The importance of appropriate antimicrobial dosing: pharmacokinetic and pharmacodynamic considerations.

The increasing antimicrobial resistance of common respiratory pathogens has led to a reevaluation of the selection of antimicrobial dosing regimens in terms of their pharmacokinetic (PK) and pharmacodynamic (PD) properties. Pharmacokinetics, when considered as part of a specific dosing regimen, can help determine the time course of drug concentrations in the serum, tissues, body fluids, and at the site of infection. Pharmacodynamics provides surrogate markers for clinical and bacteriologic efficacy based on the relationships between the serum and tissue concentrations of selected antimicrobial agents relative to the mean inhibitory concentrations of causative bacteria over time.

Relationship between fluoroquinolone area under the curve: minimum inhibitory concentration ratio and the probability of eradication of the infecting pathogen, in patients with nosocomial pneumonia.

Our objective was to prospectively determine the factors influencing the probability of a good microbiological or clinical outcome in patients with nosocomial pneumonia treated with a fluoroquinolone. Levofloxacin was administered as an infusion of 500 mg/h for 1.5 h (total dose, 750 mg).

Pharmacokinetics and safety of GW433908 and ritonavir, with and without efavirenz, in healthy volunteers.

Objective: To evaluate the safety and pharmacokinetic interaction between GW433908, ritonavir (RTV), and efavirenz (EFV).

Methods: In period 1, subjects received either a once daily (QD) regimen of GW433908 1395 mg + RTV 200 mg (Study 1) or a twice daily (bid) regimen of GW433908 700 mg + RTV 100 mg (Study 2) for 14 days. In period 2, subjects received EFV 600 mg QD with either the same GW433908 + RTV regimen as in period 1 (arm 1) or with a GW433908 + RTV regimen that included an additional 100 mg of RTV (arm 2) for 14 days.

Pharmacodynamics and clinical use of anti-HIV drugs.

Antiretroviral drug exposure has been linked to both antiviral efficacy and the development of toxicity and further research in this area is ongoing and necessary. Use of these data may have important implications for TDM of HAART regimens in clinical practice. TDM, in conjunction with an assessment of the patient's viral resistance in the form of an IQ, needs to be examined and validated in large clinical trials.

Comparative pharmacokinetic analysis by standard two-stage method versus nonparametric population modeling.

Study Objective: To compare the two-stage method, a widely used analytical method in pharmacokinetic studies, with nonparametric population modeling by using the same data set for determining the oral bioavailability of ribavirin.

Design: Pharmacokinetic analysis. Clinical research center.

In vitro-in vivo model for evaluating the antiviral activity of amprenavir in combination with ritonavir administered at 600 and 100 milligrams, respectively, every 12 hours.

The study objective was to evaluate the pharmacodynamics of amprenavir in an in vitro system, develop an exposure target for maximal viral suppression, and determine the likelihood of target attainment based on the pharmacokinetics of amprenavir and ritonavir in human immunodeficiency virus (HIV)-infected patients. Population pharmacokinetic data were obtained from 13 HIV-infected patients receiving amprenavir and ritonavir in doses of 600 and 100 mg, respectively, every 12 h. A 2,500-subject Monte Carlo simulation was performed.

Optimal sampling schedule design for populations of patients.

Generation of pharmacodynamic relationships in the clinical arena requires estimation of pharmacokinetic parameter values for individual patients. When the target population is severely ill, the ability to obtain traditional intensive blood sampling schedules is curtailed. Population modeling guided by optimal sampling theory has provided robust estimates of individual patient pharmacokinetic parameter values.

Claiming our place: women with serious mental health issues and support groups for abused women.

Many women with serious mental health issues also deal with abuse and have difficulty accessing services. Despite the fact that groups have been found to be one of the most useful tools in healing from the effects of abuse, many professionals see women with serious mental health issues as unable to benefit from counselling and, in particular, from groups for abused women. This study indicates that, when mental health issues are addressed and the group structures and expectations are modified to allow women control over their participation, serious mental health issues are not a barrier to participation in groups.