Comparison of CYP3A activity between populations is complicated by frequency distribution differences in the regulatory CYP3A4*1B polymorphism and lower hepatic CYP3A activity associated with the variant allele. However, this reduction is modest; therefore no major and clinically important difference in CYP3A activity is present between Americans of African or European descent.

Opioids have a wide spectrum of P-glycoprotein activity, acting as both substrates and inhibitors, which might contribute to their varying central nervous system-related effects.

CPRDClinical Practice Research Datalink IRR Incidence rate ratio YPR Yearly prevalence ratio AIM The aim of this study was to describe the incidence of morbidities and the prevalence of medical prescriptions in a large Down syndrome population.METHOD A retrospective cohort study was carried out using the UK Clinical Practice ResearchDatalink from 1 January 2004 to 31 December 2013. We matched individuals with Down syndrome to randomly selected control participants by practice site, sex, birth year, and recording period.RESULTS A total of 6430 individuals with Down syndrome (3009 females, 3421 males) and 19 176 controls (8966 females, 10 210 males) were included in the study. The incidence of cardiovascular disorders, gastrointestinal diseases (incidence rate ratio [IRR] 7.9 at 3 to <6y: yearly prevalence ratio [YPR] for laxatives 4.7), and sleeping disorders (IRR 4.8 in 3 to <6y) was increased in children with Down syndrome versus control participants. New onset of congenital heart malformation, ear diseases, eye disorders, autism, hypothyroidism, diabetes, and obesity were more frequent in childhood and remained elevated in adulthood (overall IRR 35.5, 1.7, 3.1, 4.4, 13.1, 1.3, and 2.6 respectively), whereas the gap widened in adulthood for epilepsy and intellectual disability (IRR 15.2 and 158 respectively, in participants older than 30y). At ≥30 years, the incidence of hypotension and dementia was raised (IRR 3.0 and 92.1 respectively; YPR for dementia drugs: 76.3); and that of hypertension, depression and anxiety was lowered (IRR 0.2, 0.5, and 0.4 respectively). INTERPRETATIONThe profile of newly occurring morbidities in Down syndrome varies across the developmental lifespan.