Mixed Zero Research Articles

Population Pharmacokinetic and Pharmacodynamic Analysis of Polmacoxib in Healthy Volunteers and Patients With Osteoarthritis

PurposePolmacoxib, a new coxib dually inhibiting cyclooxygenase-2 and carbonic anhydrase I/II, was recently approved for osteoarthritis treatment in South Korea. This study explored the population pharmacokinetic and pharmacodynamic characteristics of polmacoxib. MethodsNonlinear mixed-effects modeling was performed using pooled pharmacokinetic data from a Phase I study in healthy individuals and pharmacokinetic properties and Western Ontario and McMaster Universities Osteoarthritis Index (WOMAC) data from a Phase IIb study in patients with osteoarthritis. Pharmacodynamic models for WOMAC were sequentially fit using individual pharmacokinetic parameter estimates. FindingsPolmacoxib concentrations in whole blood were adequately described by the 2-compartment model, with mixed zero- and first-order absorption kinetics. Iron concentration was the significant covariate associated with clearance of polmacoxib. The relationship between the whole blood concentration of polmacoxib and WOMAC was best described by a 2-effect compartment model that consisted of central and peripheral compartments with the rate constant of 0.408 min−1 for distribution to the central effect compartment. A decrease in WOMAC was linked to the central effect site compartment concentration through an ordinary maximum effect model with an effect site concentration needed to achieve 50% of the maximum effect of 508 ng/mL. ImplicationsThe current model accurately characterized the pharmacokinetic and pharmacodynamic properties of polmacoxib and could provide a basis for individualized drug therapy.

Semi-rational vector rogon–soliton solutions of the five-component Manakov/NLS system with mixed backgrounds

The five-component Manakov system (alias 5-Manakov system) appears in many fields such as nonlinear optics, Bose–Einstein condensates (alias the spin-2 Gross–Pitaevskii equation), and ocean. In this Letter, we investigate the semi-rational vector rogon–soliton and soliton of the 5-Manakov system with mixed zero and non-zero backgrounds by using the modified Darboux transform. The key point is to explicitly solve the multiple roots of a sixth degree characteristic polynomial equation. In particular, we exhibit the wave structures of the fundamental semi-rational vector rogon with grey solitons and soliton solutions, and their higher-degree forms. Moreover, the semi-rational vector rogon with grey solitons corresponding to the components with non-zero backgrounds are PT-symmetric. These semi-rational wave structures will be useful to further understand some related physical phenomena and to design the relative experiments.

Statistical Modeling of Students’ Academic Performances: A Longitudinal Study

Within students’ attrition studies, it is necessary to assess the longitudinal evolution of students within a given course of study, from enrolment to exit from the university through degree completion and academic dropout. Here, the student's academic progress is monitored through the number of courses failed each semester enrolled. The students’ failure rate and academic behavior typically provide significant insight into students’ exit outcomes from University programs. These programs usually have a maximum time frame required to complete the course. A likelihood-based approach is discussed that conditions on the exit outcome and random effects in adjusting within-subject correlation of longitudinal measurements. Ignoring the number of courses enrolled by a student may produce inadequate results on the actual failure rates. Conditioned on the exit outcomes of the student, we find out that factors such as financial aid, matriculation points, students’ race and course type registered, and gender are distinguishing factors that affect students’ academic performances, for completers and dropouts. Also, being in university-type accommodation (that often have added services such as transportation and internet connections) does not seem to significantly affect the failure rate within both groups of students. In addition, an increase in matriculation points significantly reduces the failure rate independent of the Quintile school of the student. Several count models such as mixed Poisson, mixed Zero Inflation Poisson, mixed Negative Binomial, and mixed Hurdle Poisson models are fitted and compared. In particular, the mixed Poisson model provides a better fit based on the Bayesian Information Criterion and residues analysis.

Interlinker Hydrogen Bonds Govern CO2 Adsorption in a Series of Flexible 2D Diacylhydrazone/Isophthalate-Based MOFs: Influence of Metal Center, Linker Substituent, and Activation Temperature.

Four new layered flexible metal–organic frameworks (MOFs) containing a diacylhydrazone moiety, namely, guest-filled [Zn2(iso)2(tdih)2]n (1), [Zn2(NH2iso)2(tdih)2]n (2), [Cd2(iso)2(tdih)2]n (3) and [Cd2(NH2iso)2(tdih)2]n (4) were synthesized using terephthalaldehyde di-isonicotinoylhydrazone (tdih) as a linear ditopic linker as well as isophtalate (iso) or 5-aminoisophthalate (NH2iso) as angular colinkers. The MOFs with hexacoordinated cadmium centers feature two-dimensional pore systems as compared to the MOFs with pentacoordinated zinc centers showing either zero-dimensional or mixed zero-/one-dimensional voids, as evidenced by single-crystal X-ray diffraction. In contrast to the frameworks based on isophtalates which do not show any significant gas uptakes, introduction of amino-substituted linker enables CO2 adsorption. Gently activated aminoisophthalate-based frameworks, that is, guest-exchanged in methanol and heated to 100 °C, show reversible gated CO2 adsorptions at 195 K, whereas the increase of activation temperature to 150 °C or more leads to one-step isotherms and lower adsorption capacities. X-ray diffraction and IR spectroscopy reveal significant structural differences in interlayer hydrogen bonding upon activation of materials at higher temperatures. The work emphasizes the role of hydrogen bonds in crystal engineering of layered materials and the importance of activation conditions in such systems.

Pharmacokinetics of Upadacitinib in Healthy Subjects and Subjects With Rheumatoid Arthritis, Crohn's Disease, Ulcerative Colitis, or Atopic Dermatitis: Population Analyses of Phase 1 and 2 Clinical Trials.

Upadacitinib (ABT-494) is a selective Janus kinase (JAK)1 inhibitor being developed for treatment of several inflammatory disorders. A population pharmacokinetic model was developed for upadacitinib using 11,658 plasma concentrations from 1145 subjects from 4 phase 1 and 5 phase 2 studies in healthy subjects and subjects with rheumatoid arthritis, Crohn's disease, ulcerative colitis, or atopic dermatitis. A 2-compartment model with first-order absorption and lag time for the immediate-release formulation and mixed zero- and first-order absorption with lag time for the extended-release formulation, and linear elimination adequately described upadacitinib plasma concentration-time profiles. The oral bioavailability of upadacitinib extended-release formulation was estimated to be approximately 80% relative to the immediate-release formulation. Covariates included in the final model were creatinine clearance, subject population (healthy subjects vs subjects with atopic dermatitis, ulcerative colitis, or Crohn's disease vs subjects with rheumatoid arthritis) and sex on apparent oral clearance and sex and body weight on apparent volume of distribution of the central compartment. Female subjects had 21% higher upadacitinib steady-state area under the plasma concentration-time curve (AUC) compared to male subjects. Compared to healthy subjects, subjects with atopic dermatitis, ulcerative colitis, or Crohn's disease had 21% higher upadacitinib steady-state AUC, while subjects with rheumatoid arthritis had 35% higher steady-state AUC. Subjects with mild or moderate renal impairment were estimated to have 10% or 22% higher AUC, respectively, compared to subjects with normal renal function. Based on final model parameter estimates, effects of the tested covariates are not expected to result in clinically relevant changes in upadacitinib steady-state exposures.

The multi-component modified nonlinear Schrödinger system with nonzero boundary conditions

In a previous paper (Matsuno 2011 J. Phys. A: Math. Theor. 44 495202), we have presented a determinantal expression of the bright N-soliton solution for a multi-component modified nonlinear Schrödinger (NLS) system with zero boundary conditions. The present paper provides the dark N-soliton solution for the same system of equations with plane-wave boundary conditions, as well as the bright-dark N-soliton solution with mixed zero and plane-wave boundary conditions. The proof of the N-soliton solutions is performed by means of an elementary theory of determinants in which Jacobi’s identity plays the central role. The N-soliton formulas obtained here include as special cases the existing soliton solutions of the NLS and derivative NLS equations and their integrable multi-component analogs. The new features of soliton solutions are discussed. In particular, it is shown that the N constraints must be imposed on the amplitude parameters of solitons in constructing the dark N-soliton solution with plane-wave boundary conditions. This makes it difficult to analyze the solutions as the number of components increases. For mixed type boundary conditions, the structure of soliton solutions is found to be more explicit than that of dark soliton solutions since no constraints are imposed on the soliton parameters. Last, we comment on an integrable multi-component system associated with the first negative flow of the multi-component derivative NLS hierarchy.

Kinetics of the reduction of μ–oxo–tetrakis(1, 10–phenanthroline) diiron (iii) complex by thiourea in aqueous phenanthrolinium buffer

The homovalent oxo-bridged binuclear iron(III) complex ion [Fe 2 O(phen) 4 Cl 2 ] 4+ (phen = 1, 10–phenanthroline) aquates to [Fe 2 O(phen) 4 (H 2 O) 2 ] 4+ in aqueous phenanthrolinium buffer solution (pH 3.25–4.50). The reaction of [Fe 2 O 2 (phen) 4 (H 2 O) 2 ] 4+ with thiourea in this buffer solution to give [Fe(phen) 3 ] 2+ , sulphite ion and urea was studied spectrophotometrically at 510 nm and found to be first order in [Fe 2 O 2 (phen) 4 (H 2 O) 2 ] 4+ and of mixed zero and first order in thiourea, i.e. reaction order with respect to thiourea varies from one to zero on increasing the thiourea concentration from 1.0–7.0 × 10 -2 mol dm -3 . The reaction is characterized by adduct formation. Changes in pH from 3.25 to 4.50 and ionic strength from 0.10 moldm -3 to 0.60 moldm -3 of the reaction solution were found to have no effect on the reaction rate. Catalysis and retardation were observed with the addition of Mg 2+ and CH 3 COO - ions respectively. A plausible mechanism consistent with the results obtained is proposed. Keywords: kinetics, mechanism, oxo-bridged, phenanthrolinium buffer, thiourea

Evaluation of Omeprazole Limited Sampling Strategies to Estimate Constitutive Cytochrome P450 2C19 Activity in Healthy Adults.

Limited sampling strategy (LSS) is a validated method to estimate pharmacokinetic (PK) parameters from a reduced number of samples. Omeprazole is used to phenotype in vivo cytochrome P450 (CYP) 2C19 activity. This study examined an LSS using 2 estimation methods to determine apparent oral clearance (CL/F) and thus CYP2C19 activity. Data from 7 previously published studies included healthy subjects receiving a single, oral dose of omeprazole with intensive PK sampling. CL/F was estimated using noncompartmental analysis (NCA) and population PK modeling. LSS was simulated by selecting the 1, 2, 4, and/or 6-hour postdose time points. Linear regression was performed to assess whether CL/F estimated from limited sampling could accurately predict CL/F from the full PK profile. Median CL/F was 23.7 L/h by NCA and 19.3 L/h by population PK modeling. In comparing the LSS NCA estimated versus observed CL/F, all evaluated linear regression models had unacceptable coefficients of determination (r, range: 0.14-0.81). With the population PK approach, 737 plasma concentrations (n = 71) and CYP2C19 genotype data were described with a 1-compartment structural model with mixed zero and first-order absorption and lag time. In comparing the population PK LSS estimated versus observed CL/F, all evaluated linear regression models had unacceptable r (range: 0.02-0.74). Post hoc comparison of CYP2C19 poor metabolizers versus CYP2C19 extensive metabolizers resulted in significantly lower CL/F in poor metabolizers versus extensive metabolizers. Omeprazole LSS performed poorly in estimating CL/F using 2 separate estimation approaches and does not seem to be a suitable method for determining CYP2C19 activity.

Pharmacokinetic Modeling and Simulation Analysis of LCB01-0371, A New Oxazolidinone Antibiotic Under Clinical Development

LCB01-0371, a new oxazolidinone with cyclic amidrazone under clinical development, has been shown to have a superior animal safety profile and better efficacy than those of linezolid. It works by binding to the 23S ribosomal RNA of the 50S subunit, thereby preventing the formation of the 70S initiation complex and inhibiting protein synthesis. The aims of this study were to develop a population pharmacokinetics (PPK) model for oral LCB01-0371 in healthy Korean volunteers and to predict the plasma LCB01-0371 concentration over time on various dosing regimens of LCB01-0371 via Monte-Carlo simulation Pharmacokinetics (PK) data were collected from 110 healthy, Korean, male subjects in three Phase 1 studies for LCB01-0371. LCB01-0371 was administered at single or multiple oral doses of 50 ~ 3,200 mg, and blood and urine samples were collected serially for PK. Plasma and urine concentrations of LCB01-0371 were measured by validated LC/MS-MS. PPK analysis were performed using nonlinear mixed effect modeling software NONMEM (version 7.3) with the first-order conditional estimation with interaction (FOCE-I) method. Plasma LCB01-0371 was absorbed fast after oral administration with followed by rapid decline in plasma concentration. The LCB01-0371 concentration in plasma and amount excreted in urine over time were best described by two-compartment model (central Vd, 82.4 L; peripheral Vd, 8.59 L) with absorption lag (ALAG1, 0.212 hour) and mixed zero (D1, 0.286 hour) and first order absorption (Ka, 80.7 /hour) process. Basic goodness of fit plots, visual predictive check plots exhibited that the final plasma and urine PPK model describe the data reasonably well. The current modeling and simulation analysis adequately characterized the pharmacokinetics of LCB01-0371 in Korean healthy adult male subjects, which will be a valuable tool in the search for the optimal dosing regimens of LCB01-0371.

The direct summand conjecture for some bigenerated extensions and an asymptotic version of Koh’s conjecture

This article deals with two different problems in commutative algebra. In the first part we give a proof of the direct summand conjecture for module-finite extension rings of mixed characteristic $$R\subset S$$ satisfying the following hypotheses: the base ring R is a unique factorization domain of mixed characteristic zero. We assume that S is generated by two elements which satisfy, either radical quadratic equations, or general quadratic equations under certain arithmetical restrictions. In the second part of this article we discuss an asymptotic version of Koh’s conjecture. We give a model theoretical proof using “non-standard methods”.

Population Pharmacokinetic Analysis of Simvastatin and its Active Metabolite with the Characterization of Atypical Complex Absorption Kinetics

The pharmacokinetics of simvastatin is complex with multiple peaks in the absorption phase, which cannot be adequately described by a conventional first order absorption model. The biotransformation of simvastatin into simvastatin acid, an active metabolite, is reversible. This study evaluated the pharmacokinetics of simvastatin and simvastatin acid, focusing on the absorption kinetics. Data were collected from three bioequivalence studies, in which subjects were administered 60 mg simvastatin, and from one crossover study, in which subjects were administered two doses randomly selected from 10, 20, 30, 40 to 80 mg simvastatin with washout period. The pharmacokinetics of simvastatin was assessed in 133 healthy males. Plasma concentrations of simvastatin and simvastatin acid were measured in 2,182 and 2,130 samples, respectively, and the pharmacokinetic data were analyzed using NONMEM. The time course of changes in the plasma simvastatin concentration was best described by a two-compartment linear model with three parallel absorption processes, each of which consisted of mixed zero-and first order absorption. Additions of inter-occasional variability to the absorption parameters significantly improved the model's fit. The disposition parameter estimates were significantly different when different absorption models were applied, indicating the importance of the appropriate absorption modeling. Pharmacokinetic modeling preferred the inter-conversion between simvastatin and simvastatin acid. A pharmacokinetic model describing the complex, multiple peak, absorption kinetics of simvastatin was formulated using three parallel, mixed zero and first-order absorptions. This type of absorption model may be applicable to other drugs that show irregular, multiple-peak concentrations during their absorption phase.

A Population Pharmacokinetic Analysis of Fimasartan, a Selective Angiotensin II Receptor Antagonist, in Healthy Caucasian Subjects and Korean Patients With Hypertension.

A population pharmacokinetic (PK) model of fimasartan, a selective angiotensin II receptor antagonist, was developed and significant covariates for its PK parameters were identified using 1438 plasma concentrations from 69 subjects (aged 19-64 years, weighing 43.5-95.3 kg), enrolled in 2 phase I studies (n = 42, 96.4% Caucasian) and a phase II study (n = 27, Korean hypertensive patients). The nonlinear mixed-effects analysis method by NONMEM was used, and the final model was qualified using sensitivity analysis, bootstrapping, and visual predictive checks. A two-compartment open linear PK model with mixed zero- and lagged first-order absorption best described observed plasma fimasartan concentrations. The typical value of the apparent clearance of fimasartan for those weighing 70 kg with total bilirubin of 0.7 mg/dL was 176 L/h (95% confidence interval: 163-189 L/h), and its interindividual and interoccasion variability as coefficient of variation was 26.9% (20.5-31.6%) and 10.5% (6.3-15.5%), respectively. Simulation of steady state concentrations indicated body weight was the most influential covariate on the exposure of fimasartan (i.e., lower level in heavier subjects). The population PK model of fimasartan should be refined as more studies are conducted in various clinical conditions.

On a mixed zero–one separable non-linear approach for water irrigation scheduling

We present a mixed zero–one separable non-linear approach to the optimization of the management of water resources used for agricultural irrigation purposes. It provides dynamic planning of the daily irrigation scheduling for a given land area by considering the irrigation network topography, water flow conditions and logistical operation constraints in order to optimize the use of water stored in a reservoir. We present a mixed zero–one separable non-linear program and a solution procedure that iteratively solves a mixed zero–one linear approximation of the model. We are not aware of any previous attempt to solve large-scale mixed zero–one separable non-linear programs of this kind. Some computational experiences on a large-scale real-life problem are reported.

Two hybrid meta-heuristics for the finite horizon ELSP in flexible flow lines with unrelated parallel machines

This article addresses the economic lot sizing and scheduling problem in flexible flow lines with unrelated parallel machines over a finite planning horizon. The objective is determination of a cyclic schedule that minimizes the sum of setup and inventory holding costs per unit time without any stock-out. A new mixed zero–one nonlinear mathematical programming has been developed for the problem. Due to difficulty of obtaining the optimal solution especially for medium and large-sized problems, we have also proposed two algorithms: a hybrid genetic algorithm (HGA) and a simulated annealing (SA). Two efficient constructive heuristic algorithms have been also proposed that provide some initial solutions for the algorithms. Moreover, a new local search approach has been proposed to improve solution quality of algorithms. The two proposed solution methods are compared on 180 randomly generated problems. Computational results indicate the superiority of the proposed HGA in compare to the SA with respect to the solution quality, but the proposed SA outperforms the proposed HGA with respect to the required computations time.

Functional Half-Life is a Meaningful??Descriptor of Steady-State??Pharmacokinetics of??an??Extended-Release Formulation of??a??Rapidly Cleared Drug

For many drugs, steady-state concentration-time profiles are often not optimally characterised by the intrinsic terminal elimination half-life for various reasons, including multiexponential disposition with minimal contribution of the terminal phase to steady-state exposure or use of controlled-release formulations with extended zero- or mixed zero-/first-order absorption. In such cases, 'effective' or 'functional' half-life (t((1/2)F)) has often been used to characterise steady-state pharmacokinetics. Valproic acid, commonly used in neuropsychiatry, has an elimination half-life of 4-16 hours in different populations (children vs adults, enzyme-induced vs uninduced). Divalproex-ER, a once-daily extended- release divalproex sodium formulation, is designed to release valproic acid over >18 hours. Hence the steady-state divalproex-ER concentration-time profiles have small peak-trough fluctuations that are not optimally characterised by valproic acid elimination half-life. In this study, the value of t((1/2)F) was calculated to characterise divalproex-ER steady-state concentration-time profiles. The value of t((1/2)F), defined as the time taken for the concentration to drop by one-half during a dosing interval (tau) at steady state, was derived using steady-state maximum (C(max)) and minimum (C(min)) plasma concentration and tau values, and calculated as ln(2)/(ln [C(max)/C(min)]/tau). The t((1/2)F) values of valproic acid in adult hepatic enzyme-uninduced healthy subjects and enzyme-induced epilepsy patients were calculated from five pharmacokinetic studies in which divalproex-ER was administered once daily for 6-14 days. The estimated geometric mean t((1/2)F) in uninduced adults was 40.0 hours versus the expected elimination half-life of 12-16 hours in this population (including patients on valproic acid monotherapy); for induced patients, t((1/2)F) was 26.9 hours versus the expected elimination half-life of 6-12 hours. The t((1/2)F) of valproic acid optimally characterises the expected steady-state C(max) to C(min )decrease of 33% in uninduced and 45% in induced adults following once-daily administration of divalproex-ER.

A co-operative parallel heuristic for mixed zero–one linear programming: Combining simulated annealing with branch and bound

This paper considers the exact approach of branch and bound (B&B) and the metaheuristic known as simulated annealing (SA) for processing integer programs (IP). We extend an existing SA implementation (GPSIMAN) for pure zero–one integer programs (PZIP) to process a wider class of IP models, namely mixed zero–one integer programs (MZIP). The extensions are based on depth-first B&B searches at different points within the SA framework. We refer to the resultant SA implementation as MIPSA. Furthermore, we have exploited the use of parallel computers by designing a co-operative parallel heuristic whereby concurrent executions of B&B and MIPSA, linked through a parallel computer, exchange information in order to influence their searches. Results reported for a wide range of models taken from a library of MIP benchmarks demonstrate the effectiveness of using a parallel computing approach which combines B&B with SA.

An electron paramagnetic resonance study of PP and PP/SBS blends irradiated with gamma rays

Electron paramagnetic resonance (EPR) measurements of Polypropylene (PP) and its blends with a Styrene–Butadiene–Styrene (SBS) copolymer in 10, 20, 30 and 40 wt.% of SBS were carried out. The samples were irradiated in the 0⩽D⩽100 kGy range at a dose rate of 4.8 kGy/h. Typical spectra indicative of the formation of peroxy and alkyl radicals were obtained. The dynamics of formation and recombination of radicals in these samples could be explained using a mixed zero and first order generation–recombination fit of the total spin concentration as a function of the integral dose. The time dependence of the spin concentration was studied assuming a mixed first order fit in the decay process. The parameters obtained from the fitting are interpreted in terms of the rate of formation of free radicals at the irradiation time and in terms of the decay time of the total free radical concentration.

Population pharmacokinetic-pharmacodynamic modelling of angiotensin receptor blockade in healthy volunteers.

To compare the pharmacokinetic and pharmacodynamic characteristics of angiotensin II receptor antagonists as a therapeutic class. Population pharmacokinetic-pharmacodynamic modelling study. The data of 14 phase I studies with 10 different drugs were analysed. A common population pharmacokinetic model (two compartments, mixed zero- and first-order absorption, two metabolite compartments) was applied to the 2685 drug and 900 metabolite concentration measurements. A standard nonlinear mixed effect modelling approach was used to estimate the drug-specific parameters and their variabilities. Similarly, a pharmacodynamic model was applied to the 7360 effect measurements, i.e. the decrease of peak blood pressure response to intravenous angiotensin challenge recorded by finger photoplethysmography. The concentration of drug and metabolite in an effect compartment was assumed to translate into receptor blockade [maximum effect (Emax) model with first-order link]. A general pharmacokinetic-pharmacodynamic (PK-PD) model for angiotensin antagonism in healthy individuals was successfully built up for the 10 drugs studied. Representatives of this class share different pharmacokinetic and pharmacodynamic profiles. Their effects on blood pressure are dose-dependent, but the time course of the effect varies between the drugs. The characterisation of PK-PD relationships for these drugs gives the opportunity to optimise therapeutic regimens and to suggest dosage adjustments in specific conditions. Such a model can be used to further refine the use of this class of drugs.

MATHEMATICAL MODELLING OF ETHANOL METABOLISM IN NORMAL SUBJECTS AND CHRONIC ALCOHOL MISUSERS

The time course of ethanol disappearance from the blood has been examined in normal males and females and in alcohol misusers. Blood alcohol estimations were made over a period of 3 hr, following an oral dose of ethanol (0.8 g/kg body weight) administered in the form of whisky. Attempts were made to fit the data to zero order, first order and mixed zero + first order kinetics. In the majority (75%) of normal females the blood ethanol concentrations was still increasing at 30 min. This was only seen in 50% of normal males and in 50% of non-dependent alcohol misusers, but not in dependent alcohol misusers. In all of the normal females the disappearance of ethanol could be adequately described by zero order kinetics. However, in the normal male group only 20% could be described by zero order kinetics, 10% fitted first order kinetics and the remainder required a mixed model of zero + first order. The rate constant for the zero order component of the control male group was identical to zero order rate constant obtained for the female control group. In the female alcohol misuser group, 40% of the curves could not be described by zero order kinetics and fitted best to a mixed model. The zero order component of the entire group was significantly increased (by 35%) compared to that obtained for the female control group. In the male dependent and non-dependent alcohol misuser groups, all blood alcohol concentration curves fitted best to mixed zero and first order kinetics.(ABSTRACT TRUNCATED AT 250 WORDS)

Membrane Reactor for Enzymic Deamidation of Food Proteins

ABSTRACTA soy protein hydrolysate was deamidated with peptidoglutaminase (PGase) retained within a 30kd spiral membrane. Reactor was operated at 30°C and 6.5 L/m2/hr flux in recycle mode to 60% conversion, then in diafiltration mode for 2 hr. Time course, predicted by a Michaelis‐Menten equation integrated for mixed zero‐ and first‐order kinetics with the corrections for the ultrafiltration (UF) interactions, matched that measured experimentally. The equation could be used to predict the potential activity and performance of PGase in UF reactors to achieve control of reactions for the optimal enzymic process. At the end of the run, 96% conversion and 99% of PGase were obtained. This method has the potential of being scaled‐up for the production of enzyme‐free deamidated proteins.