RESUMO
A combination of trimethoprim (TMP) and sulfamethopyrazine (SMP) was administered to six healthy volunteers for 8 days, according to the proposed therapeutic repeated dose schedule. The weak base TMP (pKa = 7.3) and the weak acid SMP (pKa = 6.1) were measured simultaneously in serum and saliva, both under normal conditions and after stimulation of saliva flow. The flow of saliva was stimulated by chewing plastic material in order to obtain saliva at a pH close to the normal plasma pH of 7.4. This procedure excluded pH-dependent distribution effects. Under these experimental conditions a highly significant correlation was observed between the serum and saliva concentrations of both drugs, with very small inter- and intraindividual variations. Substantial agreement was found between the saliva:serum concentration ratio and the fractions of both drugs not bound to plasma protein. Some discrepancies were noted, probably due to minor shifts in saliva pH during the collection period.
Assuntos
Saliva/metabolismo , Sulfaleno/metabolismo , Sulfanilamidas/metabolismo , Trimetoprima/metabolismo , Adulto , Proteínas Sanguíneas/metabolismo , Combinação de Medicamentos , Humanos , Concentração de Íons de Hidrogênio , Ligação Proteica , Sulfaleno/sangue , Trimetoprima/sangueRESUMO
The PRL response to TRH was evaluated before and after acute administration of metergoline, an antiserotonin drug, in healthy subjects. The drug was given to two groups of 6 subjects each, at the dose of 4 and 8 mg respectively, either po or by im route. Metergoline significantly inhibited the PRL response to TRH; no significant difference was found between the two doses and the administration routes. Although these findings suggest that the drug may directly inhibit lactotropic cells, an action of metergoline on central nervous system to stimulate PIF or to inhibit PRF release cannot be ruled out, and might as well explain the inhibition of the PRL response to TRH.
