Pharmacokinetics and safety of aztreonam/avibactam for the treatment of complicated intra-abdominal infections in hospitalized adults: results from the REJUVENATE study.

Objectives: To investigate pharmacokinetics (PK) and safety (primary objectives) and efficacy (secondary objective) of the investigational monobactam/β-lactamase inhibitor combination aztreonam/avibactam in patients with complicated intra-abdominal infection (cIAI).

Methods: This Phase 2a open-label, multicentre study (NCT02655419; EudraCT 2015-002726-39) enrolled adults with cIAI into sequential cohorts for 5-14 days treatment. Cohort 1 patients received an aztreonam/avibactam loading dose of 500/137 mg (30 min infusion), followed by maintenance doses of 1500/410 mg (3 h infusions) q6h; Cohort 2 received 500/167 mg (30 min infusion), followed by 1500/500 mg (3 h infusions) q6h.

Drinking Ethanol Has Few Acute Effects on CYP2C9, CYP2C19, NAT2, and P-Glycoprotein Activities but Somewhat Inhibits CYP1A2, CYP2D6, and Intestinal CYP3A: So What?

We quantified the effect of acute ethanol exposure (initial blood concentrations 0.7 g/L) on major drug metabolizing enzymes and p-glycoprotein. Sixteen healthy Caucasians participated in a randomized crossover study with repeated administration of either vodka or water.

Pharmacokinetics and pharmacogenetics of capecitabine and its metabolites following replicate administration of two 500 mg tablet formulations.

Purpose: To describe concentration versus time profiles of capecitabine and its metabolites 5'-DFUR, 5'-DFCR and 5-FU, depending on tablet formulation and on frequent and/or relevant genetic polymorphisms of cytidine deaminase, dihydropyrimidine dehydrogenase, thymidylate synthase and methylenetetrahydrofolate reductase (MTHFR).

Methods: In 46 cancer patients on chronic capecitabine treatment, who voluntarily participated in the study, individual therapeutic doses were replaced on four consecutive mornings by the study medication. The appropriate number of 500 mg test (T) or reference (R) capecitabine tablets was given in randomly allocated sequences TRTR or RTRT (replicate design).

Population pharmacokinetic analysis of circadian rhythms in hepatic CYP3A activity using midazolam.

Diurnal changes in the activity of drug metabolizing enzymes may contribute to the variability in drug disposition and drug effects. The aim of this study was to quantify the circadian rhythmicity exhibited by hepatic CYP3A. A 10 μg/kg intravenous bolus dose, followed by a 30-hour 4 μg/kg/h intravenous infusion of midazolam, used as a probe substrate for hepatic CYP3A activity, was administered to 16 healthy volunteers (8 males and 8 females).

Pharmacokinetics, pharmacodynamics, and comparative bioavailability of single, oral 2-mg doses of dexamethasone liquid and tablet formulations: a randomized, controlled, crossover study in healthy adult volunteers.

Background: Dexamethasone is a glucocorticoid used widely worldwide for immunosuppressive treatment, allergies, bronchiolitis, and croup, among others. For children, liquid formulations are especially suitable because, compared with other dosage forms, both exact dosing and proper intake are facilitated.

Objective: The objective was to evaluate the pharmacokinetics, pharmacodynamics, and comparative bioavailability of a commercial liquid oral dexamethasone formulation intended for pediatric use relative to those of a tablet.

Absorption, pharmacokinetics, and safety of triclosan after dermal administration.

We evaluated the pharmacokinetics and safety of the antimicrobial agent triclosan after dermal application of a 2% triclosan-containing cream to six volunteers. Percutaneous absorption calculated from urinary excretion was 5.9% +/- 2.

Influence of posture on pharmacokinetics.

Introduction: Body position may influence physiological characteristics, such as perfusion, gastrointestinal function and plasma volume. These characteristics may interact with key factors determining the pharmacokinetics of drugs (dissolution, absorption, distribution, metabolism, excretion).

Objectives: Based on a systematic literature search, current data on the effect of posture on physiological characteristics and/or pharmacokinetics are summarized, and the relevance of possible effects, such as those presenting in clinical practice and clinical pharmacokinetic studies, is assessed.

HPLC analysis of the antifungal agent posaconazole in patients with haematological diseases.

Posaconazole is a new antifungal drug used in prophylaxis and therapy of fungal infections in patients with immunodeficiency. In the clinical development, posaconazole exhibits variable oral bioavailability. Hence drug monitoring is recommended.