Definition, willingness-to-pay, and ranking of quality attributes of U.S. pork as defined by importers in Asia and Mexico.

A survey was conducted from November 2009 to April 2010 to determine how importers of pork define 7 predetermined quality categories (food safety, customer service, eating quality, product specification, packaging, visual characteristics, and production history) and to estimate willingness-to-pay (WTP) and establish best-worst (B/W) scaling (rank) for the 7 quality categories. Interviews were conducted in Hong Kong/China (n = 83), Japan (n = 48), Mexico (n = 70) and Russia (n = 54) with importers of U.S. pork or those who had purchased U.S. pork from distributors in the last 3 yr. Interviews used dynamic routing software and were structured such that economic factors for purchase were addressed first, allowing all responses to focus on quality. Questions about WTP and B/W were asked and then each respondent was asked to define what each quality category meant to them. Generalized linear mixed models were used to analyze frequency data. Over 70% of interviewees in Hong Kong/China, Japan, and Mexico responded that purchase price was influential in deciding whether or not to purchase imported pork. This number was lower in Russia, where respondents stated tariff rates were also important, indicating market access was a larger issue in Russia. Food safety was the most important quality category (price was not included as a part of quality) for imported pork followed by specifications. Respondents indicated some form of government inspection was how they defined food safety, whereas product size, weight, and subcutaneous fat were all included in the definition of specifications. Interviewees were more likely to pay premiums for customer service and less likely to pay premiums for packaging (P < 0.05). The premiums that were willing to be paid for guarantees of quality for imported pork variety meats were numerically lower than for whole muscle cuts or processed products. A guarantee associated with food safety of processed pork products was found to be the quality attribute for which importers would be willing to pay the highest premium. Production history was found to be the least important quality attribute for importers of all types of U.S. pork, except those in Japan. Exporters could increase profitability if a guarantee of customer service was made. Price, tariffs, and exchange rates are important to pork importers; these results indicated that if certain quality attributes could be guaranteed, exporters could increase profitability.

A consolidated biovigilance system for blood, tissue and organs: one size does not fit all.

Biovigilance systems to assess and analyze risks for disease transmission through the transfer of organs, tissue, cells and blood between people is part of administrative oversight and has impact upon clinical practice and policy. In 2009, a formal recommendation by the Public Health Service requested that Health and Human Services fund and support efforts to consolidate national biovigilance efforts. There are differences in the biovigilance issues involved in organ and tissue donation/transplantation. If disease avoidance is made the dominant principle guiding organ donor testing, an unintended consequence may be an increase in deaths on the waiting list. We propose that overall benefit for the organ transplant recipient, tempered by patient informed awareness of limited organ availability and assessment processes, should be the guiding principle of such a system.

Efficacy of performing Warner-Bratzler and slice shear force on the same beef steak following rapid cooking.

The ability to perform Warner-Bratzler and slice shear force on the same beef top loin steak was investigated. Three, 2.54-cm steaks from top loins (n=99) were allotted to either Warner-Bratzler only (WBS), slice shear force only (SSF), or Warner-Bratzler and slice shear force (WBS/SSF). Steaks were thawed at 2 degrees C for 48h prior to cooking. Steaks were cooked to 71 degrees C using a conveyor convection oven and allowed to cool at room temperature for a minimum of 4h. Steaks allotted to WBS used six 1.27-cm cores and steaks allotted for WBS/SSF used four cores. Steaks allotted to SSF and WBS/SSF used one, 1 cm x 5 cm slice. Correlations among WBS and SSF for all steaks ranged from 0.49 to 0.69 (P<0.0001). When correlations were generated for steak location within the top loin, the relationships among WBS and SSF performed in the same steak ranged from 0.53 to 0.70 (P<0.05). These results indicate that it may be feasible to conduct WBS and SSF on the same top loin steak, and that the steak taken 2.54 cm from the 13th rib is the optimal location for this combination of procedures.

Effect of visual marbling on sensory properties and quality traits of pork loin.

Pork loins (N=53) were selected from a commercial packing plant to determine the influence of subjective marbling score on sensory attributes and eating quality properties. The pork loins were obtained from commercially raised hybrid barrows (average carcass weight=67.7 kg), originating from nine cooperating herds, and fed similar diets throughout the finishing period. Carcass quality measurements, trained sensory panel analyses, fatty acid composition, thiobarbituric acid-reactive substance (TBARS) index, and cholesterol content were assessed and analyzed on the individual pork loins. With an increase in marbling level, there was a corresponding decrease in drip loss (P=0.049) and observed increases in pH (P=0.001), sensory tenderness (P=0.001), and sensory juiciness scores (P=0.017). The most notable results demonstrated that protein concentrations were reduced as marbling levels amplified (P=0.012). The increase in marbling score was observed to be a significant source of variation in polyunsaturated fatty acid (PUFA) concentrations. Linoleic and arachidonic acids decreased in both raw and cooked samples as marbling score increased. The data demonstrated that visual marbling score does have an influence on sensory properties and pork quality.

Establishing an appropriate mode of comparison for measuring the performance of marbling score output from video image analysis beef carcass grading systems.

A beef carcass instrument grading system that improves accuracy and consistency of marbling score (MS) evaluation would have the potential to advance value-based marketing efforts and reduce disparity in quality grading among USDA graders, shifts, and plants. The objectives of this study were to use output data from the Video Image Analysis-Computer Vision System (VIA-CVS, Research Management Systems Inc., Fort Collins, CO) to develop an appropriate method by which performance of video image analysis MS output could be evaluated for accuracy, precision, and repeatability for purposes of seeking official USDA approval for using an instrument in commerce to augment assessment of quality grade, and to use the developed standards to gain approval for VIA-CVS to assist USDA personnel in assigning official beef carcass MS. An initial MS output algorithm was developed (phase I) for the VIA-CVS before 2 separate preliminary instrument evaluation trials (phases II and III) were conducted. During phases II and III, a 3-member panel of USDA expert graders independently assigned MS to 1,068 and 1,242 stationary carcasses, respectively. Mean expert MS was calculated for each carcass. Additionally, a separate 3-member USDA expert panel developed a consensus MS for each carcass in phase III. In phase II, VIA-CVS stationary triple-placement and triple-trigger instrument repeatability values (n = 262 and 260, respectively), measured as the percentage of total variance explained by carcasses, were 99.9 and 99.8%, respectively. In phases II and III, 95% of carcasses were assigned expert MS for which differences between individual expert MS, and for which the consensus MS in phase III only, was < or = 96 MS units. Two differing approaches to simple regression analysis, as well as a separate method-comparability analysis that accommodates error in both dependent and independent variables, were used to assess accuracy and precision of instrument MS predictions vs. mean expert MS. Method-comparability analysis was more appropriate in assessing the bias and precision of instrument MS predictions. Ether-extractable fat percentages (n = 257; phase II) differed among MS (P < 0.05) but were not suitable to predict or validate assigned MS. The performance and reproducibility of expert MS assignment in future evaluations was considered, and an official USDA performance standard was established, to which an instrument must conform to be approved for official on-line MS assessment. The VIA-CVS subsequently was approved to assign MS to carcasses on-line after completion of a 2006 USDA instrument approval trial conducted according to methods developed during completion of this study.

KDIGO clinical practice guideline for the care of kidney transplant recipients: a summary

The 2009 Kidney Disease: Improving Global Outcomes (KDIGO) clinical practice guideline on the monitoring, management, and treatment of kidney transplant recipients is intended to assist the practitioner caring for adults and children after kidney transplantation. The guideline development process followed an evidence-based approach, and management recommendations are based on systematic reviews of relevant treatment trials. Critical appraisal of the quality of the evidence and the strength of recommendations followed the Grades of Recommendation Assessment, Development, and Evaluation (GRADE) approach. The guideline makes recommendations for immunosuppression and graft monitoring, as well as prevention and treatment of infection, cardiovascular disease, malignancy, and other complications that are common in kidney transplant recipients, including hematological and bone disorders. Limitations of the evidence, especially the lack of definitive clinical outcome trials, are discussed and suggestions are provided for future research. This summary includes a brief description of methodology and the complete guideline recommendations but does not include the rationale and references for each recommendation, which are published elsewhere.

Gefitinib treatment in hormone-resistant and hormone receptor-negative advanced breast cancer.

BACKGROUND: Acquired and de novo endocrine resistance in breast cancer (BC) may be associated with overexpression of epidermal growth factor receptor (EGFR). Gefinitib is an orally active selective EGFR inhibitor which might benefit advanced breast cancer (ABC) patients either with acquired hormone resistance or with hormone receptor (HR)-negative tumors. PATIENTS AND METHODS: A two-arm multicenter phase II trial of oral gefitinib 500 mg/day was planned in two groups of 45 patients with ABC for whom chemotherapy was not currently indicated. Group 1 had hormone-resistant BC defined as HR-positive BC with progression after treatment with tamoxifen and an aromatase inhibitor. Group 2 had HR-negative BC. Tumor response was assessed every 8 weeks. The primary end point was the clinical benefit rate (CBR). RESULTS: Forty patients with hormone-resistant BC had a CBR of 0%. Two of 25 HR-negative BC patients showed stable disease (less than a 50% reduction and less than a 25% increase in the sum of the products of two perpendicular diameters of all measured lesions and the appearance of no new lesions) at 24 weeks resulting in a CBR of 7.7% (95% CI 0.9% to 25.1%). Enrollment ceased due to the low CBR. Toxicity resulted in treatment interruption (46%), dose reduction (20%) and withdrawal (11%) of patients. CONCLUSION: At a dose of 500 mg/day, gefitinib monotherapy resulted in a low CBR and no tumor response was identified.

The effect of endocrine responsiveness on high-risk breast cancer treated with dose-intensive chemotherapy: results of International Breast Cancer Study Group Trial 15-95 after prolonged follow-up.

BACKGROUND: The role of adjuvant dose-intensive chemotherapy and its efficacy according to baseline features has not yet been established. PATIENTS AND METHODS: Three hundred and forty-four patients were randomized to receive seven courses of standard-dose chemotherapy (SD-CT) or three cycles of dose-intensive epirubicin and cyclophosphamide (epirubicin 200 mg/m(2) plus cyclophosphamide 4 mg/m(2) with filgrastim and progenitor cell support). All patients were assigned tamoxifen at the completion of chemotherapy. The primary end point was disease-free survival (DFS). This paper updates the results and explores patterns of recurrence according to predicting baseline features. RESULTS: At 8.3-years median follow-up, patients assigned DI-EC had a significantly better DFS compared with those assigned SD-CT [8-year DFS percent 47% and 37%, respectively, hazard ratio (HR) 0.76; 95% confidence interval 0.58-1.00; P = 0.05]. Only patients with estrogen receptor (ER)-positive disease benefited from the DI-EC (HR 0.61; 95% confidence interval 0.39, 0.95; P = 0.03). CONCLUSIONS: After prolonged follow-up, DI-EC significantly improved DFS, but the effect was observed only in patients with ER-positive disease, leading to the hypothesis that efficacy of DI-EC may relate to its endocrine effects. Further studies designed to confirm the importance of endocrine responsiveness in patients treated with dose-intensive chemotherapy are encouraged.

Quality of life and quality-adjusted survival (Q-TWiST) in patients receiving dose-intensive or standard dose chemotherapy for high-risk primary breast cancer.

Quality of life (QL) is an important consideration when comparing adjuvant therapies for early breast cancer, especially if they differ substantially in toxicity. We evaluated QL and Q-TWiST among patients randomised to adjuvant dose-intensive epirubicin and cyclophosphamide administered with filgrastim and progenitor cell support (DI-EC) or standard-dose anthracycline-based chemotherapy (SD-CT). We estimated the duration of chemotherapy toxicity (TOX), time without disease symptoms and toxicity (TWiST), and time following relapse (REL). Patients scored QL indicators. Mean durations for the three transition times were weighted with patient reported utilities to obtain mean Q-TWiST. Patients receiving DI-EC reported worse QL during TOX, especially treatment burden (month 3: P<0.01), but a faster recovery 3 months following chemotherapy than patients receiving SD-CT, for example, less coping effort (P<0.01). Average Q-TWiST was 1.8 months longer for patients receiving DI-EC (95% CI, -2.5 to 6.1). Q-TWiST favoured DI-EC for most values of utilities attached to TOX and REL. Despite greater initial toxicity, quality-adjusted survival was similar or better with dose-intensive treatment as compared to standard treatment. Thus, QL considerations should not be prohibitive if future intensive therapies show superior efficacy.

Antimalarial drug resistance and the importance of drug quality monitoring.

The availability of counterfeit and poor quality drugs contribute to resistance and erroneous efficacy study results as well as directly affecting the health of individuals. This report describes the importance of drug quality monitoring as part of a comprehensive disease surveillance program.

Fake antimalarials in Southeast Asia are a major impediment to malaria control: multinational cross-sectional survey on the prevalence of fake antimalarials.

OBJECTIVE: To assess the prevalence of counterfeit antimalarial drugs in Southeast (SE) Asia. DESIGN: Cross-sectional survey. SETTING: Pharmacies and shops selling antimalarial drugs in Myanmar (Burma), Lao PDR, Vietnam, Cambodia and Thailand. MAIN OUTCOME MEASURES: Proportion of artemisinin derivatives or mefloquine containing drugs of substandard quality. RESULTS: Of the 188 tablet packs purchased which were labelled as 'artesunate' 53% did not contain any artesunate. All counterfeit artesunate tablets were labelled as manufactured by 'Guilin Pharma', and refinements of the fake blisterpacks made them often hard to distinguish from their genuine counterparts. No other artemisinin derivatives were found to be counterfeited. Of the 44 mefloquine samples, 9% contained <10% of the expected amount of active ingredient. CONCLUSIONS: An alarmingly high proportion of antimalarial drugs bought in pharmacies and shops in mainland SE Asia are counterfeit, and the problem has increased significantly compared with our previous survey in 1999-2000. This is a serious threat to public health in the region.

In vitro and in vivo evaluation of albumin-encapsulated primaquine diphosphate prepared by nebulization into heated oil.

Nebulization of an aqueous mixture of primaquine diphosphate and albumin into heated vegetable oil produces spherical particles with an average size of 6 microm. The microparticles are relatively stabile in buffers of pH 7.2 and 4.5 and completely degrade when exposed to proteolytic enzymes such as trypsin. Pharmacokinetic evaluation of the albumin-encapsulated primaquine diphosphate shows significantly higher levels in mouse liver tissue relative to free drug 2-48 h post-IP administration. Higher AUC (2.8x), lower steady-state volume of distribution (10x) and slower half-life (2.5x) relative to an equivalent dose of free primaquine diphosphate suggest liver targeting and sustained release of the drug from the microparticles.

Five years managing metastatic non-small cell lung cancer: experience at a teaching hospital.

BACKGROUND: The management of patients with metastatic non-small cell lung cancer (NSCLC) is complex. Some studies have demonstrated that the care of patients with NSCLC may be suboptimal. AIM: To review the management of patients with metastatic NSCLC treated at a single teaching hospital over a 5-year period. METHOD: All patients with metastatic NSCLC treated at a single teaching hospital over a 5-year period (1998-2002) were identified. Data were collected by a retrospective record review. RESULTS: Of 343 patients with metastatic NSCLC, 157 patients were deemed eligible for this review. Thirty-one patients (19%) were admitted to the Medical Oncology Unit at initial presentation. Twenty-four patients (15%) were not referred to either the Medical Oncology Unit or the Palliative Care Unit. Forty-four patients (28%) received chemotherapy, six of whom (14%) were enrolled onto a clinical trial. Six separate chemotherapy regimens were used. The median survival was 5 months and the 1-year survival rate was 19.8%. CONCLUSIONS: The present audit demonstrates some shortfalls in the optimal clinical care of patients with metastatic NSCLC at a large teaching hospital. The main selection criteria of consideration for chemotherapy are age, performance status and presence of symptoms. A subset of patients was not referred to either the Medical Oncology Unit or the Palliative Care Unit and consistency in the choice of chemotherapy was lacking. Survival data and the rate of patients entered onto clinical trials are acceptable; however, further improvements can be made by the institution of multidisciplinary clinics and the education of referring clinicians.

A randomized double-blind multicenter phase III study of fixed-dose single-administration pegfilgrastim versus daily filgrastim in patients receiving myelosuppressive chemotherapy.

BACKGROUND: We evaluated the efficacy of a single fixed 6 mg dose of pegfilgrastim (a pegylated version of filgrastim) per cycle of chemotherapy, compared with daily administration of filgrastim, in the provision of neutrophil support. PATIENTS AND METHODS: Patients (n = 157) were randomized to receive either a single 6 mg subcutaneous (s.c.) injection of pegfilgrastim or daily 5 mg/kg s.c. injections of filgrastim, after doxorubicin and docetaxel chemotherapy (60 mg/m(2) and 75 mg/m(2), respectively). Duration of grade 4 neutropenia, depth of neutrophil nadir, incidence of febrile neutropenia, time to neutrophil recovery and safety information were recorded. RESULTS: A single 6 mg injection of pegfilgrastim was as effective as daily injections of filgrastim for all efficacy measures for all cycles. The mean duration of grade 4 neutropenia in cycle 1 was 1.8 and 1.6 days for the pegfilgrastim and filgrastim groups, respectively. Results for all efficacy end points in cycles 2-4 were consistent with the results from cycle 1. A trend towards a lower incidence of febrile neutropenia was noted across all cycles with pegfilgrastim compared with filgrastim (13% versus 20%, respectively). A single fixed dose of pegfilgrastim was as safe and well tolerated as standard daily filgrastim. CONCLUSIONS: A single fixed dose of pegfilgrastim administered once per cycle of chemotherapy was comparable to multiple daily injections of filgrastim in safely providing neutrophil support during myelosuppressive chemotherapy. Pegfilgrastim may have utility in other clinical settings of neutropenia.

Treatment with the novel anti-angiogenic agent PI-88 is associated with immune-mediated thrombocytopenia.

BACKGROUND: The novel molecule PI-88 is a highly sulfonated oligosaccharide which inhibits heparanase activity and competes with heparan sulfate binding of growth factors such as FGF and VEGF. Preclinical data demonstrates that PI-88 inhibits angiogenesis and has anti-metastatic effects. The aim of this phase I study was to determine the recommended dose and toxicity profile of PI-88. PATIENTS AND METHODS: PI-88 was given intravenously in increasing duration of administration (0.57 mg/kg for 2 h, 0.57 mg/kg/day for 1 day, 4, 7 and 14 consecutive days) and then increasing dose for 14 consecutive days (1.14 mg/kg/day and 2.28 mg/kg/day) in patients with advanced malignancies until dose-limiting toxicity (DLT) was observed. Fourteen assessable patients with advanced malignancies received PI-88 intravenously. RESULTS: DLT was thrombocytopenia. The thrombocytopenia appeared to be immunologically mediated with the development of anti-heparin platelet factor 4 complex antibodies. There were no other significant toxicities. At the final dose and schedule (2.28 mg/kg/day for 14 days), there was limited evidence of biological activity as measured by the surrogate marker activated partial thromboplastin time (APTT), although two patients had stabilisation of disease. CONCLUSIONS: In conclusion, PI-88 at a dose of 2.28 mg/kg/day for 14 days resulted in dose-limiting thrombocytopenia which appeared to be immune related. Limited evidence of biological activity was noted. Alternate scheduling and routes of administration are now being explored.

Authentication of artemether, artesunate and dihydroartemisinin antimalarial tablets using a simple colorimetric method.

The recent and widespread appearance of counterfeit antimalarial tablets in South-east Asia prompted the search for simple field assays to identify genuine drugs. In a recently described colorimetric assay for artesunate, Fast red TR salt reacted with an alkali-decomposition product of artesunate to produce a distinct yellow colour. However, that assay is specific for artesunate and it cannot be used to test for artemether. Because of potential concerns over artemether tablet counterfeiting, the colorimetric assay was modified to detect artemether, dihydroartemisinin and artesunate tablets. Other common antimalarials (artemisinin, chloroquine diphosphate, mefloquine HCl, sulphadoxine and pyrimethamine), as well as aspirin and acetaminophen, were negative in the assay, indicating its specificity for artemether, dihydroartemisinin and artesunate. The colorimetric method can be used to obtain a rapid visual assessment of tablet authenticity. The method can also be used to quantify the drug content of tablets, when used in conjunction with a spectrophotometer.

Phase II clinical trial of preoperative combined chemoradiation for T3 and T4 resectable rectal cancer: preliminary results.

PURPOSE: Although preoperative chemoradiation for high-risk rectal cancer may improve survival and local recurrence rate, its adverse effects are not well defined. This prospective study evaluated the use of preoperative chemoradiation for T3 and T4 resectable rectal cancer, with special emphasis on treatment morbidity, pathologic remission rate, quality of life, and anorectal function. METHODS: Forty-two patients (30 men, 12 women) were enrolled in the study. Median distance of the distal tumor margin from the anal verge was 6.5 cm. Preoperative staging was based on digital rectal examination, endorectal ultrasound, and computed tomography. None of the patients had distant metastases. All patients had 45 Gy (1.8 Gy/day in 25 fractions) over five weeks, plus 5-fluorouracil (350 mg/m(2)/day) and leucovorin (20 mg/m(2)/day) bolus on days 1 to 5 and 29 to 33. Quality of life was assessed with the European Organization for Research and Treatment of Cancer 30-item quality-of-life questionnaire (QLQ-C30) and its colorectal cancer-specific module (QLQ-CR38) questionnaires. Objective anorectal function was assessed by anorectal manometry and pudendal nerve terminal motor latency. Surgery was performed 46 (range, 24-63) days after completion of adjuvant therapy. RESULTS: Nineteen patients (45 percent) had Grade 3 or 4 chemoradiation-induced toxic reactions. Four patients developed intercurrent distant metastases or intraperitoneal carcinomatosis at completion of chemoradiation. Thirty-eight patients underwent surgical resection: abdominoperineal resection, anterior resection, and Hartmann's procedure were performed in 55 percent, 39 percent (11 of 15 patients had a diverting stoma), and 5 percent, respectively. Major surgical complications occurred in 7 patients (18 percent) and included anastomotic leak (n = 1), pelvic abscess (n = 1), small-bowel obstruction (n = 3), and wound breakdown (n = 2). Final pathology was Stage 0 (no residual disease), I, II, and III in 6 (16 percent), 7 (18 percent), 9 (24 percent), and 16 (42 percent) patients, respectively. There was a deterioration, after chemoradiation and surgery, in the quality of life on all subscales assessed, with physical, role, and social function being most severely affected. The symptoms most adversely affected were micturition, defecation, and gastrointestinal problems. Body image and sexual enjoyment deteriorated in both men and women. Chemoradiation alone led to prolonged pudendal nerve terminal motor latency in 57 percent of 7 patients assessed. CONCLUSION: Preliminary results have identified defined costs with preoperative chemoradiation, which included treatment-induced toxicity, a high stoma rate, and adverse effects on quality of life and anorectal function.

Analysis of opioid binding to UDP-glucuronosyltransferase 2B7 fusion proteins using nuclear magnetic resonance spectroscopy.

The UDP-glucuronosyltransferase UGT2B7 is an important human UGT isoform that catalyzes the conjugation of many endogenous and exogenous compounds, among them opioids, resulting in the formation of D-glucuronides. The binding site of the aglycone is located in the N-terminal half of the protein. In this study, we demonstrate that the opioid binding site in UGT2B7 is within the first 119 amino-terminal amino acids. Two maltose binding protein fusion proteins, 2B7F1 and 2B7F2, incorporating the first 157 or 119 amino acids, respectively, of UGT2B7 were expressed in Escherichia coli and purified by affinity chromatography. NMR spectroscopy using one-dimensional spectra, the inversion recovery method, and the transferred nuclear Overhauser effect spectroscopy was used to study the binding properties of opioids to the fusion proteins. Morphine was found to bind at a single site within the first 119 amino acids and to undergo a conformational change upon binding, as demonstrated by transferred nuclear Overhauser effect spectroscopy. Dissociation constants were obtained for morphine, naloxone, buprenorphine, and zidovudine, and the results were confirmed by equilibrium dialysis determinations. Two possible opioid binding sites, based on the nearest neighbors from opioid binding to the micro-receptor and to cytochrome 2D6, are proposed.

Epirubicin glucuronidation is catalyzed by human UDP-glucuronosyltransferase 2B7.

Epirubicin is one of the most active agents for breast cancer. The formation of epirubicin glucuronide by liver UDP-glucuronosyltransferase (UGT) is its main inactivating pathway. This study aimed to investigate epirubicin glucuronidation in human liver microsomes, to identify the specific UGT isoform for this reaction, and to correlate epirubicin glucuronidation with other UGT substrates. Microsomes from human livers were used. UGTs specifically expressed in cellular systems, as well as two UGT2B7 variants, were screened for epirubicin glucuronidation. Epirubicin, morphine, and SN-38 glucuronides were measured by high-pressure liquid chromatography. The mean +/- S.D. formation rate of epirubicin glucuronide in human liver microsomes (n = 47) was 138 +/- 37 pmol/min/mg (coefficient of variation, 24%). This phenotype was normally distributed. We screened commercially available UGT1A1, UGT1A3, UGT1A4, UGT1A6, UGT1A9, UGT2B7, and UGT2B15 for epirubicin glucuronidation. Only UGT2B7 converted epirubicin to its glucuronide. No differences in epirubicin glucuronidation were found in HK293 cells expressing the two UGT2B7 variants at position 268. Catalytic efficiency (V(max)/K(m)) of epirubicin glucuronidation was 1.4 microl/min/mg, a value higher than that observed for morphine, a substrate of UGT2B7. Formation of epirubicin glucuronide was significantly related to that of morphine-3-glucuronide (r = 0.76, p < 0.001) and morphine-6-glucuronide (r = 0.73, p < 0.001). No correlation was found with SN-38, a substrate of UGT1A1 (r = 0.04). UGT2B7 is the major human UGT catalyzing epirubicin glucuronidation, and UGT2B7 is the candidate gene for this phenotype. The reported tyrosine to histidine polymorphism in UGT2B7 does not alter the formation rate of epirubicin glucuronide, and undiscovered genetic polymorphisms in UGT2B7 might change the metabolic fate of this important anticancer agent.