Piecing together human adult comparative pharmacokinetic trials and rodent studies: What happens to drug clearance in obesity?

In many comparative trials examining the effects of adult obesity on pharmacokinetics of drugs, conclusions were made based on values that were either not adjusted to total body weight or adjusted to non-obese body mass (e.g., ideal or lean body weight). In many cases these values were higher in the obese subjects. We have reviewed the data from comparative human trials, and it is apparent that in examining clearance normalization to total body weight (as typically done in studies involving pediatric obese patients), the clearances are often reduced in the obese. We have also reviewed the results of experimental obese versus non-obese rodent models. Those studies have mostly found that the systemic exposures to the same dose per body weight are increased, with obesity-related decreases in clearance. Furthermore, the expression of a number of important drug metabolizing enzymes are reduced in the experimental obese state. There is also evidence that obesity causes increases in the measured mass of eliminating organs such as liver and kidney. Human clearance normalized to total body weight appears to better reflect the underlying changes reported in the expression of protein and functional activity of drug clearance mechanisms.

Prevalence of periodontitis in obese patients in Bahrain: a cross-sectional study

Background Adult obesity has been associated with various systemic diseases and is an increasing problem in Bahrain. Recent evidence indicates a correlation between adult obesity and periodontitis. Hence the aim of this study was to assess the prevalence of periodontitis in overweight/obese adults in Bahrain and to determine the factors associated with periodontitis in these obese adults. Method This cross-sectional study was conducted in overweight subjects attending Ministry of Health (MOH) Nutrition Clinics at primary health centers in Bahrain. After obtaining the institutional ethics approval, the demographic and anthropometric data, including Body Mass Index (BMI) and waist circumference (WC) using World Health Organization (WHO) thresholds for severity of obesity, were recorded. Periodontal status was measured using the Community Periodontal Index (CPI) and the extent and severity of periodontal disease were categorized according to the number of sextants with CPI codes 3 and 4. Results A total of 372 participated with a mean age 44.0 (± 10.5) years for males, and 42.5 (± 11.2) years for females. Periodontitis was present in 361 (97%) of participants. Hypertension and diabetes were the most prevalent co-morbidities at 23.4% and 16% respectively. Mean WC was significantly greater in males at 114 cm (± 15.6) compared to females 109.5 cm (± 12.5) (p < 0.001). BMI was not associated with severity or extent of periodontitis but WC was weakly correlated in males but not in females (Spearman rho = + 0.2, p < 0.05). In the logistic regression model using overall WC to predict the severity of periodontitis, the adjusted OR was 1.02 (95% CI 1.00–1.04) and for age it was 1.05 (95% CI 1.00–1.07). Conclusion The prevalence of periodontitis was high in this sample of overweight Bahrainis. BMI was not correlated with periodontitis but WC had a weak positive correlation. Implementation of periodontal health screening as a routine part of a nutrition clinic program is recommended.