Baseline Albumin Concentrations Research Articles

Population pharmacokinetic modeling of sotatercept in healthy participants and patients with pulmonary arterial hypertension.

Sotatercept is a breakthrough, first-in-class biologic, that is FDA-approved for the treatment of pulmonary arterial hypertension (PAH). A population pharmacokinetic (PopPK) model was developed using data from two phase 1 studies in healthy participants, and two phase 2 studiesand one phase 3 study in participants with PAH. The pooled sotatercept PK data encompassed single intravenous (IV) or subcutaneous (SC) doses ranging from 0.01 to 3.0 mg/kg, as well as multiple SC doses ranging from 0.03 to 1.0 mg/kg, with PK samples collected up to a maximum of ~150 weeks following Q3W and Q4W dosing regimens. The final PopPK analysis included 350 participants, with 30 and 320 participants receiving sotatercept IV and SC, respectively. A two-compartment model with a first-order absorption rate constant and a linear disposition from central compartment well-described sotatercept PK. The estimated bioavailability is ~66%; bioavailability, clearance (CL), and central volume (VC) have low to moderate inter-individual variability. Time-varying body weight and baseline albumin concentration were statistically significant predictors of PK; CL and VC were predicted to increase with increasing body weight, while CL was predicted to decrease with increasing baseline albumin concentration. However, the magnitude of covariate effects is not predicted to meaningfully alter the disposition of sotatercept. Altogether, the PopPK modeling results demonstrate favorable PK characteristics (low to moderate variability and typical bioavailability), supporting sotatercept as a SC biological agent for the treatment of patients with PAH.

Expert Consensus on the Use of Human Serum Albumin in Adult Cardiac Surgery.

Expert Consensus on the Use of Human Serum Albumin in Adult Cardiac Surgery.

Pre-procedural serum albumin concentration is associated with length of stay, discharge destination, and 90-day mortality in patients after transcatheter aortic valve replacement.

As visceral protein expression may influence outcomes in patients with cardiovascular disease, we investigated whether pre-procedural albumin concentration is associated with length of stay (LOS) and 90-day mortality after transcatheter aortic valve repair (TAVR). We retrospectively analyzed data from TAVR patients at our institution between January 2013 and December 2017. For all patients, baseline albumin concentration was assessed between one and four weeks before the procedure. To investigate the association between albumin concentration and outcomes, we performed regression analyses, controlling for Society of Thoracic Surgeons, New York Heart Association classification, and Kansas City Cardiomyopathy Questionnaire 12 scores. Three hundred eighty patients were included in the analyses. Cox-proportional hazards regression showed that patients with albumin concentrations <3.5 g/dL were 80% more likely to have prolonged ICU LOS (HR 1.79; 95%CI 1.04-2.57, P = 0.03) and 70% more likely to have prolonged hospital LOS (HR 1.68; 95%CI 1.01-2.46, P = 0.04) compared to patients with albumin concentrations >3.5 g/dL. Logistic regression showed that patients with albumin concentrations <3.5 g/dL were four times more likely to not survive to 90 days (OR 3.94; 1.13-12.63, P = 0.03) after their TAVR compared to patients with albumin concentrations >3.5 g/dL. Our data suggest that patients with pre-procedural albumin concentrations <3.5 g/dL are at an increased risk of adverse outcomes after TAVR compared to patients with albumin concentrations ≥3.5 g/dL. Prospective studies are needed to determine whether risk stratification based on pre-procedural albumin can improve outcomes and whether targeted interventions can improve pre-procedural albumin concentrations in potential TAVR candidates.

Population pharmacokinetics and exposure-response of trilaciclib in extensive-stage small cell lung cancer and triple-negative breast cancer.

Trilaciclib is a first-in-class, intravenous cyclin-dependent kinase 4/6 inhibitor that provides multilineage protection from chemotherapy-induced myelosuppression. This analysis aimed to characterize the population pharmacokinetics (PK) of trilaciclib, identify potential covariates influencing trilaciclib PK, and evaluate exposure-response relationships in extensive-stage small cell lung cancer (ES-SCLC) and triple-negative breast cancer (TNBC) trials. Population PK analysis was performed using data from healthy volunteers (n = 72), patients with ES-SCLC (n = 111) and patients with TNBC (n = 14). Exposure-response analyses were conducted to investigate the impact of trilaciclib exposure (AUC) on myeloprotective efficacy, antitumour efficacy and safety. Logistic regression and Cox regression models were used for binary and time-to-event endpoints, respectively. Trilaciclib PK was described by a three-compartment model. Sex, body surface area, baseline albumin concentration and age were identified as significant covariates on trilaciclib PK but did not have clinically relevant impact on exposure. Based on exposure-response analyses, lower and higher exposures of trilaciclib at clinical doses (200-280 mg/m2 ) were associated with similar myeloprotective effects. Trilaciclib exposure did not impact the antitumour effects of chemotherapy. Higher exposure to trilaciclib was associated with higher probabilities of headache, phlebitis/thrombophlebitis and injection site reactions. No dose adjustments are required based on the covariates tested. Trilaciclib resulted in optimal myeloprotective effects with no impact on antitumour effects of chemotherapy. However, higher exposure increased the probabilities of adverse events. The data further support selection of the recommended phase 2 dose (trilaciclib 240 mg/m2 ).

Risk Factors for Tigecycline-Associated Hepatotoxicity in Patients in the Intensive Care Units of 2 Tertiary Hospitals: A Retrospective Study.

Tigecycline is a broad-spectrum antibacterial agent. As the incidence of multidrug-resistant bacterial infections has increased in intensive care units (ICUs) over the past decades, tigecycline is often used in ICUs. Information about tigecycline-associated hepatotoxicity in ICU patients is limited. To investigate the potential risk factors for tigecycline-associated hepatotoxicity in ICU patients, 148 patients from 2 centers who had received tigecycline for at least 4 days were retrospectively analyzed. Hepatotoxicity was classified according to the National Cancer Institute Common Terminology Criteria for Adverse Events (5.0) grading system. As a result, 33.8% of patients experienced hepatotoxicity events in the ICU. The multivariate analysis showed that an albumin concentration <25 g/L at baseline (odds ratio, 3.714; 95%CI, 1.082-12.744; P = .037) and treatment duration (odds ratio, 1.094; 95%CI, 1.032-1.160; P = .003) were significantly correlated with tigecycline-associated hepatotoxicity. The median time to onset of hepatotoxicity was 8.0 days. The median duration ICU stay and the in-hospital mortality rate were not different between the hepatotoxicity group and the nonhepatotoxicity group (33.5 days (interquartile range, 21.0-72.0) vs 31.0 days (interquartile range, 21-62.5), P = .850; 38.0% vs 43.8%; P = .504). Therefore, close monitoring of liver function is recommended for patients with baseline albumin concentrations <25 g/L or for patients who receive tigecycline therapy for >8 days.

The Predictive Value of Changes in Body Mass Index for the Incidence of Device-Specific Infections in Patients With Implantable Left Ventricular Assist Devices.

Implantable left ventricular assist devices (LVAD) have improved quality of life and survival in patients with advanced heart failure. However, LVAD-specific infections and predicting which patients will develop infections remain challenging. This study investigated whether changes in body mass index (BMI) during hospitalization following LVAD implantation are associated with LVAD-specific infections within 1 year of implantation. Patients (n=135) undergoing LVAD implantation were retrospectively divided into 2 groups based on changes in BMI from LVAD implantation to discharge: those with and without decreases in BMI. Each group was further subdivided according to baseline albumin concentrations (high [>3.7 g/dL] and low [≤3.7 g/dL]). Twenty patients developed LVAD-specific infections within 1 year. Receiver operating characteristic curve analysis resulted in a ∆BMI cut-off of less than -0.128 kg/m2. In multivariate analysis, younger patients and those with decreases in BMI had significantly higher rates of LVAD-specific infection (P=0.010 and P=0.035, respectively). LVAD-specific infection rates were significantly higher for patients with low albumin and decreases in BMI than for patients with low albumin but no decrease in BMI. Decreases in BMI during hospitalization after LVAD implantation and younger age were independently associated with LVAD-specific infection within 1 year. Strict patient management may be needed to avoid decreases in BMI during hospitalization after LVAD implantation, particularly in patients with low baseline albumin concentrations.

Contemporary mortality after emergent open repair of complex abdominal aortic aneurysms

ObjectiveMortality after open repair for emergent complex abdominal aortic aneurysm (AAA) is poorly defined. This study evaluated the 30-day mortality of open complex AAA repair performed for rupture or other emergent indication using a national surgical registry. We subsequently identified factors associated with mortality. MethodsThe targeted vascular module from the American College of Surgeons National Surgical Quality Improvement Program was queried to identify patients undergoing open repair for juxtarenal and suprarenal AAAs or type IV thoracoabdominal aneurysms (TAAAs) for rupture or other emergent indication from 2011 to 2017. Univariate analyses were performed using the Fisher's exact test for categorical variables and the Wilcoxon rank sum test for continuous variables. Multivariable logistic regression was performed to identify factors independently associated with mortality. ResultsWe included 374 patients who underwent an emergent complex open AAA repair during the study period. There were 142 (38%) cases performed for rupture with hypotension, 141 (38%) for rupture without hypotension, 40 (11%) for symptomatic AAA, and 51 (14%) for another indication. The distribution by aneurysm type was 224 juxtarenal AAAs, 122 suprarenal AAAs, and 28 type IV TAAAs. Overall, there was a 30-day mortality of 32% (118 deaths). For those with juxtarenal AAA repair, 67 (30%) patients died within 30 days; there were 38 (31%) deaths within 30 days in those with suprarenal AAA, and 13 (46%) deaths within 30 days in those with type IV TAAA. On univariate analysis, preoperative variables associated with death were increasing age, use of a transperitoneal surgical approach, lower preoperative estimated glomerular filtration rate, low baseline albumin concentration (<3.5 g/dL), need for preoperative transfusion, low body mass index (<18.5 kg/m2), and hypotension at presentation. Intraoperative variables associated with mortality were supraceliac clamp location and concurrent renal revascularization. On multivariable analysis, factors independently associated with death included rupture with associated hypotension (reference: other emergent indication; adjusted odds ratio [AOR], 3.28; confidence interval [CI], 1.75-5.41; P < .001), age >60 years (reference: <60 years; AOR, 1.59; CI, 1.18-2.13; P = .002), longitudinal laparotomy incision (reference: retroperitoneal; AOR, 3.28; CI, 1.75-6.16; P < .001), and supraceliac cross-clamp (reference: clamp above one renal artery; AOR, 2.14; CI, 1.31-3.50; P = .003). ConclusionsNearly one-third of patients die within 30 days of emergent open complex AAA repair. Mortality is particularly high for patients with type IV TAAAs, approaching 50%. Predictors of 30-day mortality include rupture with associated hypotension, increasing age, supraceliac clamp location, and longitudinal transperitoneal repair approach. These results will help inform surgical decisions preoperatively and intraoperatively.

Development and Validation of Clinical Scoring Tool to Predict Outcomes of Treatment With Vedolizumab in Patients With Ulcerative Colitis

BACKGROUND & AIMS:We created and validated a clinical decision support tool (CDST) to predict outcomes of vedolizumab therapy for ulcerative colitis (UC).METHODS:We performed logistic regression analyses of data from the GEMINI 1 trial, from 620 patients with UC who received vedolizumab induction and maintenance therapy (derivation cohort), to identify factors associated with corticosteroid-free remission (full Mayo score of 2 or less, no subscore above 1). We used these factors to develop a model to predict outcomes of treatment, which we called the vedolizumab CDST. We evaluated the correlation between exposure and efficacy. We validated the CDST in using data from 199 patients treated with vedolizumab in routine practice in the United States from May 2014 through December 2017.RESULTS:Absence of exposure to a tumor necrosis factor (TNF) antagonist (+3 points), disease duration of 2 y or more (+3 points), baseline endoscopic activity (moderate vs severe) (+2 points), and baseline albumin concentration (+0.65 points per 1 g/L) were independently associated with corticosteroid-free remission during vedolizumab therapy. Patients in the derivation and validation cohorts were assigned to groups of low (CDST score, 26 points or less), intermediate (CDST score, 27–32 points), or high (CDST score, 33 points or more) probability of vedolizumab response. We observed a statistically significant linear relationship between probability group and efficacy (area under the receiver operating characteristic curve, 0.65), as well as drug exposure (P < .001) in the derivation cohort. In the validation cohort, a cutoff value of 26 points identified patients who did not respond to vedolizumab with high sensitivity (93%); only the low and intermediate probability groups benefited from reducing intervals of vedolizumab administration due to lack of response (P = .02). The vedolizumab CDST did not identify patients with corticosteroid-free remission during TNF antagonist therapy.CONCLUSIONS:We used data from a trial of patients with UC to develop a scoring system, called the CDST, which identified patients most likely to enter corticosteroid-free remission during vedolizumab therapy, but not anti-TNF therapy. We validated the vedolizumab CDST in a separate cohort of patients in clinical practice. The CDST identified patients most likely to benefited from reducing intervals of vedolizumab administration due to lack of initial response. ClinicalTrials.gov no: NCT00783718

Serum Asunaprevir and Daclatasvir Concentrations and Outcomes in Patients with Recurrent Hepatitis C Who Have Undergone Living Donor Liver Transplantation.

This study's aim was to investigate the safety and effectiveness of asunaprevir and daclatasvir treatment for recurrent hepatitis C virus (HCV) infection in transplant recipients. The study cohort comprised 14 transplant recipients with recurrent hepatitis C who were receiving asunaprevir and daclatasvir. Serum concentrations of asunaprevir and daclatasvir, their therapeutic effects, trough concentrations/dose ratios of tacrolimus, and adverse effects were evaluated. Hepatitis C virus was still undetectable in 12 (85.7%) out of 14 patients 12 weeks after completing treatment. One week after starting treatment, asunaprevir concentrations were significantly higher in patients with baseline albumin concentrations ≤3.6 g/dl than in those with baseline albumin concentrations >3.6 g/dl. No marked fluctuations were identified in tacrolimus trough concentrations/dose ratios during the 24 weeks of therapy. Full doses of asunaprevir and daclatasvir-based treatment can be safely and effectively administered to liver transplant recipients for recurrent HCV genotype 1b after living donor liver transplantation (LDLT) with little effect on blood concentrations of tacrolimus.

Pharmacokinetics and C-reactive protein modelling of anti-interleukin-6 antibody (PF-04236921) in healthy volunteers and patients with autoimmune disease.

The purpose of this study was to characterize pharmacokinetics (PK) of PF-04236921, a novel anti-interleukin-6 monoclonal antibody, and its pharmacokinetic/pharmacodynamic (PK/PD) relationship on serum C-reactive protein (CRP) in healthy volunteers and patients with rheumatoid arthritis (RA), systemic lupus erythematosus (SLE) and Crohn's disease (CD). Population modelling analyses were conducted using nonlinear mixed effects modelling. Data from two phase 1 healthy volunteer studies, a phase 1 RA study, a Phase 2 CD study and a Phase 2 SLE study were included. A two-compartment model with first order absorption and linear elimination and a mechanism-based indirect response model adequately described the PK and PK/PD relationships, respectively. Central compartment volume of distribution (Vc) positively correlated with body weight. Clearance (CL) negatively correlated with baseline albumin concentration and positively correlated with baseline CRP and creatinine clearance, and was slightly lower in females. After correcting for covariates, CL in CD subjects was approximately 60% higher than other populations. Maximum inhibition of PF-04236921 on CRP production (Imax ) negatively correlated with baseline albumin. Imax positively correlated with baseline CRP and the relationship was captured as a covariance structure in the PK/PD model. Integrated population PK and PK/PD models of PF-04236921 have been developed using pooled data from healthy subjects and autoimmune patients. The current model enables simulation of PF-04236921 PK and PD profiles under various dosing regimens and patient populations and should facilitate future clinical study of PF-04236921 and other anti-interleukin-6 monoclonal antibodies.

Association of low serum albumin concentration and adverse cardiovascular events in stable coronary heart disease

ObjectiveCoronary heart disease (CHD) is a leading cause of death in developed countries. Exploration of indicators to identify high risk individuals who develop adverse outcomes despite stable baseline condition is important. This study is to evaluate the association between serum albumin concentration and cardiovascular (CV) outcomes in individuals of stable CHD. MethodsSeven-hundred–thirty-four participants from Biosignature study, a nationwide prospective cohort study aimed to identity risk factors among patients with stable CHD, were enrolled for analysis. They were divided into low serum albumin group (baseline albumin concentration <3.5g/dL, n=98) and normal albumin group (baseline albumin concentration ≥3.5g/dL, n=636). The relations between baseline albumin and adverse CV outcomes within 18months of follow-up were analyzed. ResultsCompared baseline characteristics with normal albumin group, subjects in low albumin group are older, having more diabetic patients, lower hemoglobin level, lower estimated glomerular filtration rate, lower total cholesterol level, lower left ventricular ejection fraction, and higher blood glucose. While there is no significant difference of total CV events between two groups, low serum albumin concentration is associated with an increased risk of all-cause mortality (10.2% vs. 0.5%, p<0.001) and hard CV events (7.1% vs. 1.4%, p<0.001). The association remains significant after adjustments for confounders (all-cause mortality, HR: 6.81, 95% CI: 1.01–45.62; hard CV events, HR: 3.68, 95% CI: 1.03–13.19). ConclusionsLow serum albumin concentration (<3.5g/dL) worsens prognosis of patients with stable CHD.

Hyperuricemia is associated with progression of IgA nephropathy.

IgA nephropathy (IgAN) is one of the world's most common glomerular diseases. Hyperuricemia was recently defined as risk factor for chronic kidney disease. We aimed to investigate the impact of baseline serum uric acid levels on progression of IgAN. A total of 93 patients with IgAN were screened. Demographic information and biochemical data were recorded. eGFR (using the CKD-EPI = Chronic Kidney Disease Epidemiology Collaboration formula) was used as renal function marker. Baseline and sixth month eGFR values were calculated. Progression of renal disease was defined as the difference between baseline eGFR and sixth month eGFR (delta eGFR). Mean age of the patients was 40 ± 11 years (60% were males). Baseline mean eGFR was 77.9 ± 30.2 mL/min, and baseline mean serum uric acid was 5.65 ± 1.68 mg/dL. Importantly, baseline serum uric acid levels were found to be associated with the change in eGFR (r = 0.252, p = 0.01). In multivariate analysis (adjusted R(2) = 0.171, p = 0.031), adjusting for age, gender, baseline eGFR, blood pressure, baseline albumin concentration and ACEI and/or ARB use revealed that the baseline serum uric acid levels significantly predicted the change in eGFR. Baseline serum uric acid concentration is directly proportional to the rate of decline in renal functions in patients with IgAN. Uric acid-lowering treatments may be beneficial for the prevention of progression of IgAN. However, randomized controlled studies are needed for this purpose.

Abstract P303: Low Albumin and Risk of Type 2 Diabetes

Type 2 diabetes (T2DM) is a burdensome, costly and debilitating disease that causes premature morbidity and mortality. Recent evidence suggests that T2DM is in part an inflammatory disease. It is well known that serum albumin is a negative acute phase reactant, yet few studies have examined the association between albumin and risk of T2DM. The purpose of this analysis was to prospectively examine the association between serum albumin and incident type 2 diabetes in middle-aged and older adults from a defined population. The Western New York Health Study enrolled apparently healthy participants ages 35-79 yrs from Niagara and Erie counties, NY. For this report, at baseline (1996-2001) all participants from the Western New York Health Study had fasting plasma glucose &lt;110 mg/dl. At follow-up, six years later each case (n=61) was matched with up to three controls (n=158) on gender, race/ethnicity, the year of study enrollment, and baseline fasting glucose &lt;110 mg/dl or 110-125 mg/dl. Diabetes at follow-up was defined as: 1) fasting plasma glucose &gt; 125 mg/dl; 2) random glucose &gt;199 mg/dl; or 3) a physician diagnosis and receiving antidiabetic medication. Conditional logistic regression was used to estimate the odds ratio (95% CI) of developing type 2 diabetes by tertile of baseline albumin adjusted for the matching criteria and additional covariates including BMI, smoking and physical activity. Mean age was 58 years; 60% women; 93% White. Multivariate analyses indicated that cases had lower baseline albumin concentrations (OR = 0.41, 95%CI: 0.17, 0.99 (p=0.04; lowest tertile vs highest) (p trend &lt; 0.05). Further analyses indicated that this relation was independent of hs-CRP and IL-6. Stratification by smoking status did not alter the findings. The results of this analysis support the hypothesis that individuals with lower albumin concentrations were more likely to develop type 2 diabetes than those with higher levels.

Increased Gamma Globulin Following Immunotherapy with Sipuleucel-T Is Associated with Antigen-Specific Antibody Responses

AbstractAbstract 1738Sipuleucel-T is an autologous cellular immunotherapy for the treatment of asymptomatic or minimally symptomatic metastatic castrate resistant prostate cancer. Sipuleucel-T consists of autologous peripheral blood mononuclear cells (PBMCs), including antigen presenting cells (APCs), that have been activated with a recombinant human protein, PAP-GM-CSF (prostatic acid phosphatase [PAP] linked to granulocyte-macrophage colony-stimulating factor [GM-CSF]). It is prepared from cells collected by leukaphereses at Weeks 0, 2, and 4 and infused approximately 3 days following each leukapheresis. In the IMPACT study, 512 patients were randomized (2:1) to sipuleucel-T or control (non-activated autologous PBMCs). Serum samples were collected at Baseline and Weeks 6, 14, and 26, and were analyzed for routine clinical chemistry tests in a comprehensive metabolic panel, which included total protein and albumin. In selected samples, serum protein electrophoresis (SPEP) and densitometry were performed using the Sebia automated electrophoresis system. We observed elevated total protein at Weeks 6 and 14 in sipuleucel-T patients only. At Week 6, 10.0% (28/279) of sipuleucel-T patients with a normal baseline total protein concentration had an elevated total protein concentration (upper limit of normal [ULN] = 7.9 to 8.5 g/dL, depending on age) compared with 0% (0/140) of control patients. At Week 14, 10.4% (19/183) of sipuleucel-T patients with a normal baseline total protein had an elevated total protein compared with 0% (0/86) of control patients. Albumin levels were not elevated at Week 6 following treatment (0.4% ½84 of sipuleucel-T patients with a normal baseline albumin concentration had increases in post-treatment serum albumin), indicating that the changes in total protein were due to elevations in serum globulin. In sipuleucel-T patients, there was a positive correlation between the maximum globulin protein elevations (total protein minus albumin) and the magnitude of antibody titers to PAP-GM-CSF at Week 6 (n = 126; P = 0.001) and Week 14 (n = 85; P = 0.002). Samples from sipuleucel-T patients for whom both a baseline and post-treatment sample were available and who fell within the upper 10th percentile of the total protein change (n = 13) were evaluated by SPEP. All of these patients had increased gamma globulin compared with baseline. Nine patients (69.2%) developed gamma globulin above the upper limit of normal (i.e., > 1.5 g/dL) which was not present at baseline. A correlation between gamma globulin elevations and antibody titers to PAP-GM-CSF in these patients (n = 9) was observed at Week 6 (r = 0.664, P = 0.051). These data demonstrate that elevated gamma globulin levels can develop following treatment with sipuleucel-T and were associated with the development of an antigen-specific humoral response. Disclosures:Sims:Dendreon Corp.: Employment. dela Rosa:Dendreon Corp.: Employment. Lin:Dendreon Corp.: Employment. Sheikh:Dendreon Corp.: Employment.

“Losing one's chops”

Background/Aim: This study9s aim was to investigate the safety and effectiveness of asunaprevir and daclatasvir treatment for recurrent hepatitis C virus (HCV) infection in transplant recipients. The study cohort comprised 14 transplant recipients with recurrent hepatitis C who were receiving asunaprevir and daclatasvir. Patients and Methods: Serum concentrations of asunaprevir and daclatasvir, their therapeutic effects, trough concentrations/dose ratios of tacrolimus, and adverse effects were evaluated. Results: Hepatitis C virus was still undetectable in 12 (85.7%) out of 14 patients 12 weeks after completing treatment. One week after starting treatment, asunaprevir concentrations were significantly higher in patients with baseline albumin concentrations ≤3.6 g/dl than in those with baseline albumin concentrations &gt;3.6 g/dl. No marked fluctuations were identified in tacrolimus trough concentrations/dose ratios during the 24 weeks of therapy. Conclusion: Full doses of asunaprevir and daclatasvir-based treatment can be safely and effectively administered to liver transplant recipients for recurrent HCV genotype 1b after living donor liver transplantation (LDLT) with little effect on blood concentrations of tacrolimus.

Serum albumin concentration: a predictive factor of infliximab pharmacokinetics and clinical response in patients with ulcerative colitis

Infliximab, an IgG1 monoclonal antibody (mab), has large inter-individual serum concentration variability. The objective was to determine the extent of the association of baseline albumin concentration and infliximab disposition in patient with ulcerative colitis. Data from 728 patients with ulcerative colitis from two clinical trials were analyzed to evaluate trends between infliximab pharmacokinetics and serum albumin, or liver or kidney function. Response in the placebo and treated groups were compared by baseline serum albumin concentrations (SAC) groups. Patients with higher SAC maintained higher infliximab concentrations, lower clearance, and longer half-life than patients with lower SAC. When analyzed by SAC quartiles, patients in the highest quartile had several-fold greater trough infliximab concentrations when compared with those in the lowest quartile. These observations were consistent in both studies and at different dose levels. Generally, clinical response in patients did not vary with SAC when the SAC was within the normal range, apparently because serum infliximab concentrations remained at therapeutic levels. However, patients with SAC lower than the normal laboratory reference range had much lower median serum infliximab concentrations and lower response rates compared with patients within normal SAC. Infliximab pharmacokinetics did not correlate with SGOT or creatinine clearance. It is hypothesized that the common rescue pathway for both albumin and IgG involving the neonatal Fc receptor may be responsible for the relationship between serum albumin and serum infliximab levels. Baseline albumin level may serve as a valuable and convenient measure of mab pharmacokinetic expectations in these patients.