A Safety Analysis of Programmed Death 1 Pathway Inhibitors in Patients With Solid Tumor Malignancies and Preexisting Autoimmune Disease.

OBJECTIVE: The aim of this study was to characterize the safety of programmed death 1 inhibitors in patients with preexisting autoimmune disease. METHODS: A medical records review study was conducted on adults with solid tumor malignancies who received ≥1 dose of pembrolizumab or nivolumab at Emory Healthcare from September 4, 2014 until December 31, 2019. All autoimmune patients were included (n = 77), whereas the nonautoimmune patients were randomized and the first 156 patients were included in a 2:1 ratio to autoimmune patients. The primary objective was the comparison of incidence of immune-related adverse events (irAEs) between patients with preexisting autoimmune disease and those without. Secondary objectives included irAE characterization, irAE treatment, and survival analyses. RESULTS: Preexisting autoimmune disease was controlled in all of the autoimmune patients before immunotherapy initiation. The rate of irAE was 32.7% in the nonautoimmune group and 42.9% in the autoimmune group (odds ratio, 0.65; 95% confidence interval, 0.37-1.14; p = 0.130). In the patient population diagnosed with a rheumatologic autoimmune disease, 23.81% of irAEs were considered to be a flare of their preexisting autoimmune disease. Less patients in the autoimmune group experienced a grade ≥3 irAE (21.21% vs 37.25%, p = 0.379) and received systemic corticosteroids (54.55% vs 67.35%, p = 0.241) for the treatment of the irAE. CONCLUSIONS: These results suggest that pembrolizumab and nivolumab can be safely administered in patients with controlled preexisting autoimmune diseases without a significant increase in irAE compared with patients without autoimmune diseases. Inclusion of patients with preexisting autoimmune diseases in prospective clinical trials is warranted.

Factors Associated With Clopidogrel Adherence in Community-Dwelling Patients.

OBJECTIVE: The purpose of this study was to characterize predictors of adherence to clopidogrel therapy focusing on patients' perceptions of clopidogrel and nuisance bleeding. METHODS: This was a cross-sectional study of community-dwelling cardiovascular patients with a self-reported prescription for clopidogrel. Self-report questionnaires assessed depressive symptoms, social support, nuisance bleeding, perceptions of clopidogrel, and adherence to therapy. Low, moderate, and high adherence groups based on the Morisky Medication Adherence Scale were compared and hierarchical multiple linear regression analysis was used to predict adherence. RESULTS: A total of 102 subjects were enrolled, and 55%, 28%, and 16% were classified as having low, moderate, and high adherence, respectively. Greater perceptions of clopidogrel necessity, lower perception of clopidogrel concern, and increased severity of nuisance bleeding were predictors of better adherence. CONCLUSIONS: Data from this cross-sectional study suggest that concerns about clopidogrel and feelings about its necessity play an important role in clopidogrel adherence.

Impact of a Geriatric Pharmacy Elective on Student Knowledge, Attitudes, and Empathy Regarding Older Adults.

OBJECTIVE: To evaluate the impact of a Geriatric Pharmacy elective on pharmacy students' knowledge, attitudes, and empathy regarding older adults. METHODS: Enrolled students in a 15-week Geriatric Pharmacy elective during 3 consecutive academic years were invited to complete a precourse and postcourse survey. The survey consisted of the revised Palmore facts on aging quiz, the University of California at Los Angeles geriatric attitudes scale, the Kiersma-Chen empathy scale, and demographic questions. The presurvey and postsurvey data were compared and the impact of demographic factors on student knowledge, attitudes, and empathy was assessed in an exploratory analysis. RESULTS: Sixty-six students participated in the study. Scores on the revised Palmore facts on aging quiz and the University of California at Los Angeles geriatric attitudes scale increased significantly postsurvey compared with presurvey. Student scores on the Kiersma-Chen empathy scale increased on the postsurvey compared with the presurvey, but this increase was not statistically significant. Student self-reported experience with older adults, race, and the course year impacted student performance. CONCLUSION: A geriatric elective positively impacted the students' knowledge and attitudes toward older adults. Future research should include validity and reliability testing of geriatric assessment scales in a diverse student population to ensure effective assessment of student knowledge, attitudes, and empathy in this patient population.

Implementation of self-care scenario simulations in a skills-based first year doctor of pharmacy course for student application of the Pharmacists' Patient Care Process.

BACKGROUND AND PURPOSE: The objective of this project was to assess the impact of self-care scenario simulations on first year doctor of pharmacy student performance and self-perceived confidence in applying the Pharmacists' Patient Care Process (PPCP) during self-care encounters. EDUCATIONAL ACTIVITY AND SETTINGS: Self-care scenarios were developed and used during low fidelity simulations in laboratory sessions in a skills-based course. Students met individually with faculty facilitators role-playing patients to apply the PPCP in four simulations. Facilitators graded student performance; a comparison was made between performance on the first and fourth simulation. Students completed a pre- and post-course survey regarding their self-perceived confidence in performance and knowledge in applying the PPCP in self-care encounters. FINDINGS: One hundred and eight (100%) of enrolled students voluntarily agreed to participate in this IRB-approved study. The median percentage of student scores on the fourth simulation, 90.7%, was higher compared to the median percentage of student scores on the first simulation, 82.4%, P < 0.001 with a raw difference of 8.3 percentage points, for participants with scores for both simulations, 106 (98%). For the self-perceived PPCP confidence survey, 100 (92.5%) participants completed both pre- and post-course surveys. Self-perceived confidence on 12 of the 15 survey items where students ranked their confidence in performance and knowledge in self-care encounters increased post- versus pre-course. SUMMARY: Simulations served as a useful tool in improving student performance in applying the PPCP in self-care encounters in a first year doctor of pharmacy course. Student self-perceived confidence in performance and knowledge in self-care encounters also increased.

Lack of a pharmacokinetic drug-drug interaction with venlafaxine extended-release/indinavir and desvenlafaxine extended-release/indinavir.

PURPOSE: To assess the effects of venlafaxine extended-release (XR) capsules and desvenlafaxine extended-release (XR) tablets upon indinavir pharmacokinetic properties when co-administrated to healthy volunteers. METHODS: This was an open-label, two-period, fixed-dose study conducted at the clinical research unit located on a university campus. Twenty-four healthy volunteers enrolled in the study (mean age 28.3 ± 8.0 years). Each subject received a single dose of indinavir 800 mg on day 1. Subsequently, subjects were then randomly assigned to either the venlafaxine XR group (N = 12) or the desvenlafaxine XR group (N = 12). Starting on day 2, venlafaxine XR was dosed at 37.5 mg/day for 4 days and increased to 75 mg/day for 6 days. Desvenlafaxine XR was dosed at 50 mg/day for 10 days. On day 12, indivanvir 800 mg was co-administered to both the venlafaxine XR and the desvenlafaxine XR groups. The pharmacokinetics of indinavir were determined both before and at the end of antidepressant dosing. Plasma indinavir, venlafaxine, and desvenlafaxine concentrations were assayed by high-performance liquid chromatography with ultra-violet (UV) detection. Indinavir pharmacokinetic parameters were calculated by noncompartmental analysis using validated computer software. RESULTS: Venlafaxine XR and desvenlafaxine XR did not produce any significant changes in indinavir disposition. Both antidepressants were well tolerated by the subjects with only minor adverse side effects. CONCLUSIONS: No pharmacokinetic drug-drug interaction was demonstrated between venlafaxine XR and indinavir or between desvenlafaxine XR and indinvair. The lack of interaction could be due to the venlafaxine and desvenlafaxine extended-release formulation.

Development of a script concordance test to assess clinical reasoning in a pharmacy curriculum.

INTRODUCTION: Clinical reasoning is a vital skill for student pharmacists in the provision of patient-centered care, but these skills are often difficult to assess in the didactic curriculum. A script concordance test (SCT) is an innovative assessment method that can be used to assess clinical reasoning skills. The objective of this study was to develop and refine an SCT to assess clinical reasoning skills of third year student pharmacists (P3s). METHODS: An SCT was written and administered to P3s. Pharmacy practice faculty members served as the expert group. The SCT was scored and Rasch analysis was performed. RESULTS: The SCT included 20 case vignettes and 60 questions. Test reliability was 0.34 with mean square values for all items between 0.7 and 1.3. Forty-two questions had a difficulty score between 0 and - 1 logits, indicating there were multiple questions with similar difficulty levels. Two case vignettes and 43.3% of questions (n = 26) were revised to enhance clarity and decrease ambiguity. CONCLUSIONS: The SCT is a tool to assess clinical reasoning in the didactic curriculum. Faculty can create the SCT and use statistical methods such as Rasch analysis to assess validity and reliability of the SCT.

Pharmacogenomics of warfarin dose requirements in Hispanics.

While Hispanics are the largest and most rapidly growing minority population in the United States, they are underrepresented in pharmacogenomic studies with warfarin. We sought to determine the combination of clinical and genetic influences of warfarin dose requirements in Hispanics. In addition, we tested the performance of published warfarin dosing algorithms derived from largely non-Hispanic cohorts in an inner-city U.S. Hispanic population. Genetic samples and clinical data were obtained from 50 Hispanics on a stable dose of warfarin. The contribution of cytochrome P450 2C9 (CYP2C9) and vitamin K epoxide reductase complex-1 (VKORC1) genotypes and clinical factors to warfarin dose requirements was determined. The correlation between the predicted dose using published algorithms and therapeutic dose was also assessed. Compared to the VKORC1-1639 GG genotype, warfarin dose requirements were 30% and 62% lower with the GA and AA genotypes, respectively (p=0.001). The combination of the VKORC1-1639G>A and CYP2C9 genotypes and clinical factors explained 56% of the inter-patient variability in warfarin dose. Warfarin dose predicted using algorithms derived from mostly non-Hispanic cohorts was significantly correlated with the therapeutic dose in our Hispanic cohort (r(2)=0.43 to 0.49; p<0.001); the predicted dose was within 1.0 mg/day of the therapeutic dose for 40% to 50% of patients. Our data suggest that factors influencing warfarin dose requirements in Hispanic Caucasians are similar to those previously described in European Caucasians and that dosing algorithms derived from non-Hispanic Caucasian cohorts are applicable to Hispanics living in the U.S.

Genetic testing for early detection of individuals at risk of coronary heart disease and monitoring response to therapy: challenges and promises.

Coronary heart disease (CHD) often presents suddenly with little warning. Traditional risk factors are inadequate to identify the asymptomatic high-risk individuals. Early identification of patients with subclinical coronary artery disease using noninvasive imaging modalities would allow the early adoption of aggressive preventative interventions. Currently, it is impractical to screen the entire population with noninvasive coronary imaging tools. The use of relatively simple and inexpensive genetic markers of increased CHD risk can identify a population subgroup in which benefit of atherosclerotic imaging modalities would be increased despite nominal cost and radiation exposure. Additionally, genetic markers are fixed and need only be measured once in a patient's lifetime, can help guide therapy selection, and may be of utility in family counseling.

Regulatory polymorphism in vitamin K epoxide reductase complex subunit 1 (VKORC1) affects gene expression and warfarin dose requirement.

Warfarin dose requirements have been associated with 2 main haplotypes in VKORC1, but the responsible polymorphisms remain unknown. To search for regulatory polymorphisms, we measured allelic mRNA expression of VKORC1 in human liver, heart, and B lymphocytes. The observed 2-fold allelic mRNA expression imbalance narrowed possible candidate SNPs to -1639G>A and 1173CA, and the tightly linked intron1 SNP 1173C>T, predict warfarin dose more accurately than intron 2 SNP 1542G>C in blacks. Increased warfarin dose requirement in blacks was accounted for by lower frequency of the -1639 A allele. Therefore, -1639G>A is a suitable biomarker for warfarin dosing across ethnic populations.

Evaluating Practice Readiness of Advanced Pharmacy Practice Experience Students Using the Core Entrustable Professional Activities.

Objective. To evaluate levels of entrustability and practice readiness in advanced pharmacy practice experience (APPE) students using a pilot instrument designed to assess their competency in performing the entrustable professional activities (EPAs) expected of new pharmacy graduates. Methods. A pilot instrument was developed directly from EPAs to measure entrustability levels on a scale of one to five. Five APPE preceptors from several different practice areas participated. Fourth-year students used the instrument to self-evaluate their knowledge and skills at the beginning, midpoint, and end of the APPE. The preceptors evaluated students using the same instrument at APPE midpoint and end. The instrument had assigned weights for each EPA and entrustability level for a score of 100 if all items were marked five. If a rating of non-applicable was chosen, score adjustments were made. All students in the graduating class of 2018 were invited to perform a self-evaluation at the end of the fourth (APPE) year using the same instrument that study participants used. Results. Twenty-eight students and five preceptors completed evaluations during the APPE year. Overall scores from both preceptor evaluations of students and student self-evaluations increased significantly from pre-APPE to midpoint to final. Student self-evaluations were only slightly higher than preceptor evaluations. The mean (SD) preceptor scores for students and student self-assessment scores at the end of each APPE were 85.4% (7.1) and 87.2% (10.3), respectfully. One practice manager EPA and three population health EPAs were considered to not be applicable by preceptors on ≥50% of evaluations. Approximately 94% of all graduating students completed the year-end self-evaluations, with a mean (SD) score of 89% (8.6) and no EPAs marked as not applicable. Conclusion. Pharmacy students' proficiency in EPA improved during individual APPEs. According to preceptors, students' greatest improvement in entrustability was in educating patients and colleagues regarding appropriate use of medications and collecting information to identify medication-related problems.

Influence of cyclooxygenase-1 genotype on ex vivo aspirin response in patients at risk for stroke.

BACKGROUND: We sought to determine whether cyclooxygenase-1 (PTGS1) genotype is associated with the ability of aspirin to inhibit platelet aggregation in patients at risk for stroke. METHODS: Blood and urine samples were collected from 60 subjects, including 28 African Americans, who were taking aspirin for primary or secondary stroke prevention. Samples were analyzed for the PTGS1 A-707G, PTGS1 P17L, and glycoprotein IIIa (ITGB3)P1(A1/A2) genotypes, ex-vivo platelet aggregation, serum cholesterol, plasma salicylate levels, and urinary 11-dehydrothromboxane B(2) (11-dhTxB(2)) concentrations. The association between PTGS1 A-707G and P17L genotypes and aspirin response, as assessed by ex vivo studies and 11-dhTxB(2) concentrations, was evaluated by statistical testing and nonlinear mapping. RESULTS: Salicylate concentrations, ITGB3 genotype distribution and 11-dhTxB(2) concentrations were similar among PTGS1 genotype groups. More subjects with the PTGS1 17PP versus PL genotype had incomplete ex-vivo inhibition of platelet aggregation by aspirin (57 vs. 20%; p = 0.04). Fifty-nine percent of subjects homozygous for both the PTGS -707A and 17P alleles, but none with both the PTGS1 -707G and 17L alleles had incomplete inhibition with aspirin; p = 0.04. Similarly, nonlinear mapping showed a direct relationship between the PTGS1 17P allele and decreased aspirin response. When analyzed separately by ethnicity, the association with the P17L genotype and aspirin response persisted in African Americans, but not Caucasians. CONCLUSIONS: Our data suggest that the PTGS1 P17L genotype contributes to response to aspirin as assessed by ex-vivo platelet aggregation. Our data further suggest that the association between PTGS1 genotype and aspirin response might vary by ethnicity.

Predictors of unstable anticoagulation in African Americans.

OBJECTIVE: We sought to identify contributors to unstable anticoagulation in African Americans. PATIENTS AND METHODS: Sixty African Americans on warfarin were enrolled. Cytochrome P450 2C9 and vitamin K epoxide reductase genotypes and vitamin K intake were assessed, and clinical and dietary data during the 12 months prior to enrollment were collected. Data were compared between stable and unstable patients, classified based on the proportion of international normalized ratio (INR) values outside the therapeutic range. RESULTS: The median proportion of out-of-range INRs among study participants was 44%; 28 patients had a higher proportion of INRs out-of-range and were included in the unstable group, with the remaining constituting the stable group. The median (IQR) number of clinic visits/year was higher among unstable versus stable patients [18 (15-22) vs. 16 (13-19); P = 0.03]. Higher warfarin doses, lower adherence, vomiting or diarrhea, and use of antiinfective agents were more common among unstable patients. Genotype was not associated with anticoagulation stability. After regression analysis, only poor adherence and gastrointestinal illness remained predictive of unstable anticoagulation. In a control group of Caucasians of similar age and sex distribution, poor adherence, but not gastrointestinal illness, was associated with unstable anticoagulation. CONCLUSION: We conclude that poor warfarin adherence and gastrointestinal illness are major contributors to unstable anticoagulation in African Americans. Our data suggest that, similar to Caucasians, improving warfarin adherence rates may be an important mean to improve anticoagulation control in African Americans. In addition, close monitoring during acute illness may be particularly important in this population.

CETP genotype and concentrations of HDL and lipoprotein subclasses in African-American men.

Aim: To assess the association between the CETP Taq1B and I405V polymorphisms with levels of lipoprotein subclasses in African-American (AA) men with and without Type 2 diabetes (T2DM). Patients & methods: AA men, over 30 years of age, with (n = 54) or without T2DM (n = 50), and not receiving lipid-lowering agents, underwent advanced lipid analysis and genotyping. Results & conclusion: In the total patient population Taq1B B2-allele carriers had significantly higher levels of large HDL subclasses (HDL-2b [p = 0.017] and HDL-L [p = 0.019]), lower levels of small-HDL subclasses (HDL-3a [p = 0.004] and HDL-3b [p = 0.031]), and lower levels of LDL subclasses (LDL-IVa [p = 0.012] and LDL-IIIb [p = 0.009]). The only significant genotype-diabetes interaction occurred with the HDL-2a subclass (p = 0.015). No statistically significant associations were seen with I405V genotype. Our observations of lower levels of small-HDL and higher levels of large-HDL suggest that a potentially important HDL subclass-CETP relationship exists.

A qualitative study of nuisance bleeding and medication-related beliefs with dual antiplatelet drug therapy.

OBJECTIVES: The purpose of this qualitative study was to explore perceptions of nuisance bleeding and medication-related beliefs among adults taking dual antiplatelet drug therapy. METHODS: We conducted qualitative telephone interviews with 34 community-dwelling adults with cardiovascular disease. RESULTS: Using qualitative content analysis, we identified 4 dominant themes: nuisance bruising, nuisance bleeding, importance of medication adherence, and duration of therapy. Participants' bruising was frequently more severe than expected given the force of the bump that caused it. Concerns focused on whether increased bleeding tendencies would lead to hemorrhage in the event of a major traumatic injury, confusion about the duration of therapy, and the rationale for when and why therapy should be discontinued. CONCLUSION: Excessive bruising and medication-related concerns about hemorrhage and duration of treatment were salient issues for participants. Effective clinician-patient communication should be used to assist individuals in managing concerns to help assure positive health outcomes with antiplatelet drugs.

A compliance assessment of midpoint formative assessments completed by APPE preceptors.

INTRODUCTION: Experiential pharmacy preceptors should provide formative and summative feedback during a learning experience. Preceptors are required to provide colleges and schools of pharmacy with assessments or evaluations of students' performance. Students and experiential programs value on-time completion of midpoint evaluations by preceptors. The objective of this study was to determine the number of on-time electronically documented formative midpoint evaluations completed by preceptors during advanced pharmacy practice experiences (APPEs). METHODS: Compliance rates of on-time electronically documented formative midpoint evaluations were reviewed by the Office of Experiential Education of a five-member consortium during the two-year study period prior to the adoption of Standards 2016. Pearson chi-square test and generalized linear models were used to determine if statistically significant differences were present. RESULTS: Average midpoint compliance rates for the two-year research period were 40.7% and 41% respectively. No statistical significance was noted comparing compliance rates for year one versus year two. However, statistical significance was present when comparing compliance rates between schools during year two. Feedback from students and preceptors pointed to the need for brief formal midpoint evaluations that require minimal time to complete, user friendly experiential management software, and methods for documenting verbal feedback through student self-reflection. CONCLUSIONS: Additional education and training to both affiliate and faculty preceptors on the importance of written formative feedback at midpoint is critical to remaining in compliance with Standards 2016.

Association of beta-blocker dose with serum procollagen concentrations and cardiac response to spironolactone in patients with heart failure.

STUDY OBJECTIVE: To determine whether beta-blocker dose influences cardiac collagen turnover and the effects of spironolactone on cardiac collagen turnover in patients with heart failure. DESIGN: Prospective clinical study. SETTING: Two heart failure centers. PATIENTS: Eighty-eight spironolactone-naïve patients with heart failure who were taking beta-blockers. INTERVENTION: In a subset of 29 patients, spironolactone was started at 12.5 mg/day, with the dosage titrated to 25 mg/day if tolerated. MEASUREMENTS AND MAIN RESULTS: Venous blood samples were collected from each patient. Serum procollagen type I and type III aminoterminal peptides (PINP and PIIINP) were determined by radioimmunoassay and compared between the 25 patients receiving low doses (< 50% of recommended target dose) and the 63 patients receiving high doses (> or = 50% of recommended target dose) of beta-blockers. Patients receiving low-dose beta-blockers had higher mean +/- SD PIIINP concentrations (6.6 +/- 3.5 vs 4.9 +/- 2.6 microg/L, p=0.03) and tended to have higher PINP concentrations (74.0 +/- 44.1 vs 57.1 +/- 28.6 microg/L, p=0.10) compared with those receiving high doses. A repeat blood sample was collected from the 29 patients who received spironolactone after 6 months of therapy. Changes in procollagen peptides also were compared in this subset between low-dose (9 patients) and high-dose (20 patients) beta-blocker groups. Low beta-blocker doses were associated with greater reductions in concentrations of PINP (median [intraquartile range] -14.3 microg/L [-9.8 to -19.3 microg/L] vs -2.5 microg/L [5.9 to -9.8 microg/L], p=0.02) and PIIINP (-1.4 microg/L [-0.9 to -2.4 microg/L] vs 0.1 microg/L [0.9 to -1.3 microg/L], p=0.045) with spironolactone therapy than high beta-blocker doses. In addition, 100% of the patients in this subset taking low-dose beta-blockers versus only 35% taking higher doses had reductions in both markers of cardiac fibrosis. CONCLUSION: Spironolactone may benefit patients with heart failure who cannot tolerate upward titration of beta-blocker dosages, at least in terms of its effects on cardiac remodeling.

Markers of cardiac collagen turnover are similar in patients with mild and more severe symptoms of heart failure.

Cardiac fibrosis plays an important role in the pathophysiology of heart failure. The authors sought to determine whether biomarkers of cardiac fibrosis for milder clinical degrees of heart failure are comparable to those of more advanced disease. Procollagen types I and III amino-terminal peptides (PINP and PIIINP) and type I collagen telopeptide (ICTP) were compared between aldosterone-antagonistnaive patients with heart failure and New York Heart Association class I or II (n=22/23) and class III or IV (n=42/3) symptoms. Median (interquartile) range concentrations of PINP (63.3 [44.2-88.8] vs 48.6 [37.8-74.9] microg/L), ICTP (7.0 [5.4-16.8] vs 6.5 [4.7-12.7] microg/L), and PIIINP (4.7 [3.2-7.0] vs 4.7 [2.9-7.3] microg/L) were comparable between patients with mild and moderate to severe disease, respectively. These data suggest that patients with mild heart failure may have similar degrees of cardiac fibrosis to patients with more severe disease and support the examination of antifibrotic therapy, including aldosterone antagonists, in milder degrees of heart failure.

Student pharmacists' preparedness to evaluate primary literature pre- and post-Advanced Pharmacy Practice Experiences.

BACKGROUND AND PURPOSE: The primary objective of this study was to assess the effect of formal primary literature evaluation (PLE) during advanced pharmacy practice experiences (APPEs) on student pharmacists' preparedness and knowledge related to literature evaluation. EDUCATIONAL ACTIVITY AND SETTING: A perception of preparedness survey and knowledge assessment was given to student pharmacists pre- and post-APPEs. Student pharmacists were also asked to characterize their opportunities for formal PLE during APPEs. Literature evaluation experiences, knowledge base and preparedness data were compared between student pharmacists who completed two or more PLE on APPE and those who did not. FINDINGS: A total of 211 student pharmacists completed 529 formal PLE during their APPE experiences. Quiz grades and average perception of preparedness increased significantly from pre- to post-APPE regardless of whether student pharmacists had the opportunity for formal PLE on APPE. Student pharmacists who completed two or more PLE on APPE stated they felt more confident in evaluating primary literature after APPE, had greater post-APPE preparedness scores and a trend towards higher post-APPE quiz scores. DISCUSSION AND CONCLUSION: APPEs provide an important opportunity for student pharmacists to improve their PLE knowledge.

Antibiotic drug interactions.

Drug-drug interactions in the field of infectious diseases continue to expand as new drugs are approved, metabolic enzymes and transporters are identified, and recommendations for co-administration of drugs are revised. This article provides an overview of the principles and mechanisms of drug-drug interactions and describes pharmacokinetic-pharmacodynamic interactions commonly associated with antibacterial therapy, antiviral agents (non-retroviral), and drugs for tuberculosis.

Racial differences in potassium response to spironolactone in heart failure.

Evidence of racial differences in aldosterone concentrations and K+ disposition suggests that response to aldosterone antagonism might vary by race. The authors sought to determine whether K+ response to spironolactone differs between African Americans and Caucasians with heart failure. Heart failure patients of African-American (n = 34) or Caucasian (n = 17) race were started on spironolactone 12.5 mg/d, with up-titration as tolerated. Laboratory values and drug therapy were similar between racial groups at baseline. Spironolactone was titrated to a median dose of 25 mg/d in both groups. Neither concomitant medications nor serum creatinine changed significantly in either group during spironolactone dose titration. Median serum K+ concentrations increased by 0.5 mEq/L (range, -0.7 to 1.6 mEq/L) in Caucasians, but only 0.1 mEq/L (range, -0.8 to 0.9 mEq/L) in African Americans; p < 0.01. These data suggest that African Americans with heart failure may be less responsive to the renal effects of spironolactone.