Subject(s)
Computational Biology/methods , Drug Interactions , Computer Simulation , Humans , Models, Theoretical , Pharmacokinetics , SoftwareABSTRACT
Typically, pharmacokinetic-pharmacodynamic (PK/PD) models use plasma concentration as the input that drives the PD model. However, interindividual variability in uptake transporter activity can lead to variable drug concentrations in plasma without discernible impact on the effect site organ concentration. A physiologically based PK/PD model for rosuvastatin was developed that linked the predicted liver concentration to the PD response model. The model was then applied to predict the effect of genotype-dependent uptake by the organic anion-transporting polypeptide 1B1 (OATP1B1) transporter on the pharmacological response. The area under the plasma concentration-time curve (AUC0-∞) was increased by 63 and 111% for the c.521TC and c.521CC genotypes vs. the c.521TT genotype, while the PD response remained relatively unchanged (3.1 and 5.8% reduction). Using local concentration at the effect site to drive the PD response enabled us to explain the observed disconnect between the effect of the OATP1B1 c521T>C polymorphism on rosuvastatin plasma concentration and the cholesterol synthesis response.
ABSTRACT
We report 2 cases of ureteral stump calculi presenting years after nephrectomy. Stones in the ureteral stump are extremely uncommon, and their occurrence has led us to review the possible mechanisms underlying their etiology.
Subject(s)
Nephrectomy/adverse effects , Ureteral Calculi/etiology , Aged , Female , Humans , Male , Middle AgedSubject(s)
Appendicitis/surgery , Hernia, Femoral/surgery , Intestinal Perforation/surgery , Aged , Aged, 80 and over , Appendectomy , Female , Humans , Middle Aged , Rupture, SpontaneousABSTRACT
A case of sigmoid carcinoma in a 16-year-old boy is presented and the topic of colonic carcinoma in the young is reviewed. Although colon carcinoma in the younger patient is uncommon, its prognosis is distinctly worse than in the adult population, because the preponderance of mucinous adenocarcinoma in children and young adults represents a more virulent type of colonic malignancy and because the delay in diagnosis contributes to a more advanced stage of the disease at the time of presentation. When dealing with symptoms potentially referrable to this disease, a thorough diagnostic work-up should ensue.
