title: Pharmacokinetics and blister fluid penetration of brodimoprim in adults.
abstract: We investigated the pharmacokinetic properties of brodimoprim (B), a new diaminopyrimidine, including its penetration into suction blister fluid (SBF) after a single or multiple oral dose in 15 patients with a mean age of 61.5 +/- 9.3 yrs, suffering from respiratory tract infections with normal renal and hepatic function. Patients were divided into 3 groups of 5 cases each, according to treatment plan: Group I = B 400 mg single dose day 1; Group II = B 400 mg qD day 1 and 200 mg qD days 2 to 4; Group III = B 200 mg BID day 1 and 200 mg qD days 2 to 4. Concentrations were determined microbiologically using B. subtilis ATCC 6633 as the test organism with a lower limit of sensitivity of 0.37 mg/l. With a single oral dose of 400 mg (Group I) a computed serum Cmax of 2.9 +/- 0.6 mg/l was observed 5.6h after administration, with a elimination half-life (t1/2 beta) of 32.3 +/- 4.1 h. In SBF a mean peak of 1.9 +/- 0.6 mg/l was reached after 6h with a t1/2 beta of 34.7 +/- 5.4 h and a penetration index (Pl), obtained by the AUCSBF/AUCs percent ratio of 61%. With multiple doses serum peak concentrations increased significantly, while the time to reach the peak (Tmax) was shorter (3.7-4.2 h) than after a single dose. Main kinetic parameters, such as t1/2 beta, mean residence time (MRT), elimination rate constant (Kel) and AUC, were significantly higher in Group II and III patients than in Group I cases. Similar differences were observed among the main SBF kinetic parameters.(ABSTRACT TRUNCATED AT 250 WORDS)
authors.affiliation: Dip. Farmacologia, Università degli Studi di Firenze, Italy.
authors.forename: A
authors.initials: A
authors.lastname: Novelli
authors.forename: T
authors.initials: T
authors.lastname: Mazzei
authors.forename: E
authors.initials: E
authors.lastname: Meli
authors.forename: M I
authors.initials: MI
authors.lastname: Cassetta
authors.forename: S
authors.initials: S
authors.lastname: Fallani
authors.forename: P
authors.initials: P
authors.lastname: Periti
mesh_terms: D000328:Adult; D000368:Aged; D001768:Blister / Q000097:blood / Q000378:metabolism*; D005122:Exudates and Transudates / Q000378:metabolism*; D006801:Humans; D008297:Male; D008875:Middle Aged; D014295:Trimethoprim / Q000031:analogs & derivatives* / Q000097:blood / Q000493:pharmacokinetics
chemical_list: D014295:Trimethoprim; C037079:brodimoprim