An equilibrium model of TMDD is developed that recapitulates the essential features of the full general model and eliminates the need for estimating drug-binding microconstants that are often difficult or impossible to identify from typical in vivo pharmacokinetic data.

OBJECTIVETo determine the prevalence of subnormal testosterone concentrations in patients with obesity and with type 2 diabetes in a primary care clinic population.RESEARCH DESIGN AND METHODSFree testosterone concentrations of 1,849 men (1,451 nondiabetic and 398 diabetic) in the Hypogonadism In Males (HIM) study were analyzed. The HIM study was a U.S.-based cross-sectional study designed to define the prevalence of hypogonadism in men aged >45 years. Free testosterone was measured by equilibrium dialysis.RESULTSThe prevalence of subnormal free testosterone concentrations in lean, overweight, and obese nondiabetic men was 26% (n = 275), 29% (n = 687), and 40% (n = 489), respectively (P < 0.001 for trend), and 44% (n = 36), 44% (n = 135), and 50% (n = 227), respectively, in diabetic men (P = 0.46 for trend within group and P < 0.05 compared with nondiabetic men). The mean free testosterone concentration of diabetic men was significantly lower than that of nondiabetic men. Free testosterone concentrations were negatively and significantly (P < 0.001) related to age (r = −0.37), BMI (r = −0.18), and sex hormone–binding globulin (r = −0.11) in multiple regression analysis. The average decline of free testosterone concentrations was 7.8 pg/ml per decade in nondiabetic men and 8.4 pg/ml per decade in diabetic men.CONCLUSIONSForty percent of obese nondiabetic men and 50% of obese diabetic men aged ≥45 years have subnormal free testosterone concentrations. In view of its high prevalence, obesity is probably the condition most frequently associated with subnormal free testosterone concentrations in males. The concomitant presence of diabetes is associated with an additional increase in the prevalence of subnormal free testosterone concentrations.

This article is available online at http://dmd.aspetjournals.org ABSTRACT:Pharmacodynamics is the study of the time course of pharmacological effects of drugs. The field of pharmacodynamic modeling has made many advances, due in part to the relatively recent development of basic and extended mechanism-based models. The purpose of this article is to describe the classic as well as contemporary approaches, with an emphasis on pertinent equations and salient model features. In addition, current methods of integrating various system complexities into these models are discussed. Future pharmacodynamic models will most likely reflect an assembly of the basic components outlined in this review.

Background The Drug Burden Index (DBI), a measure of exposure to anticholinergic and sedative medications, has been independently associated with physical and cognitive function in a cross-sectional analysis of community dwelling older persons participating in the Health, Aging and Body Composition (Health ABC) study. Here we evaluate the association between DBI and functional outcomes in Health ABC participants over five years. Methods DBI was calculated at years 1 (baseline), 3 and 5 and a measure of the area under the curve for DBI (AUCDB) over the whole study period was devised and calculated. Physical performance was measured using the short physical performance battery (SPPB), usual gait speed, and grip strength. The association of DBI at each time point and AUCDB with year 6 function was analyzed in data from participants with longitudinal functional measures, controlling for socio-demographics, co-morbidities and baseline function. Results Higher DBI at years 1, 3 and 5 was consistently associated with poorer function at year 6. On multivariate analysis, a one unit increase in AUCDB predicted decreases in SPPB score of 0.08 (p = 0.01), gait speed of 0.01 m/s (p=0.004), and grip strength of 0.27 kg (p=0.004) at year 6. Conclusion Increasing exposure to medication with anticholinergic and sedative effects, measured with DBI, is associated with lower objective physical function over five years in community dwelling older people.