Usefulness of salivary drug monitoring for detectign efflux transporter overexpression

PIETRO FAGIOLINO; MARTA VÁZQUEZ; CECILIA MALDONADO; MARÍA ESPERANZA RUIZ; MARÍA GUILLERMINA VOLONTÉ; SANDRA OROZCO-SUÁREZ; ALBERTO LAZAROWSKI

CURRENT PHARMACEUTICAL DESIGN.

BENTHAM SCIENCE PUBL LTD

Lugar: Oak Park; Año: 2013 vol. 19 p. 6701 - 6708

1381-6128

Venous (V) / artery (A) concentration ratio of a drug could be a reliable index of its clearance (CL) if measurements of plasma concentration were performed during a period of time where the absorption process was not longer operative, then during a pure elimination phase. A novel subrogate using two protocolized saliva samples sequentially collected (first, S1, and second, S2) was designed in order to replace V and A free plasma drug concentrations, respectively. Two drugs, phenytoin (PHT) and carbamazepine (CBZ), which are well-known for their inducer properties and their dose-dependent CL variations, were studied. A multicentre two-phase collaborative study was done. The first phase was performed with healthy volunteers (single dose) and the second phase was carried out with epileptic patients under CBZ or PHT monotherapy (multiple doses). S1/S2 saliva drug concentration ratio was sensitive enough for detecting systemic CL changes from single to multiple dose administrations, and because of daily dose modifications. Both CBZ and PHT would modify their bioavailability and clearance by inducing efflux transporter throughout chronic treatments. Sex-related pharmacokinetic impacts of this inductive effect were also observed.