Doses required to achieve desired vancomycin concentrations are similar in morbidly obese and normal weight patients when TBW is used as a dosing weight for the obese (approximately 30 mg x kg(-1) x d(-1)). Shorter dosage intervals may be needed when dosing morbidly obese patients so that steady-state trough concentrations remain above 5 microg x ml(-1) in this population. Because of the large amount of variation in required doses, vancomycin serum concentrations should be obtained in morbidly obese patients to ensure that adequate doses are being administered. Dosage requirements for morbidly obese patients with renal dysfunction require further study.

Ten healthy adults participated in a randomized, crossover drug interaction study testing procainamide only, procainamide plus levofloxacin, and procainamide plus ciprofloxacin. During levofloxacin therapy, most procainamide and N-acetylprocainamide (NAPA) pharmacokinetic parameters, including decreased renal clearances and renal clearance/creatinine clearance ratios, changed (P < 0.05). During ciprofloxacin treatment, only procainamide and NAPA renal clearances decreased significantly.Renal drug interactions in patients are often overlooked when new drug therapy is added to existing therapeutic regimens. Procainamide, N-acetylprocainamide (NAPA; the active metabolite of procainamide), and several fluoroquinolone antibiotics are eliminated renally by active tubular secretion (9,11,15,16,21). Procainamide serum concentrations increase and its pharmacokinetics change due to concurrent therapy with ofloxacin (15). The purpose of this study was to investigate the possibility of a renal drug interaction between procainamide and levofloxacin, one of the stereoisomers of ofloxacin. For comparison, the potential for a ciprofloxacin-procainamide drug interaction was also studied.(A portion of this work was presented in abstract form at the 2001 American College of Clinical Pharmacology Annual Meeting, Tampa, Fla.)Ten healthy adults (five males, five females; ages, 21 to 35 years; weights, 52 to 87 kg; seven Caucasians, three Asians) participated in the study. The investigation was approved by the university human subjects committee, and subjects provided written informed consent. All individuals had normal physical examinations, laboratory screening tests (serum electrolytes, renal and liver function tests, and complete blood cell counts), and 12-lead electrocardiograms. Subjects were within 20% of their ideal body weight, did not smoke tobacco-containing products, had no known allergy to study medications, took no additional medications, and, if female, had negative serum pregnancy tests (6). Beverages containing alcohol or methylxanthines were not allowed during the study period.The study was a three-way randomized, controlled trial designed to investigate a potential drug interaction between procainamide and two fluoroquinolone antibiotics. Subjects were not blinded from antibiotic study drugs because of obvious differences in dosage forms and administration schedules. Each of the following procedures was performed with procainamide alone (control phase) or on the fifth day of fluoroquinolone oral administration (500 mg of levofloxacin every day at 0800 h and 500 mg of ciprofloxacin every 12 h at 0800 h and 2000 h). Prior to admission to the Clinical Research Center for administration of procainamide, subjects were allowed to selfadminister the fluoroquinolone at home; compliance was assured by inspection of a medication administration diary, tablet counts of doses remaining in the pill vial, and subject interviews by investigators. In order for the study to proceed, all drug doses needed to be administered within 15 ...

No abstract

No abstract

The objective of this study was to assess the pharmacokinetics of diclofenac sodium and its five metabolites following administration of a 150 mg oral dose to healthy subjects and patients with either chronic active hepatitis of varying morphology or alcoholic cirrhosis. Six healthy subjects, 6 chronic active hepatitis patients, and 6 alcoholic cirrhosis patients were enrolled in this prospective, open-label, parallel study. Blood samples were drawn at 0, 0.25, 0.5, 0.75, 1, 2, 4, 6, 8, 12, 24, 48, 72, 144, 312, and 480 hours, and urine samples were collected for 144 hours after administration of a single oral dose of diclofenac sodium. The mean area under the serum concentration-time curve extrapolated to infinity, oral clearance, half-life, maximal concentration, and time to peak concentration for diclofenac and its metabolites were determined and compared using analysis of variance. Cirrhotics had a mean +/- SD diclofenac AUC value (19,114 +/- 6806 ng.h/ml) significantly different (p < 0.02) from hepatitis patients (6071 +/- 1867 ng.h/ml) and healthy subjects (7008 +/- 2006 ng.h/ml), whereas healthy subjects and hepatitis patients had similar values. Comparable results were found for 4'-hydroxydiclofenac. The AUC values for 3'-hydroxydiclofenac and 3'-hydroxy-4'methoxydiclofeanc were significantly different when healthy subjects were compared to cirrhotics. However, hepatitis subjects were not significantly different from either group. The results indicate that hepatitis does not alter the pharmacokinetics of diclofenac. Alcoholic cirrhosis increased the mean diclofenac AUC approximately three times compared to normal subjects, indicating that one-third of the usual dose in cirrhotics would produce equivalent AUC values in normal subjects and subjects with alcoholic cirrhosis. However, since pharmacodynamic measurements were not made and no increase in untoward or side effects was noted in the alcoholic cirrhosis patients after a single dose, maintenance doses should be titrated to patients response.

320 Background: Sip-T is an autologous cellular immunotherapy approved by the FDA for the treatment of asymptomatic or minimally symptomatic metastatic castration-resistant prostate cancer. PROCEED (NCT01306890) is a phase 4 registry evaluating men receiving sip-T therapy in the US. Patient characteristics and treatment trends were assessed from 2011 to 2013, when several agents with an overall survival benefit became commercially available. Methods: For patients enrolled from 2011 to 2013, baseline patient and disease characteristics at the first sip-T infusion, trends in prior therapy, and pre–sip-T baseline prostate-specific antigen (PSA) levels were examined year over year. Results: From 2011 to 2013, 1902 patients were enrolled and received ≥ 1 sip-T infusion: 2011, n = 145; 2012, n = 967; 2013, n = 790. During this time period, enrollment of African American men nearly doubled from 6.9% to 13.4%, and central venous catheter use to facilitate sip-T infusion decreased (from 53.8% to 44.1%). Median baseline lactate dehydrogenase (LDH) levels and the number of lymph node metastases also decreased as well as median baseline PSA values (17.8 ng/mL to 11.9 ng/mL [P = 0.002]). Prior use of first-generation anti-androgens (from 73.1% to 60.5%), ketoconazole (17.2% vs. 6.3%), and estrogen (4.8% vs. 1.6%) decreased along with prior docetaxel use (19.3% vs. 7.5%). In contrast, prior investigational use of abiraterone acetate (from 3.4% to 8.9%) and enzalutamide (1.4% vs. 3.2%) increased over time. Conclusions: Over the duration of PROCEED, the decrease in baseline PSA, lower LDH, fewer nodal metastases, and decline in prior docetaxel use suggest that sip-T is being used earlier in the course of metastatic castration-resistant disease. Moreover, second-line hormonal therapy use with agents that do not improve overall survival appears to be substituted by therapies that do. This decrease in second-line hormonal therapies during PROCEED could suggest a real-world preference for earlier sip-T use. Clinical trial information: NCT01306890.

272 Background: AA men are underrepresented in randomized clinical trials (RCTs) for prostate cancer, despite an almost 2-fold greater incidence in AA vs Caucasian populations. Sip-T is an autologous cellular immunotherapy approved by the FDA and EMA for the treatment of certain patients (pts) with asymptomatic or minimally symptomatic metastatic castration-resistant prostate cancer. AA enrollment in three sip-T phase 3 RCTs was 5.8% (n=43). While no definitive conclusions were drawn, median overall survival (OS) suggested AAs benefit from sip-T. PROCEED, an ongoing phase 4 registry, expanded efforts to increase AA enrollment to better characterize this population and the safety, product parameters (PP), and OS of AAs treated with sip-T. Methods: PROCEED enrolled 1973 pts treated with commercial sip-T within 6 months of registration. Efforts, such as selecting racially diverse sites and highlighting AA enrollment in PROCEED communications and investigator meetings, were used to boost AA enrollment. Baseline Gleason score, Eastern Cooperative Oncology Group performance status (ECOG), prostate-specific antigen (PSA), and alkaline phosphatase (ALP) were compared between RCTs and PROCEED. Safety and survival analyses are ongoing. Results: PROCEED AA enrollment was 11.7% vs 7.1% US RCT nonwhite enrollment rate and approaches the US AA population of 13.7%. Baseline AA pt characteristics were: lower median PSA and ALP levels in PROCEED vs RCTs, higher ECOG >0 in PROCEED vs RCTs, and higher Gleason score ≥8 in PROCEED vs RCTs (Table). Conclusions: Efforts to boost AA enrollment in PROCEED to a proportion comparable to the US AA population succeeded. The lower baseline PSA of AAs in PROCEED is similar to the PSA observed in the entire PROCEED population. Safety, PP, and OS will be reported with longer follow-up. Clinical trial information: NCT01306890. [Table: see text]

No abstract