Co-administration Of Proton Pump Inhibitors Research Articles

Retrospective evaluation of methotrexate elimination when co‐administered with proton pump inhibitors

The aim was to assess potential interaction between methotrexate (MTX) and proton pump inhibitors (PPIs) in patients receiving high-dose MTX. Records of 56 adults receiving 201 cycles of MTX were reviewed to determine effects of PPI administration on MTX elimination. Repeated-measures logistic regressions and Cox regressions were performed to evaluate the possible drug interaction. Despite a significant difference between those receiving a PPI and not receiving a PPI in median MTX levels at 24 (8.0 vs. 3.9 μmol l(-1) , respectively, P = 0.013) and 72 h after MTX administration (0.08 vs. 0.05 μmol l(-1) , respectively, P = 0.037), there was no difference between those receiving a PPI and not receiving a PPI in the proportion of patients experiencing delayed elimination at 24 (19.2% vs. 20.2%, respectively, P = 1.000) and 72 h (36.2% vs. 33.7%, respectively, P = 0.765). When data were analysed using Cox regression, controlling for multiple cycles of MTX per patient, PPI use was not a significant predictor of time to MTX < 0.1 μmol l(-1) . When the clustering effect of multiple cycles of MTX per patient was controlled for, co-administration of PPIs was not a significant predictor of MTX level (P = 0.969). A comparison of patients with delayed elimination at any time point and those without delayed elimination indicated that PPI use was not a significant predictor of delayed elimination (P = 0.607). This study does not support previous findings of a significant interaction between PPIs and MTX. Based on these results, the clinical significance of any potential interaction is likely to be small.

Effect of Esomeprazole With/Without Acetylsalicylic Acid, Omeprazole and Lansoprazole on Pharmacokinetics and Pharmacodynamics of Clopidogrel in Healthy Volunteers

The effect of proton pump inhibitors (PPIs) on the pharmacokinetics and pharmacodynamics of clopidogrel was assessed in two healthy volunteer crossover studies. Study 1: subjects received clopidogrel alone (300-mg loading dose, then 75 mg/day for 28 days) and two of three PPIs (omeprazole 80 mg, esomeprazole 40 mg or lansoprazole 60 mg) plus clopidogrel for 29 days in three treatment periods (randomized treatment sequence assignment). Study 2: subjects received clopidogrel alone (75 mg/day for 9 days) and clopidogrel alone for 4 days followed by clopidogrel plus fixed-combination esomeprazole 20 mg/low-dose acetylsalicylic acid (ASA) 81 mg for 5 days in two treatment periods (randomized treatment sequence assignment). Pharmacokinetic effects were estimated by measuring active metabolite of clopidogrel, and pharmacodynamic effects by inhibition of adenosine diphosphate (ADP)-induced platelet aggregation. There was a relative decrease of up to 50 % in exposure to the active metabolite of clopidogrel with the different PPIs (study 1), and close to 40 % with esomeprazole/low-dose ASA (study 2), compared with clopidogrel alone. There was an absolute decrease of up to 17 % in inhibition of ADP-induced platelet aggregation with co-administration of different PPIs, compared with clopidogrel alone; however, no differences in platelet inhibition were observed during co-administration with the esomeprazole/low-dose ASA fixed-dose combination. Omeprazole, esomeprazole and lansoprazole decreased systemic exposure to the active metabolite of clopidogrel in healthy volunteers, leading to modest decreases in its antiplatelet effect. However, no apparent differences in platelet inhibition were observed when esomeprazole was co-administered with low-dose ASA as a fixed-dose combination.

Factors influencing posaconazole plasmatic concentrations in patients presenting with acute myeloid leukemia

PurposeThe effectiveness of posaconazole (PSZ) prophylaxis on invasive fungal infections, in patients presenting with acute myeloid leukemia (AML), seems to be correlated to its blood plasma concentration. Our goal was to identify the risk factors for underdosing. Patients and methodsWe retrospectively reviewed the records of patients treated for AML treated with PSZ, during a 2-year period. Assays<500ng/mL were considered as under dosed. ResultsFifty-nine assays (43 patients) were performed during induction (n=22) or consolidation (n=37) chemotherapy. PSZ treatment was initiated within a median of 3 days before neutropenia with a first assay performed at 8 days (3–28). The median PSZ blood plasma concentration was 375ng/mL (<200–1900). Forty-one (69%) treatment were maintained until the end of neutropenia. One patient presented with candidemia, 9 with possible invasive aspergillosis, without any significant association with underdosing. The univariate analysis showed that co-administration of proton pump inhibitors (PPIs) (P=0.01) and cause of hospitalization (induction chemotherapy vs consolidation, P=0.008) were associated with underdosing, contrary to feeding difficulties (P=0.07) and digestive disorders (P=0.5). The multivariate analysis confirmed the impact of PPI use (P=0.01) and the cause of hospitalization (P=0.003). ConclusionThis study highlights the major impact of PPI administration on PSZ blood plasma levels and stresses the risk of non-effective prophylaxis during induction treatment of AML.

Pharmacokinetic Drug Interaction Profiles of Proton Pump Inhibitors: An Update

Proton pump inhibitors (PPIs) are used extensively for the treatment of gastric acid-related disorders, often over the long term, which raises the potential for clinically significant drug interactions in patients receiving concomitant medications. These drug–drug interactions have been previously reviewed. However, the current knowledge is likely to have advanced, so a thorough review of the literature published since 2006 was conducted. This identified new studies of drug interactions that are modulated by gastric pH. These studies showed the effect of a PPI-induced increase in intragastric pH on mycophenolate mofetil pharmacokinetics, which were characterised by a decrease in the maximum exposure and availability of mycophenolic acid, at least at early time points. Post-2006 data were also available outlining the altered pharmacokinetics of protease inhibitors with concomitant PPI exposure. New data for the more recently marketed dexlansoprazole suggest it has no impact on the pharmacokinetics of diazepam, phenytoin, theophylline and warfarin. The CYP2C19-mediated interaction that seems to exist between clopidogrel and omeprazole or esomeprazole has been shown to be clinically important in research published since the 2006 review; this effect is not seen as a class effect of PPIs. Finally, data suggest that coadministration of PPIs with methotrexate may affect methotrexate pharmacokinetics, although the mechanism of interaction is not well understood. As was shown in the previous review, individual PPIs differ in their propensities to interact with other drugs and the extent to which their interaction profiles have been defined. The interaction profiles of omeprazole and pantoprazole sodium (pantoprazole-Na) have been studied most extensively. Several studies have shown that omeprazole carries a considerable potential for drug interactions because of its high affinity for CYP2C19 and moderate affinity for CYP3A4. In contrast, pantoprazole-Na appears to have lower potential for interactions with other medications. Lansoprazole and rabeprazole also seem to have a weaker potential for interactions than omeprazole, although their interaction profiles, along with those of esomeprazole and dexlansoprazole, have been less extensively investigated. Only a few drug interactions involving PPIs are of clinical significance. Nonetheless, the potential for drug interactions should be considered when choosing a PPI to manage gastric acid-related disorders. This is particularly relevant for elderly patients taking multiple medications, or for those receiving a concomitant medication with a narrow therapeutic index.

METHOTREXATE AND PROTON PUMP INHIBITORS: ARE THERE ANY NEGATIVE PHARMACOLOGIAL EFFECTS?

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中等量メソトレキサート治療の血中濃度に及ぼすプロトンポンプ阻害薬，脱水，急性腎障害の影響

Recent studies have reported methotrexate (MTX) delayed excretion in the case of co-administration of proton pump inhibitor (PPI) in high-dose MTX therapy. We investigated whether PPI influenced the serum concentration of MTX (MTX-con) in intermediate-dose MTX chemotherapy. We also investigated the relation between MTX-con and blood urea nitrogen (BUN) / serum creatinine (SCr) ratio before the treatment, which is a kind of laboratory indicator of dehydration. MTX-con and SCr increase after the treatment. We examined MTX-con for 36 cycles in 19 candidates in our institution. Co-administration of PPI was observed in 8/36 (22%). Average MTX-con at 48 hr after MTX administration with and without co-administration of PPI was 0.32 ± 0.12 μM and 0.41 ± 0.37 μM respectively (P = 0.92). A BUN/SCr ratio indication over 20 before therapy was observed in 10/36 (28%). Average MTX-con at 48 hr after MTX administration was 0.21 ± 0.14 μM in the BUN/SCr ratio 20 and over group, 0.46 ± 0.36 μM in the BUN/SCr ratio under 20 group (P < 0.01). SCr increased over 0.3 mg/dL after MTX administration was observed in 4/36 (11%). Average MTX-con after 48 hr MTX administration was 0.72 ± 0.6 μM in the SCr 0.3 and over group, 0.35 ± 0.27 μM in the SCr under 0.3 mg/dL group (P < 0.05). Co-administration of PPI is not associated with MTX delayed excretion and BUN/SCr ratio before the treatment and SCr increase after the treatment was suggested as a possible factor in MTX-con influence.

The Proton Pump Inhibitor Lansoprazole, but not Rabeprazole, the Increased Blood Concentrations of Calcineurin Inhibitors in Japanese Patients with Connective Tissue Diseases

Proton pump inhibitors (PPIs) are frequently coadministered with calcineurin inhibitors (CNIs) such as tacrolimus (TAC) and cyclosporin A (CSA), to treat or prevent upper gastrointestinal complications in Japanese patients with connective tissue diseases (CTDs). The coadministration of PPIs increases the blood concentration of TAC due to drug interaction. We retrospectively investigated the influence of the coadministration of PPIs and CNIs, as well as the influence of the cytochrome P450 (CYP) 2C19 gene polymorphism status, on the blood concentrations of TAC and CSA in patients with CTDs. Patients treated with TAC (n=35) or CSA (n=30) were enrolled and divided into three groups according to the PPI they received: lansoprazole (LPZ)-combined, rabeprazole (RPZ)-combined, and non-PPI-combined groups. We compared the blood concentrations of TAC or CSA and the incidences of adverse events among the three groups. CYP2C19 gene polymorphisms were also assessed to investigate its influence on the blood concentration of TAC or CSA. LPZ significantly increased the blood concentration of TAC 12 hours after TAC administration (p=0.030 and p=0.003, respectively) and CSA (p=0.047 and p=0.014, respectively) in comparison with RPZ and non-PPI-combined treatment. There were no significant differences in the mean CSA blood concentration two hours after administration in patients with or without PPI treatment, in the incidence of adverse events, or in the CYP2C19 gene polymorphism status among the three groups. Combining agents that are mainly metabolized by CYP3A4 such as LPZ elevates the blood concentrations of TAC and CSA, which could leading to adverse events.

The effect of lansoprazole, an OCT inhibitor, on metformin pharmacokinetics in healthy subjects

Gastro-esophageal reflux disease is common in patients with type 2 diabetes. A common treatment is the co-administration of proton-pump inhibitors (PPIs) and metformin. To date, however, the effects of co-administration of PPIs, which inhibit organic cation transporter (OCT) activity, on the action of metformin (a well-known substrate of OCTs) have not been clearly demonstrated. This was a randomized, double-blind, two-way crossover, placebo-controlled trial. Healthy male volunteers (n = 20) received metformin (single dose 1,000 mg on day 1 and single dose 750 mg on day 2, with a 12-h interval) co-administered with placebo or with lansoprazole (30 mg). Plasma concentrations of metformin were measured up to 24 h after the second dose. The glucose-lowering effects of metformin were evaluated by the oral glucose tolerance test before and after each single dose of metformin within the 2-day period. Lansoprazole increased the mean metformin maximum plasma concentration and area under the plasma concentration-time curve from zero to 24 h after the second dosing by 15 and 17 %, respectively (P < 0.05). Moreover, lansoprazole prolonged the metformin elimination half-life from 3.9 to 4.5 h and decreased its renal clearance by 13 % (P < 0.05). However, lansoprazole had no effect on the maximum glucose level and the area under the serum glucose concentration-time curve of metformin. Collectively, we found a modest pharmacokinetic drug interaction between lansoprazole and metformin, which suggests that the concomitant use of these drugs should be appropriately monitored. Further studies are warranted to assess changes in metformin pharmacokinetics in patients with diabetes receiving long-term lansoprazole therapy.

Antifungal Prophylaxis with Posaconazole in Patients with Acute Myeloid Leukemia: Dose Intensification Coupled with Avoidance of Proton Pump Inhibitors Is Beneficial in Shortening Time to Effective Concentrations

This study aimed to assess the influence of dose frequency and the presence or absence of cotreatment with proton pump inhibitors (PPIs) on the time to a target trough concentration (Cmin) of >700 ng/ml with posaconazole in the first 8 days of antifungal prophylaxis in hematological patients. This was a retrospective, observational study performed with 42 adult patients with acute myeloid leukemia who underwent posaconazole prophylaxis with 200 mg every 8 h (q8h) or 200 mg q6h after receiving induction chemotherapy and who had at least three subsequent therapeutic drug monitoring assessments during the first 8 days of treatment. The cohort was split into four groups (group 1, 200 mg q8h without PPI; group 2, 200 mg q8h with PPI; group 3, 200 mg q6h without PPI; group 4, 200 mg q6h with PPI). Rapid attainment of the target Cmin was obtained only in group 3 (P < 0.01) (median Cmin on day 4 of 935.5 ng/ml [interquartile range, 760.0 to 1,270.0 ng/ml] in group 3, versus 567.0 ng/ml [346 to 906 ng/ml] in group 1, 420.0 ng/ml [326.2 to 527.2 ng/ml] in group 2, and 514.0 ng/ml [403.7 to 564.7 ng/ml] in group 4). A linear accumulation of posaconazole over time was observed among patients in groups 1 and 3, regardless of the total daily dosage, differently from what occurred among those receiving PPI cotreatment (groups 2 and 4). Dose intensification (200 mg q6h) coupled with avoidance of PPI coadministration may represent a very powerful strategy to rapidly achieve effective concentrations with posaconazole in neutropenic hematological patients.

Proton pump inhibitors and clopidogrel: an association to avoid?

Dual antiplatelet therapy with aspirin and clopidogrel reduces cardiovascular events following an acute coronary syndrome or stent implantation, but the associated increased risk of gastro-intestinal bleeding often leads to the co-administration of proton pump inhibitors (PPIs). PPIs have been shown to decrease antiplatelet effects of clopidogrel ex vivo, raising concerns about the cardiovascular safety of this drug combination. Clinical trials investigating PPI-clopidogrel interactions have provided conflicting results and are all subject to methodological critiques. The much desired and much needed prospective, double-bind, randomized, placebo-controlled trials with adequate follow-up and sample size have not yet been performed. Indeed, the Clopidogrel and the Optimization of GI Events Trial, which would have had such characteristics, was stopped prematurely. As a consequence, the question of the PPI-clopidogrel interaction is still unresolved, and clinical consequences cannot be excluded. At this time such combination therapy should, therefore, be provisionally advocated only for patients at high risk of bleeding (prior upper gastro-intestinal bleeding, advanced age, concomitant use of warfarin, steroidal or non-steroidal anti-inflammatory drugs and Helicobacter pylori infection) and avoiding PPIs with strong affinity for cytochrome CYP2C19, such as omeprazole and esomeprazole.

Mechanistic Understanding of the Effect of PPIs and Acidic Carbonated Beverages on the Oral Absorption of Itraconazole Based on Absorption Modeling with Appropriate in Vitro Data

Proton pump inhibitors (PPIs) are potent gastric acid suppressing agents and are among the most widely sold drugs in the world. However, even though these antisecretory agents are regarded as safe, they can alter the pharmacokinetics of coadministered drugs. Due to the suppression of gastric acid secretion, they can significantly alter the intragastric pH conditions and are thus likely to affect the bioavailability of coadministered drugs requiring an acidic gastric environment for dissolution and subsequent absorption. Among these drugs can be found itraconazole, a poorly soluble triazole-type antifungal compound. Based on observations reported in the literature, gastric pH alterations due to the coadministration of PPIs or acidic beverages can significantly decrease (PPI) or increase (e.g., Coca-Cola) the bioavailability of this compound. In the present work we estimated the fraction of itraconazole that can be absorbed (fabs) from Sporanox capsules or an itraconazole-HBenBCD complex formulation after oral administration with and without coadministration of a PPI or an acidic (carbonated) beverage. For this purpose, the sensitivity of the two formulations toward the impact of various gastric variations (pH, volume, and emptying rate) as they can result from such administration conditions was studied using solubility and dissolution experiments and a physiologically based absorption model. Simulating coadministration of the two formulations with a PPI resulted in a significant (∼ 10-fold) decrease in itraconazole fabs, indicating the pH to be essential for in vivo dissolution and subsequent absorption. The fabs of itraconazole after coadministration of an acidic beverage (Coca-Cola) was far lower than the fabs obtained for itraconazole alone and did not support the observations reported in the literature. These results clearly indicate that in contrast to PPIs, which seem to affect itraconazole bioavailability mainly via intragastric pH changes, coadministered Coca-Cola is likely to alter a range of gastrointestinal parameters relevant to in vivo dissolution rather than solely affecting the intragastric pH.

Pharmacodynamic effect of cilostazol versus clopidogrel in stented patients during proton pump inhibitor co-administration: the result of the ACCEL-PARAZOL study

Pharmacodynamic effect of cilostazol versus clopidogrel in stented patients during proton pump inhibitor co-administration: the result of the ACCEL-PARAZOL study

Impact of the proton pump inhibitors and CYP2C19*2 polymorphism on platelet response to clopidogrel as assessed by four platelet function assays

Previous studies suggested a possible negative interference of proton pump inhibitors (PPIs) on clopidogrel's antiplatelet effect because of the competitive inhibition of the CYP 2C19 isoenzyme. Moreover, carriers of the loss-of-function allele of CYP2C19 polymorphism (CYP2C19*2) display significantly lower responses to clopidogrel. In this study, we investigated the association between CYP2C19*2 genotype, PPI intake and clopidogrel resistance in patients with coronary artery disease (CAD) and their effect on clinical outcome. We recruited 95 patients with CAD receiving chronic clopidogrel therapy in combination with aspirin. Platelet reactivity was simultaneously assessed by INNOVANCE PFA-100 P2Y, ADP-induced light transmission aggregometry (LTA), flow-cytometric vasodilator-stimulated phosphoprotein (VASP)-phosphorylation assay and multiple electrode aggregometry (Multiplate). Cardiovascular outcomes were recorded during 1-year follow-up period. Only platelet reactivity assessed by measuring platelet phosphorylated-VASP demonstrated a significant higher platelet reactivity in carriers of CYP2C19*2 (p=0.023). The other methods displayed higher - but not statistically significant - platelet reactivity in patients carrying the CYP2C19*2 variant as compared with non-carriers. Patients on PPIs demonstrated almost similar suppression of platelet reactivity in comparison with those not treated with PPIs by all platelet function assays. In logistic regression analysis none of the platelet function assays measurements were related with clinical outcomes. Similarly neither CYP2C19*2 genetic variant nor PPI treatment were associated with adverse clinical events. PPI co-administration did not influence clopidogrel's antiplatelet effect on laboratory testing by all platelet function assays used. On the contrary, patients carrying CYP2C19*2 genotype had significantly higher residual platelet reactivity as estimated by VASP-phosphorylation assay.

Proton Pump Inhibitors and Potential Interactions with Clopidogrel: An Update

Clopidogrel, an antiplatelet agent, is increasingly prescribed for patients with recent stroke, myocardial infarction, acute coronary syndrome, and/or patients post-coronary stent insertion to prevent recurrent cardiovascular events. Since clopidogrel can increase the risk of gastrointestinal hemorrhage, co-administration of proton pump inhibitors (PPIs) has been recommended, particularly in patients at high risk. In 2009, the FDA issued warnings about potential interactions between clopidogrel and PPIs, given the fact that both drugs are metabolized via the cytochrome P450 pathway. Prior studies have demonstrated significant reduction in platelet inhibition when PPI therapy is administered to subjects on clopidogrel therapy. Two meta-analyses were published in 2010 and 2011, the first suggesting association of PPIs with adverse cardiovascular events when observational studies were examined, but noting that the results were limited by the presence of significant heterogeneity. The second meta-analysis did not find a significant increase in the risk of adverse primary events (which included all cause mortality, cardiovascular death, myocardial infarction, or stroke), and concluded that analysis of the data from two randomized controlled trials yielded a risk difference of zero. An updated literature search was performed to assess clinical studies describing interactions between PPIs and clopidogrel published from 2011-2012. The majority of these studies did not show significant interactions when primary cardiac outcomes were considered. More importantly, the newer data demonstrated that PPI usage independently was a risk factor for adverse CV outcomes, since most PPI users were older patients who were more likely to have concomitant co-morbid conditions. Two updated reviews also concluded that the presence of confounding factors likely explained differences in results between studies, and that there were no significant differences in effects on clopidogrel between individual proton pump inhibitors. Overall, clinicians can assure their patients that combination therapy is safe when indicated in a patient at high risk of GI bleeding, but they should also stop PPI therapy if it is not clinically indicated.

Tu1821 Beyond Acid Suppression: Novel Targets in Gastroesophageal Reflux Disease by Gene Microarray Profiling

elimination groups. Co-administration of PPI was more prevalent in delayed elimination group compared with normal elimination group (90% vs. 62%). No difference was found in NSAIDs or vancomycin co-administration between the groups. Multivariate logistic regression model adjusted for age and gender revealed that co-administration of PPI was an independent factor associated with delayed MTX elimination (OR 12.3, p=0.04). Conclusion: Co-administration of proton pump inhibitors delays elimination of plasma methotrexate in patients with high-dose methotrexate therapy.

Potential interaction between proton pump inhibitor and clopidogrel

Clopidogrel is an anti-platelet agent commonly used in patients with atherosclerotic cardiovascular (CV) disease. Although formerly considered safe, several studies reported that the use of clopidogrel may cause a significant increase in the rate of gastrointestinal (GI) bleeding. This adverse effect could be minimized by coadministration of proton pump inhibitor (PPI). However, since PPI and clopidogrel share the same metabolic pathway, it has been hypothesized that the administration of PPI following clopidogrel therapy may cause a reduction in its anti-platelet effect, thereby increasing the risk of CV events. Recent studies found no significant inhibition in the activation of clopidogrel by CYP2C19 with administration of PPI in vitro. Pharmacokinetic and pharmacodynamic studies, as well as clinical studies, reported conflicting results regarding the potential interaction between PPI and clopidogrel. Until now, the available study investigated the PPI-clopidogrel interaction are primarily observational. The COGENT study is the only prospective, placebo-controlled trial examined the PPI-clopidogrel interaction. This study revealed no significant increase in CV events in patients receiving PPI following clopidogrel therapy, compared to the control group. Though remains controversial, current expert consensus recommended the administration of PPI in patients receiving clopidogrel, particularly in high-risk patients. (Med J Indones. 2013;22:57-62) Keywords: Cardiovascular, clopidogrel, gastrointestinal, proton pump inhibitor

Proton pump inhibitors and clopidogrel: an association to avoid?

Dual antiplatelet therapy with aspirin and clopidogrel reduces cardiovascular events following an acute coronary syndrome or stent implantation, but the associated increased risk of gastrointestinal bleeding often leads clinicians to the co-administration of proton pump inhibitors (PPIs). PPIs have been shown to decrease antiplatelet effects of clopidogrel ex vivo, raising doubts on the safety of this drug combination. Clinical trials investigating PPI-clopidogrel interaction have provided conflicting results and have been often criticized. Moreover, a prospective, double-bind, randomized, placebo-controlled study conducted with adequate follow-up and sample size has not yet been performed. Indeed, the COGENT trial, which would have had such characteristics, has been stopped prematurely. The question is therefore still unresolved, and clinical effects of PPI-clopidogrel interaction cannot be excluded. As a practical consequence, this combination therapy is recommended only for patients at high risk of bleeding (prior upper gastrointestinal bleeding, advanced age, concomitant use of warfarin, steroidal or non-steroidal anti-inflammatory drugs and Helicobacter pylori infection), avoiding in any case PPIs with greater affinity for CYP2C19, such as omeprazole and esomeprazole.

The effects of risedronate administered in combination with a proton pump inhibitor for the treatment of osteoporosis

This study was performed to investigate the effects of the co-administration of proton pump inhibitor (PPI) on the efficacy of bisphosphonate (BP) treatment for osteoporosis. A total of 180 women with low bone mineral density were randomly divided into four groups, one in which sodium risedronate was administered with sodium rabeprazole and one in which only risedronate was administered (BP+PPI and BP groups, respectively). The biomarkers were measured at the baseline and every 3months, inlcuding: N-terminal telopeptide of type I collagen corrected for creatinine, bone-specific alkaline phosphatase (BAP), parathyroid hormone, bone mineral density (BMD) of the lumbar spine and physical parameters evaluated according to the SF-36v2™ Health Survey. Statistical comparisons of these parameters were performed after 9months. Data were available for a total of 137 patients (62 in the BP group and 75 in the BP+PPI group). The Δ% value of increase in BMD and improvement of physical functioning in the BP+PPI group were significantly larger, and its decrease in BAP in the BP+PPI group was significantly smaller than that in the BP group. It is expected that risedronate administration in combination with a PPI may be more effective not only for treating osteoporosis but also improving physical fitness than treatment with risedronate alone.

2012 American College of Clinical Pharmacology Annual Meeting September 23rd–25th San Diego, California

2012 American College of Clinical Pharmacology Annual Meeting September 23^rd–25^th San Diego, California

Clinical Significance of the Clopidogrel–Proton Pump Inhibitor Interaction After Peripheral Endovascular Intervention for Claudication

Despite numerous studies in the cardiology literature, the clinical impact of proton pump inhibitor (PPI) administration on the antiplatelet effect of clopidogrel remains controversial. The objective of this study is to evaluate the effects of concurrent PPI and clopidogrel administration on outcomes after percutaneous transluminal angioplasty and stenting (PTA&S) of the superficial femoral artery (SFA) for claudication. Retrospective review of a prospectively maintained database (2004-2010) identified patients undergoing PTA&S of the SFA for lifestyle-limiting claudication (Rutherford Class III). Statistical analysis included univariate comparison (Wilcoxon, chi-square) of demographics, lesion characteristics, complication rates, and outcome measures. Patency comparisons were made with Cox-PH multivariable models and Kaplan-Meier survival analysis. Totally, 109 limbs were treated in 103 patients. All were prescribed clopidogrel for 1 month; concurrent PPI use (+PPI) was identified after 42 (38.5%) interventions. There were no statistically significant differences in demographics, comorbidity prevalence, lesion length, degree of stenosis, or runoff associated with PPI use. There were no cases of early thrombosis in either group. There were more instances of patency loss (28 [50%] vs 21 [42%]; P = .40) in patients with +PPI, and a trend toward reduced primary patency that did not achieve statistical significance (P = .5). By multivariate analysis only TransAtlantic Inter-Society Consensus (TASC) D lesions were independent predictors of primary (hazards ratio [HR] = 4.366; [95% confidence interval (CI): 1.291-14.764; P = .018) and assisted patency loss (HR = 6.815 [1.181-39.327]; P = .032). The clinical significance of the clopidogrel-PPI interaction is a controversial topic that has been the subject of numerous studies in the cardiology literature. This is the first report to examine this medication interaction after peripheral intervention. While there is no apparent association between PPI coadministration with clopidogrel in this series, the high prevalence of PPI use among patients prescribed clopidogrel following peripheral intervention warrants ongoing attention to this purported medication interaction.