title: Pharmacokinetics and anti-emetic efficacy of BRL43694, a new selective 5HT-3 antagonist.
abstract: Twenty patients receiving a variety of emetogenic cytotoxics (including cisplatin in 5) were given a single i.v. infusion of 40 micrograms kg-1 of BRL43694 (as the hydrochloride salt) in successive groups of 3-4 patients between 0-6 hours after chemotherapy. Eleven patients were completely protected from vomiting; 9 had mild to moderate nausea and vomiting, but none severe enough to require alternative anti-emetic 'rescue'. In 4 of the patients in whom BRL43694 was delayed until 4-6 h after chemotherapy, vomiting had already begun; in each case immediate termination of vomiting occurred when BRL43694 was infused. No adverse effects attributable to the anti-emetic were observed. Mean pharmacokinetic parameters in 14 patients in whom plasma assay data are available were: Maximum observed concentration = 30.7 ng ml-1; terminal phase half-life = 8.96 h; total body clearance = 0.376 (1 h-1) kg-1; apparent volume of distribution = 2.85 l kg-1. This study shows BRL43694 to be an effective and well tolerated anti-emetic. Further studies aimed at defining an optimal dose and schedule for use against the most emetogenic cytotoxics are in progress.
authors.affiliation: CRC Department of Medical Oncology, Glasgow.
authors.forename: J
authors.initials: J
authors.lastname: Cassidy
authors.forename: V
authors.initials: V
authors.lastname: Raina
authors.forename: C
authors.initials: C
authors.lastname: Lewis
authors.forename: L
authors.initials: L
authors.lastname: Adams
authors.forename: M
authors.initials: M
authors.lastname: Soukop
authors.forename: W G
authors.initials: WG
authors.lastname: Rapeport
authors.forename: B D
authors.initials: BD
authors.lastname: Zussman
authors.forename: E M
authors.initials: EM
authors.lastname: Rankin
authors.forename: S B
authors.initials: SB
authors.lastname: Kaye
mesh_terms: D000293:Adolescent; D000328:Adult; D000368:Aged; D000970:Antineoplastic Agents / Q000009:adverse effects*; D004361:Drug Tolerance; D005260:Female; D017829:Granisetron; D006207:Half-Life; D006801:Humans; D007191:Indazoles / Q000493:pharmacokinetics / Q000627:therapeutic use*; D008297:Male; D008875:Middle Aged; D010865:Pilot Projects; D011720:Pyrazoles / Q000627:therapeutic use*; D014839:Vomiting / Q000139:chemically induced / Q000517:prevention & control*
chemical_list: D000970:Antineoplastic Agents; D017829:Granisetron; D007191:Indazoles; D011720:Pyrazoles