Marcia Brackbill

Frequency of CYP3A4, CYP3A5, CYP2C9, and CYP2C19 variant alleles in patients receiving clopidogrel that experience repeat acute coronary syndrome

The presence of cytochrome P450 (CYP) variant alleles may reduce the activation of the prodrug clopidogrel to its active state. This research evaluated the frequency of variant alleles in the genes coding for CYP3A4, CYP3A5, CYP2C9, and CYP2C19 enzymes in patients on clopidogrel therapy and experiencing repeat acute coronary syndrome (ACS) compared to a control group with a matching ethnic composition. Real-time polymerase chain reaction was used for allelic discrimination. Complete data were obtained for 92 patients enrolled over a 3-month period. There were no significant differences in the presence of the examined CYP3A4, CYP3A5, CYP2C9, or CYP2C19 variant alleles between the two groups. The present data indicate that patients currently receiving clopidogrel therapy who present with repeat ACS do not have higher frequency of the examined variant alleles compared to a control group.

Prospective Trial of a Novel Nomogram to Achieve Updated Vancomycin Trough Concentrations

Purpose. To determine if the use of a novel vancomycin nomogram predicts dosing regimens that achieve target trough concentrations equal to or more accurate than dosing regimens calculated using traditional pharmacokinetic calculations, evaluate the incidence of subtherapeutic and supratherapeutic troughs, and assess pharmacists impressions of the nomogram. Methods. Prospective, open-label study in 473 patients who had a new order for vancomycin and were >18 years of age and ≤120 kg. Patients were randomized to the active group, dosed using the nomogram, or to the control group, dosed using traditional pharmacokinetic calculations already in place at our institution. Results. Patients dosed via nomogram were within the appropriate trough range in 44% of cases compared to 33% in the control group (P = 0.014). Vancomycin troughs less than 10 mcg/mL were significantly decreased with the use of nomogram (P = 0.032). Incidence of supratherapeutic troughs, greater than 20 mcg/mL, was not significantly different between groups (P = 0.706), and pharmacists agreed that the nomogram was easy to use and saved their time. Conclusions. A novel vancomycin nomogram was prospectively validated and found to be more effective than traditional pharmacokinetic dosing. The nomogram is being implemented as the standard dosing protocol at our institution.

Adjunctive Sitagliptin Therapy in Postoperative Cardiac Surgery Patients: A Pilot Study

Aim. We aimed to determine if sitagliptin added to standard postoperative standardized sliding-scale insulin regimens improved blood glucose. Methods. A prospective, randomized, double-blind, placebo-controlled pilot study was conducted in diabetic cardiac surgery patients. Patients received sitagliptin or placebo after surgery for 4 days. The primary endpoint was to estimate the effect of adjunctive sitagliptin versus placebo on overall mean blood glucose in the 4-day period after surgery. Results. Sixty-two patients participated. Repeated measures tests indicated no significant difference between the groups in the overall mean blood glucose level with a mean of 147.2 ± 4.8 mg/dL and 153.0 ± 4.6 mg/dL for the test and the control group, respectively (P = 0.388). Conclusions. Sitagliptin added to normal postoperative glucose management practices did not improve overall mean blood glucose control in diabetic patients in the postoperative setting.

Evaluation of the first international normalized ratio after acute care discharge to the primary care environment

Purpose To determine the percentage of patients who maintain a therapeutic INR (international normalized ratio) when presenting for their first INR follow-up in the primary care setting after hospital discharge. Methods Prospective observational trial enrolling patients newly initiated on warfarin. Results Data for 35 patients were collected. Fifty-one percent of patients were therapeutic at their first follow-up lab visit with 23% subtherapeutic and 26% supratherapeutic. Conclusion A low percentage of patients were therapeutic and more intervention is necessary in the immediate post-discharge time.