title: Pharmacokinetics and antihypertensive effect of oral pelanserin in renal hypertensive dogs.
abstract: The pharmacokinetics and antihypertensive effect of pelanserin (CAS 2208-51-7), a 5-HT2- and alpha 1-antagonist, were studied during repetitive administration (0.5 mg/kg, p.o., b.i.d.) in renal hypertensive dogs. After the first dose, pelanserin was absorbed reaching a Cmax value of 39.6 +/- 9.01 ng/ml at a tmax of 2.58 +/- 0.74 h. The steady state of plasma levels was reached between the 3rd and 15th doses of pelanserin. Pharmacokinetic parameters calculated after the 47th dose of pelanserin were Cmax(ss) of 147.15 +/- 35.88 ng/ml at a tmax(ss) of 3.17 +/- 1.02 h, AUC(0-12 h) of 593.80 +/- 106.96 ng.h/ml and a terminal half-life of 18.02 +/- 2.94 h. The accumulation ratio determined as Cmin(ss)/Cmin1 was 2.36 +/- 0.43 and was similar to that calculated in basis to the terminal half-life 2.67 +/- 0.37. On the other hand, pelanserin produced blood pressure decrease with two different profiles. After the first dose an acute antihypertensive effect was observed which reached a maximum of 20 mmHg in about 3 h; then blood pressure recovered gradually arriving to basal values at 12 h. When administered repetitively, pelanserin produced a gradual reduction in blood pressure which reached its maximum at 15 days. After the last dose, blood pressure basal values were about 20 mmHg lower than pretreatment levels and remained almost unchanged during 48 h after the last dose. It is concluded that pelanserin pharmacokinetic and pharmacodynamic profiles in dogs are adequate for an antihypertensive agent, therefore this drug possesses potential therapeutic usefulness in the treatment of hypertension.
authors.affiliation: Departamento de Farmacología y Toxicología, Instituto Politécnico Nacional, Mexico City, Mexico.
authors.forename: F J
authors.initials: FJ
authors.lastname: Flores-Murrieta
authors.forename: G
authors.initials: G
authors.lastname: Castañeda-Hernández
authors.forename: E
authors.initials: E
authors.lastname: Hong
mesh_terms: D000818:Animals; D000959:Antihypertensive Agents / Q000493:pharmacokinetics / Q000627:therapeutic use*; D001794:Blood Pressure / Q000187:drug effects; D004285:Dogs; D005260:Female; D006207:Half-Life; D006339:Heart Rate / Q000187:drug effects; D006977:Hypertension, Renal / Q000188:drug therapy* / Q000378:metabolism; D008297:Male; D011799:Quinazolines / Q000493:pharmacokinetics / Q000627:therapeutic use*
chemical_list: D000959:Antihypertensive Agents; D011799:Quinazolines; C043157:pelanserin