to describe the disposition of the drug after intravenous and oral administration. The bioavailability of oral viqualine averaged 80%. The mean apparent half-life was 12.1 +/- 1.9 and 11.9 +/- 1.4 h (mean +/- s.e.m., n = 5) after 25 mg I.V. and oral dose respectively. The apparent volume of distribution (Vdss) were 1578 +/- 132 1 (after I.V. administration) and 1572 +/- 201 1 (after oral administration). The body and renal clearances were respectively 1.56 +/- 0.31 1.h-1. kg-1 and 1.57 +/- 0.31 1.h-1. kg-1, after 25 mg bolus I.V.
Asunto(s)
Antidepresivos/metabolismo , Quinolinas/metabolismo , Administración Oral , Adulto , Antidepresivos/sangre , Disponibilidad Biológica , Femenino , Semivida , Humanos , Inyecciones Intravenosas , Cinética , Masculino , Quinolinas/sangreRESUMEN
PK 5078 is a recently developed compound which inhibits specifically the neuronal reuptake of serotonin and enhance its release. PK 5078 was administered to healthy male volunteers in single and multiple oral doses and the effects on platelet serotonin uptake and content were examined. A significant dose-related inhibition of 3H-serotonin uptake by platelets was observed following single oral doses of PK 5078 (25-150 mg), with maximal inhibition at 75 mg. This was evident 2 h after dosing and was still marked after 10 h. Plasma collected from the subjects after dosing also had a considerable dose-related effect on the uptake of 3H-serotonin by untreated platelets. No significant alteration in platelet serotonin content was observed after single doses of PK 5078. When PK 5078 (50 mg) was administered twice daily for 9 days there was a rapid and sustained reduction in 3H-serotonin uptake by platelets, which returned to pretreatment levels 2 days after discontinuation of the drug. A similar response was observed when plasma from these subjects was incubated with untreated platelets. The rate of depletion of endogenous platelet serotonin was much slower with minimum levels being attained on the morning after the final dose. The recovery following withdrawal was also slow with serotonin levels approaching pre-dose values 14 days after the final dose of PK 5078.
Asunto(s)
Plaquetas/metabolismo , Quinolinas/farmacología , Antagonistas de la Serotonina/farmacología , Serotonina/sangre , Adolescente , Adulto , Plaquetas/efectos de los fármacos , Humanos , Masculino , Quinolinas/efectos adversos , Antagonistas de la Serotonina/efectos adversosRESUMEN
The effects of indalpine (a selective 5-HT uptake inhibitor) on the threshold of lower limb nociceptive flexion reflexes were studied (double blind) in humans. After 3 days' administration, indalpine was found to exert a significant naloxone-reversible depression (threshold increased) of the nociceptive reflexes (naloxone and saline were tested double blind). In contrast, no change was found during treatment with placebo. The functional and therapeutic implications of these results are discussed.