Assessment of the steady-state pharmacokinetic interaction between etravirine administered as two different formulations and tenofovir disoproxil fumarate in healthy volunteers

Objective

Two open‐label, randomized, cross‐over trials in healthy volunteers were conducted to investigate the pharmacokinetic interaction between etravirine and tenofovir disoproxil fumarate.

Methods

Etravirine was administered as either 800 mg twice a day (bid) (phase II formulation in Study 1) or 200 mg bid (phase III formulation in Study 2) for 8 days followed by a 12 h pharmacokinetic evaluation. After a minimum of 14 days washout, tenofovir disoproxil fumarate 300 mg once a day was administered for 16 days. Volunteers were randomized to receive co‐administration of etravirine with tenofovir disoproxil fumarate on either days 1–8 or days 9–16 followed by a 12 h pharmacokinetic evaluation for etravirine on day 8 or 16, respectively. Plasma and urine tenofovir concentrations were determined on days 8 and 16 over 24 h.

Results

The least square mean (LSM) ratio [90% confidence interval (CI)] for the area under the plasma concentration–time curve from 0 to 12 h (AUC_{12 h}) for etravirine co‐administered with tenofovir disoproxil fumarate vs. etravirine alone was 0.69 (0.61–0.79) and 0.81 (0.75–0.88) in Studies 1 and 2, respectively. The LSM ratio (90% CI) for the effect of etravirine on tenofovir AUC_{24 h} was 1.16 (1.09–1.23) in Study 1 and 1.15 (1.09–1.21) in Study 2.

Conclusions

These alterations are not considered clinically relevant for either drug and no dose adjustment is necessary when etravirine and tenofovir disoproxil fumarate are co‐administered.     

Protective effects of polydatin against CCl4-induced injury to primarily cultured rat hepatocytes

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Naphthalimido derivatives as antifolate thymidylate synthase inhibitors

A new series of N-(substituted)benzyl-1,8-naphthalimides 4, structurally related to the previously reported thymidylate synthase (TS) inhibitor naphthaleins 3, were synthesized and compounds tested for their inhibition of several species of TS. Moreover, their in vitro cytotoxicity together with antimycotic and antibacterial properties were assayed. While no activity was detected in the antibacterial tests, the m-nitro (4ae) and the p-nitro (4af) derivatives were found able to partially inhibit TS at low micromolar concentrations. Introduction of nitro or (substituted)-amino groups in position 4 of the naphthalic ring always led to less active compounds.     

What do we know about how to do audit and feedback? Pitfalls in applying evidence from a systematic review

Background  

Improving the quality of health care requires a range of evidence-based activities. Audit and feedback is commonly used as a quality improvement tool in the UK National Health Service [NHS]. We set out to assess whether current guidance and systematic review evidence can sufficiently inform practical decisions about how to use audit and feedback to improve quality of care.     

Prevalence of Dental Fluorosis Among Primary School Children in Rural Areas of Chidambaram Taluk, Cuddalore District, Tamil Nadu, India

Background:

Fluorosis is one of the common but major emerging areas of research in the tropics. It is considered endemic in 17 states of India. However, the Cuddalore district of Tamil Nadu is categorised as a fluorosis non-endemic area. But clinical cases of dental fluorosis were reported in the field practice area of Department of Community Medicine, Rajah Muthiah Medical College, Annamalai University, Chidambaram. Since dental fluorosis has been described as a biomarker of exposure to fluoride, we assessed the prevalence and severity of dental fluorosis among primary school children in the service area.

Materials and Methods:

Children studying in six primary schools of six villages in the field practice area of Rural Health Centre of Faculty of Medicine, Annamalai University, Chidambaram, were surveyed. Every child was clinically examined at the school by calibrated examiners with Dean''s fluorosis index recommended by WHO (1997). Chi-square test, Chi-square trend test and Spearman''s rank correlation coefficient test were used for statistical analysis.

Results:

Five hundred and twenty-five 5- to 12-year-old school children (255 boys and 270 girls) were surveyed. The overall dental fluorosis prevalence was found to be 31.4% in our study sample. Dental fluorosis increased with age P < 0.001, whereas gender difference was not statistically significant. Aesthetically objectionable dental fluorosis was found in 2.1% of the sample. Villages Senjicherry, Keezhaperambai and Kanagarapattu revealed a community fluorosis index (CFI) score of 0.43, 0.54 and 0.54 with 5.6%, 4.8% and 1.4% of objectionable dental fluorosis, respectively. Correlation between water fluoride content and CFI values in four villages was noted to be positively significant.

Conclusion:

Three out of six villages studied were in ‘borderline’ public health significance (CFI score 0.4-0.6). A well-designed epidemiological investigation can be undertaken to evaluate the risk factors associated with the condition in the study region.