Pharmacokinetics of dopamine in healthy male subjects

BACKGROUND: Dopamine is an agonist of alpha, beta, and dopaminergic receptors with varying hemodynamic effects depending on the dose of drug being administered. The purpose of this study was to measure plasma concentrations of dopamine in a homogeneous group of healthy male subjects to develop a pharmacokinetic model for the drug. Our hypothesis was that dopamine concentrations can be predicted from the infusion dose using a population-based pharmacokinetic model. METHODS: Nine healthy male volunteers aged 23 to 45 yr were studied in a clinical research facility within our academic medical center. After placement of venous and arterial catheters, dopamine was infused at 10 microg x kg(-1) x min(-1) for 10 min, followed by a 30-min washout period. Subsequently, dopamine was infused at 3 microg x kg(-1) x min(-1) for 90 min, followed by another 30-min washout period. Timed arterial blood samples were centrifuged, and the plasma was analyzed by high-performance liquid chromatography. Mixed-effects pharmacokinetic models using NONMEM software (NONMEM Project Group, University of California, San Francisco, CA) were used to determine the optimal compartmental pharmacokinetic model for dopamine. RESULTS: Plasma concentrations of dopamine varied from 12,300 to 201,500 ng/l after 10 min of dopamine infusion at 10 microg x kg(-1) x min(-1). Similarly, steady-state dopamine concentrations varied from 1,880 to 18,300 ng/l in these same subjects receiving 3-microg x kg(-1) x min(-1) infusions for 90 min. A two-compartment model adjusted for body weight was the best model based on the Schwartz-Bayesian criterion. CONCLUSIONS: Despite a homogeneous population of healthy male subjects and weight-based dosing, there was 10- to 75-fold intersubject variability in plasma dopamine concentrations, making standard pharmacokinetic modeling of less utility than for other drugs. The data suggest marked intraindividual and interindividual variability in dopamine distribution and/or metabolism. Thus, plasma dopamine concentrations in patients receiving dopamine infusion at identical rates may vary profoundly. Our data suggest that dosing dopamine based on body weight does not yield predictable blood concentrations.     

The association between body mass index and musculoskeletal foot disorders: a systematic review

The primary aim of this systematic review was to investigate the relationship between body mass index (BMI) and foot disorders. The secondary aim was to investigate whether weight loss is effective for reducing foot pain. Five electronic databases (Ovid MEDLINE, Ovid EMBASE, Ovid AMED, CINAHL and The Cochrane Library) and reference lists from relevant papers were searched in April 2011. Twenty‐five papers that reported on the association between BMI and musculoskeletal foot disorders met our inclusion criteria and were reviewed. The evidence indicates: (i) a strong association between increased BMI and non‐specific foot pain; and (ii) a strong association between increased BMI and chronic plantar heel pain in a non‐athletic population. The evidence is inconclusive regarding the relationship between BMI and the following specific disorders of the foot; hallux valgus, tendonitis, osteoarthritis and flat foot. With respect to our second aim, there were only two prospective cohort studies that reported a reduction in foot symptoms following weight loss surgery. In summary, increased BMI is strongly associated with non‐specific foot pain in the general population and chronic plantar heel pain in a non‐athletic population. However, there is currently limited evidence to support weight loss to reduce foot pain.