Late-occurring and Long-circulating Metabolites of GABA Receptor Modulator AZD7325 Involving Metabolic Cyclization and Aromatization: Relevance to MIST Analysis and Application for Patient Compliance.

AZD7325 [4-amino-8-(2-fluoro-6-methoxyphenyl)--propylcinnoline-3-carboxamide] is a selective GABA receptor modulator intended for the treatment of anxiety disorders through oral administration. An interesting metabolic cyclization and aromatization pathway led to the tricyclic core of M9, i.e.

An open-label, non-randomised, phase 1, single-dose study to assess the pharmacokinetics of ceftaroline in patients with end-stage renal disease requiring intermittent haemodialysis.

For patients with normal renal function, the recommended ceftaroline fosamil dose is a 600 mg 1-h intravenous (i.v.) infusion every 12 h (q12h).

Evaluation of the pharmacokinetics and safety of single and multiple ceftaroline fosamil infusions in healthy Chinese and Western subjects.

Objectives: Two phase I studies in healthy Chinese (NCT01458743) and Western (NCT01612507) subjects evaluated the pharmacokinetics (PK) and safety of single and multiple ceftaroline fosamil 600 mg infusions administered every 8 or 12 hours (q8h or q12h).

Methods: Each study enrolled subjects sequentially into 1 of 2 cohorts (cohort 1: 60-minute infusions; cohort 2: 120-minute infusions). All subjects in the Chinese (n = 26) study received open label ceftaroline fosamil; in the Western study, subjects (n = 41) in each cohort were randomized 3 : 1 to ceftaroline fosamil or placebo infusions.

Safety, local tolerability and pharmacokinetics of ceftaroline fosamil administered in a reduced infusion volume.

Aims: The standard dose of ceftaroline fosamil for patients with normal renal function is 600 mg diluted in 250 ml by 60 min intravenous infusion every 12 h. This two part phase I trial (NCT01577589) assessed safety and local tolerability of multiple ceftaroline fosamil 50 ml and 250 ml infusions, and pharmacokinetics following single administrations of each infusion volume.

Methods: Part A was a placebo-controlled, double-blind, multiple dose crossover study.

A clinical study to assess CYP1A2 and CYP3A4 induction by AZD7325, a selective GABA(A) receptor modulator - an in vitro and in vivo comparison.

What Is Already Known About This Subject: • AZD7325 is an orally administered, potent, selective gamma-amino-butyric acid (GABA(A) ) α2,3 receptor modulator intended for the treatment of anxiety. • The induction effects of AZD7325 on CYP1A2 and CYP3A4 have not been systematically studied.

What This Study Adds: • The in vitro studies showed that AZD7325 was a moderate CYP1A2 inducer and potent CYP3A4 inducer.