Publications

We have observed in clinical practice that Native Americans require lower dosages of tacrolimus to attain similar target blood trough levels compared to whites after renal transplant. Because there are no pharmacokinetic studies of tacrolimus in this ethnic group, we investigated whether this clinical observation could be corroborated by pharmacokinetic differences between Native Americans and other ethnic and racial groups. We recruited 24 adult Native American kidney transplant recipients on stable oral doses of tacrolimus for at least 1 month posttransplant. We conducted a 12-h steady-state pharmacokinetic profile for all of the patients and estimated pharmacokinetic parameters using NONMEM. The concentration-time data were fit to a linear two compartment model with first-order absorption and lag time using an empirical Bayesian approach. The mean estimate of oral clearance (CL/F) was 11.1 l/h. Compared with previously reported data in other ethnic and racial groups, the Native American cohort has approximately one third the clearance of other groups. Our pharmacokinetic study reveals the clinically observed low dose of tacrolimus in Native American renal transplant patients is associated with a decreased oral tacrolimus clearance. There is scant information available on the genetic or environmental characteristics unique to this ethnic group that affect pharmacokinetics compared to other, better-studied groups, and elucidation of these factors will provide information to further facilitate individualized drug treatment for tacrolimus and a wide range of other drugs with similar clearance processes.

In the United States and globally, increasing numbers of older parents are living with their adult children. Making the decision to live together requires careful thought and planning; particularly when the decision means the children will be responsible for their elder parents' care, the physicians of all parties should be consulted. More than one-third of caregivers state that they seek advice from their physician or other clinician when information is needed about this transition. Using the case of a couple receiving care from their daughter in her own home, we review the prevalence and epidemiology of adult children caring for a parent in the adult child's home, important issues to consider, and a framework for clinicians to help guide their patients through this transition. We describe the physician's ongoing role in caring for and advising both the older parent and the adult children during common stages of multigenerational living: before the move and during coresidency and subsequent care transitions.

Despite the increased risk of myocardial infarction, aortic dissection, and arrhythmias in patients with hypertension who use cocaine, the hemodynamic and arrhythmogenic effects of cocaine use have not been well characterized in this population. The authors hypothesized that patients with hypertension demonstrate extreme, transient changes in arterial pressures as well as new arrhythmic activity during cocaine use. Ambulatory blood pressures, heart rates, and electrocardiograms (AECGs) were recorded for 48 hours in 10 patients with a history of hypertension who smoke cocaine. Active cocaine use was identified through patient diaries and manual activation of the blood pressure cuff. Of the 10 patients studied (6 men, 7 African Americans, age 49±8 years), 8 were taking antihypertensive medications. The mean blood pressure prior to cocaine use was 126/77 mm Hg and average increase in systolic, diastolic, and mean arterial pressure after use was 74 mm Hg, 30 mm Hg, and 45 mm Hg, respectively (P<.0001 for all). There was no significant change in heart rate. AECGs demonstrated arrhythmic activity during cocaine use, including 6 patients with increased atrial and ventricular ectopy, 2 patients with episodes of nonsustained atrial tachycardia, and 1 patient with 3 episodes of nonsustained monomorphic ventricular tachycardia. Cocaine use resulted in extreme elevations in arterial pressures in patients with hypertension taking medication. Cocaine use was also associated with an increase in arrhythmic activity. These findings may underlie the heightened risk of myocardial infarction, aortic dissection, and potentially lethal arrhythmias in patients with hypertension who use cocaine.