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PubMed1994

beta-Carotene supplementation results in an increased serum and colonic mucosal concentration of beta-carotene and a decrease in alpha-tocopherol concentration in patients with colonic neoplasia.

The aim of this study was to evaluate the colonic mucosal beta-carotene (BC) concentration following supplementation with BC and to determine if an increase in BC concentration influences vitamin E (alpha-tocopherol) status. The concentration of BC and alpha-tocopherol was assessed in serum and colonic tissue obtained from subjects with a history of colonic polyps or resected cancer (Dukes A, B1, or B2). Serum and mucosal biopsy samples were obtained prior to and following 3 months daily p.o. supplementation with 30 mg of BC or placebo. The concentration of BC was significantly increased in serum and colonic mucosa from both polyp and cancer subjects following supplementation as compared to presupplementation values and values from subjects receiving a placebo. The concentration of alpha-tocopherol in serum from cancer subjects was significantly decreased in samples obtained at the end of 3 months of BC supplementation as compared to placebo-matched controls. In BC-supplemented polyp subjects the tissue concentration of alpha-tocopherol was also significantly decreased relative to presupplementation values. The results indicate that BC supplementation does result in a significant accumulation of BC in the colonic mucosa but that the alpha-tocopherol concentration in both serum and colonic tissue may be compromised by an increased intake of BC. The mechanism for the decrease in alpha-tocopherol in conjunction with the increase in BC will require further study in order to develop strategies which will prevent vitamin E deficiency in BC-supplemented individuals.

Adult↗
PubMed1996

Postimplantation increase in plasma fibrinogen concentration with increase in relaxin concentration in pregnant dogs.

OBJECTIVE: To determine time courses of pregnancy-related changes in plasma fibrinogen, serum relaxin, and serum C-reactive protein-like immunoreactivity (CRP-LI) concentrations in pregnant and nonpregnant dogs. ANIMALS: 16 pregnant and 13 nonpregnant Beagles, 6 pregnant Beagles, and 3 pregnant and 3 nonpregnant dogs of other breeds. PROCEDURE: Fibrinogen was measured by nephelometric centrifugal analysis of light scatter in plasma samples of all dogs, and CRP-LI was measured by fluorescence immunoassay in selected sera from 10 pregnant and 10 nonpregnant dogs. Relaxin was measured in selected sera from 7 pregnant and 7 nonpregnant dogs. RESULTS: During pregnancy, fibrinogen concentration increased between days 21 and 30 after the luteinizing hormone surge, and was > 280 mg/dl between days 29 and 50 in 84 of 86 samples, with peak values 539 +/- 29 mg/ dl higher (P < 0.01) than those in nonpregnant dogs (188 +/- 8 mg/dl), higher values from days 21 to 50 (P < 0.01) than those in nonpregnant dogs, and values similar to those in nonpregnant dogs after day 50. Relaxin concentration was increased from days 26 to 30 and 0 to 4 days after fibrinogen concentration increased in pregnant dogs, and was not detectable in nonpregnant dogs. The CRP-LI concentration was higher in pregnant dogs at days 26 to 50, but values were inconsistent within and among dogs, and near the limit of sensitivity of the assay. CONCLUSIONS: Concentration of the acute-phase reactant protein fibrinogen increases after day 20 following implantation in dogs, at or just before the pregnancy-specific increase in relaxin concentration from days 26 to 30, and persists until day 50. CLINICAL RELEVANCE: Fibrinogen assay may be useful for pregnancy diagnosis in dogs.

Acute-Phase Proteins↗
PubMed1998

Evaluation of serum apolipoprotein C-III concentration by enzyme-linked immunosorbent assay and its higher concentration in cows during midlactation than during the nonlactating stage.

OBJECTIVE: To determine serum apolipoprotein C-III (apoC-III) concentration in cows in various stages of lactation by use of an ELISA. SAMPLE POPULATION: Sera obtained from 29 Holstein cows during early lactation, 65 cows during midlactation, 42 cows during late lactation, and 23 cows during the nonlactating stage. PROCEDURE: A 7.3-kd bovine apoC-III antiserum raised in rabbits was purified by affinity chromatography, and an ELISA was developed. RESULTS: In the immunoblot analysis, the antiserum reacted with the 7.3-kd apoC-III and moreover with another 8.2-kd apoC-III isoform. The 2 isoforms of apoC-III were also indistinguishable in the developed ELISA, the 2 proteins being measured as total apoC-III. In the ELISA for serum apoC-III concentration, addition of 2-mercaptoethanol to the coating buffer (50 mM sodium carbonate buffer, pH 9.6) was required. Mean+/-SEM bovine serum apoC-III concentration (microg/ml of serum) was 71.6+/-12.1 for the early lactating stage, 115+/-14.0 for the midlactating stage, 104+/-18.8 for the late lactating stage, and 55.3+/-8.4 for the nonlactating stage. Concentration of apoC-III was significantly (P < 0.05) higher in cows during midlactation than in cows during the nonlactating stage and was correlated negatively with serum triglyceride concentration (r = -0.479; P < 0.01) and positively with total cholesterol (r = 0.421; P< 0.05) and phospholipids (r= 0.415; P< 0.05) concentrations. CONCLUSIONS: Changes of apoC-III concentration in various stages of lactation suggest that this apolipoprotein is involved in a function related to lactation.

Animals↗
PubMed2000

Does a high concentration of calcium in the urine cause an important renal concentrating defect in human subjects?

The objective of this study was to evaluate the hypothesis that a high concentration of ionized calcium in the lumen of the medullary collecting duct causes an osmole-free water diuresis. The urine flow rate and osmolality were measured in normal human subjects, as well as in patients with a history of nephrolithiasis who excreted more than 5 mmol of calcium per 24 h. There was an inverse relationship between the concentration of calcium in the urine and the 24 h urine volume both in normal subjects and in patients with a history of nephrolithiasis. When the concentration of calcium in the urine was greater than 5 mmol/l, the urine volume was less than 1 litre per day in the majority of subjects. After 16 h of water deprivation, when the concentration of calcium in the urine was as high as 17 mmol/l (ionized calcium 7.4 mmol/l), urine osmolality was 1258 mOsm/kg of water and the urine flow rate was 0.30 ml/min. We conclude that, although a calcium receptor may be present in the lumen of the medullary collecting duct in human subjects, an extremely high concentration of urinary total and ionized calcium does not cause a clinically important defect in the renal concentrating process.

Adolescent↗
PubMed1982

The effect of dialysate sodium concentration on body fluid compartment volume, plasma renin activity and plasma aldosterone concentration in chronic hemodialysis patients.

Six stable chronic hemodialysis patients received six hemodialysis treatments: two each with the dialysate sodium concentration (DNa) 7% greater than serum sodium concentration, two with a DNa equal to serum sodium concentration and two with the DNa 7% less than the serum sodium concentration. During one treatment with each dialysate 2 kg of fluid was removed and during the other treatments the patient's weight was kept constant. Total body water (TBW), intracellular water (ICW), extracellular water (ECW), plasma volume (PV), plasma renin activity (PRA), aldosterone (ALDO), Na, BUN and osmolality were determined before and after each treatment. Fluid removal during dialysis had no effect on ICW with essentially all the fluid removed during dialysis coming from ECW. ICW increased with low DNa and decreased with high DNa. The effect of DNa on ECW and PV was the opposite of that on ICW. PRA increased and ALDO decreased during dialysis. Predialysis ALDO directly correlated with PRA (r = 0.68, p less than 0.001) but not with serum potassium concentration. Post dialysis ALDO was not significantly correlated with either PRA or potassium. Fluid removal and low DNa increased both PRA and ALDO. These studies indicate that water shifts from the extracellular space into intracellular space when DNa is lower than serum Na and the reverse is true when DNa exceeds serum Na. Plasma aldosterone decreases during dialysis despite an increase in PRA, possibly related to the decrease in serum potassium concentration. The effect of fluid removal and low DNa on PRA and ALDO may be related to a reduction in ECW and/or PV.

Adult↗
PubMed2001

Simultaneous determination of total and free drug plasma concentrations combined with batch-wise pH-adjustment for the free concentration determinations.

Batch-wise pH-adjustment of plasma samples for free concentration determinations can be performed directly in the ultrafiltration devices using a CO(2) incubator. The pH of the samples could be adjusted to within a sufficiently narrow interval though the initial differences in pH were large. The possibilities for simultaneous determination of free and total concentrations were studied using NAD-299 as a model compound. By adding a known concentration of a (13)C-labelled isotope of the studied drug to the sample prior to ultrafiltration it was possible to calculate the total concentration from the ratio of the drug peak area to the isotope peak area while the free concentration was calculated from the drug peak area. Initial experiments showed good precision and accuracy as well as a good correlation with concentration data acquired in the conventional way.

Chromatography, Liquid↗
PubMed2003

Influence of different concentrations of disodium fumarate on methane production and fermentation of concentrate feeds by rumen micro-organisms in vitro.

Batch cultures of mixed rumen micro-organisms were used to study the effects of different concentrations of disodium fumarate on the fermentation of five concentrate feeds (maize, barley, wheat, sorghum and cassava meal). Rumen contents were collected from four Merino sheep fed lucerne hay ad libitum and supplemented with 300 g concentrate/d. Disodium fumarate was added to the incubation bottles to achieve final concentrations of 0, 4, 7 and 10 mM-fumarate. In 17 h incubations, the final pH and total volatile fatty acid production increased (P<0.001) linearly for all substrates as fumarate concentration increased from 0 to 10 mm. Propionate and acetate production increased (P<0.05), while the value of the acetate:propionate ratio decreased (P<0.05) linearly with increasing doses of fumarate. In contrast, l-lactate and NH3-N concentrations in the cultures were not affected (P>0.05) by the addition of fumarate. For all substrates, fumarate treatment decreased (P<0.05) CH4 production, the mean values of the decrease being 2.3, 3.8 and 4.8 % for concentrations of 4, 7 and 10 mM-fumarate respectively. Addition of fumarate did not affect (P>0.05) the total gas production. If the results of the present experiment are confirmed in vivo, fumarate could be used as a feed additive for ruminant animals fed high proportions of cereal grains, because it increased pH, acetate and propionate production and it decreased CH4 production.

Acetates↗
PubMed2004

High radioactive concentration of 99mTc from a zirconium [99Mo]molybdate gel generator using an acidic alumina column for purification and concentration.

BACKGROUND: Newer applications of radiopharmaceuticals in nuclear medicine require pertechnetate of moderate to high radioactive concentration. Hence there is a need to develop simple procedures for the concentration of pertechnetate, and such a procedure is given in this paper. METHODS: Ten to 20 ml of sodium [Tc]pertechnetate eluted in de-ionized water from a zirconium [Mo]molybdate (ZrMo) gel column generator was passed through 2 g of an acidic alumina bed (35 x 8 mm) in order to remove the co-eluted traces of Mo and to retain the pertechnetate. The retained pertechnetate was then re-eluted, quantitatively, in 3 ml of normal saline, from the alumina column. RESULTS: About a 4-fold increase in radioactive concentration of Tc was obtained (cf. approximately 10-12 ml normal saline is required for the elution of Tc from the gel column). Generators containing up to 22.2 GBq (600 mCi) Mo in 6-7 g ZrMo gel column (35 x 13 mm) were prepared and a radioactive concentration of Tc up to 4 GBq x ml (110 mCi x ml) was obtained on the first day of use. The overall recovery of Tc was >90%, Mo breakthrough was 10 to 10% and the duration of concentration was 3-5 min. The chemical impurity in terms of Al, Mo and Zr was <10 ppm each. The same procedure for the concentration of pertechnetate was applied to generators with 12-15 g ZrMo gel beds to obtain a higher capacity Tc gel generator, with similar findings.

Aluminum Oxide↗
PubMed1980

Effect of urea concentration of pelvic fluid on renal concentrating ability.

The role of the pelvic urine in the renal concentration process was examined in anesthetized antidiuretic rats. The left ureter was cannulated with perfusion and collection catheters so that the composition of the fluid bathing the papilla could be altered by superperfusing solution of known composition without opening the renal pelvis, exposing the papilla, or altering intrapelvic pressure. The effect on urinary osmotic pressure (Uosmol) of papillary superperfusion with solutions of varying urea concentrations and total osmolality was examined. Papillary superperfusion with solutions containing no urea or less urea than preperfusion pelvic urine caused marked reductions in Uosmol regardless of the osmotic pressure of the solution. Superperfusion solutions with urea concentrations similar to that of preperfusion pelvic urine but lower in osmotic pressure than preperfusion urine produced no change in Uosmol. Superperfusion solutions with urea concentrations higher than that of preperfusion urine and with osmotic pressure equal to that of the preperfusion urine increased Uosmol. Finally, superperfusion of the papilla with urea solutions of greater than 2,370 mosmol/kg H2O and hypertonic to preperfusion urine decreased Uosmol. We conclude that the urea concentration of the pelvic urine plays an essential role in the urinary concentration mechanism.

Animals↗
PubMed2002

IFCC primary reference procedures for the measurement of catalytic activity concentrations of enzymes at 37 degrees C. Part 2. Reference procedure for the measurement of catalytic concentration of creatine kinase.

This paper is the second in a series dealing with reference procedures for the measurement of catalytic activity concentrations of enzymes at 37 degrees C and the certification of reference preparations. Other parts deal with: Part 1. The Concept of Reference Procedures for the Measurement of Catalytic Activity Concentrations of Enzymes; Part 3. Reference Procedure for the Measurement of Catalytic Concentration of Lactate Dehydrogenase; Part 4. Reference Procedure for the Measurement of Catalytic Concentration of Alanine Aminotransferase; Part 5. Reference Procedure for the Measurement of Catalytic Concentration of Aspartate Aminotransferase; Part 6. Reference Procedure for the Measurement of Catalytic Concentration of gamma-Glutamyltransferase; Part 7. Certification of Four Reference Materials for the Determination of Enzymatic Activity of gamma-Glutamyltransferase, Lactate Dehydrogenase, Alanine Aminotransferase and Creatine Kinase at 37 degrees C. A document describing the determination of preliminary reference values is also in preparation. The pro- described 30 degrees C IFCC reference method (1). Differences are tabulated and commented on in Appendix 3.

Body Temperature↗
PubMed2002

IFCC primary reference procedures for the measurement of catalytic activity concentrations of enzymes at 37 degrees C. Part 3. Reference procedure for the measurement of catalytic concentration of lactate dehydrogenase.

This paper is the third in a series dealing with reference procedures for the measurement of catalytic activity concentrations of enzymes at 37 degrees C and the certification of reference preparations. Other parts deal with: Part 1. The Concept of Reference Procedures for the Measurement of Catalytic Activity Concentrations of Enzymes; Part 2. Reference Procedure for the Measurement of Catalytic Concentration of Creatine Kinase; Part 4. Reference Procedure for the Measurement of Catalytic Concentration of Alanine Aminotransferase; Part 5. Reference Procedure for the Measurement of Catalytic Concentration of Aspartate Aminotransferase; Part 6. Reference Procedure for the Measurement of Catalytic Concentration of gamma-Glutamyltransferase; Part 7. Certification of Four Reference Materials tamyltransferase, Lactate Dehydrogenase, Alanine Aminotransferase and Creatine Kinase at 37 degrees C. A document describing the determination of preliminary upper reference limits is also in preparation. The procedure described here is deduced from the previously described 30 degrees C IFCC reference method (1). Differences are tabulated and commented on in Appendix 1.

Body Temperature↗
PubMed2002

IFCC primary reference procedures for the measurement of catalytic activity concentrations of enzymes at 37 degrees C. International Federation of Clinical Chemistry and Laboratory Medicine. Part 4. Reference procedure for the measurement of catalytic concentration of alanine aminotransferase.

This paper is the fourth in a series dealing with reference procedures for the measurement of catalytic activity concentrations of enzymes at 37 degrees C and the certification of reference preparations. Other parts deal with: Part 1. The Concept of Reference Procedures for the Measurement of Catalytic Activity Concentrations of Enzymes; Part 2. Reference Procedure for the Measurement of Catalytic Concentration of Creatine Kinase; Part 3. Reference Procedure for the Measurement of Catalytic Concentration of Lactate Dehydrogenase; Part 5. Reference Procedure for the Measurement of Catalytic Concentration of Aspartate Aminotransferase; Part 6. Reference Procedure for the Measurement of Catalytic Concentration of Gamma-Glutamyltransferase; Part 7. Certification of Four Reference Materials for the Determination of Enzymatic Activity of Gamma-Glutamyltransferase, Lactate Dehydrogenase, Alanine Aminotransferase and Creatine Kinase at 37 degrees C. A document describing the determination of preliminary upper reference limits is also in preparation. The procedure described here is deduced from the previously described 30 degrees C IFCC reference method. Differences are tabulated and commented on in Appendix 2.

Alanine Transaminase↗
PubMed2002

IFCC primary reference procedures for the measurement of catalytic activity concentrations of enzymes at 37 degrees C. International Federation of Clinical Chemistry and Laboratory Medicine. Part 5. Reference procedure for the measurement of catalytic concentration of aspartate aminotransferase.

This paper is the fifth in a series dealing with reference procedures for the measurement of catalytic activity concentrations of enzymes at 37 degrees C and the certification of reference preparations. Other parts deal with: Part 1. The Concept of Reference Procedures for the Measurement of Catalytic Activity Concentrations of Enzymes; Part 2. Reference Procedure for the Measurement of Catalytic Concentration of Creatine Kinase; Part 3. Reference Procedure for the Measurement of Catalytic Concentration of Lactate Dehydrogenase; Part 4. Reference Procedure for the Measurement of Catalytic Concentration of Alanine Aminotransferase; Part 6. Reference Procedure for the Measurement of Catalytic Concentration of Gamma-Glutamyltransferase; Part 7. Certification of Four Reference Materials for the Determination of Enzymatic Activity of Gamma-Glutamyltransferase, Lactate Dehydrogenase, Alanine Aminotransferase and Creatine Kinase at 37 degrees C. A document describing the determination of preliminary upper reference limits is also in preparation. The procedure described here is deduced from the previously described 30 degrees C IFCC reference method. Differences are tabulated and commented on in Appendix 3.

Aspartate Aminotransferases↗
PubMed2002

IFCC primary reference procedures for the measurement of catalytic activity concentrations of enzymes at 37 degrees C. International Federation of Clinical Chemistry and Laboratory Medicine. Part 6. Reference procedure for the measurement of catalytic concentration of gamma-glutamyltransferase.

This paper is the sixth in a series dealing with reference procedures for the measurement of catalytic activity concentrations of enzymes at 37 degrees C and the certification of reference preparations. Other parts deal with: Part 1. The Concept of Reference Procedures for the Measurement of Catalytic Activity Concentrations of Enzymes; Part 2. Reference Procedure for the Measurement of Catalytic Concentration of Creatine Kinase; Part 3. Reference Procedure for the Measurement of Catalytic Concentration of Lactate Dehydrogenase; Part 4. Reference Procedure for the Measurement of Catalytic Concentration of Alanine Aminotransferase; Part 5. Reference Procedure for the Measurement of Catalytic Concentration of Aspartate Aminotransferase; Part 7. Certification of Four Reference Materials for the Determination of Enzymatic Activity of Gamma-Glutamyltransferase, Lactate Dehydrogenase, Alanine Aminotransferase and Creatine Kinase at 37 degrees C A document describing the determination of preliminary upper reference limits is also in preparation. The procedure described here is deduced from the previously described 30 degrees C IFCC reference method. Differences are tabulated and commented on in Appendix 1.

Catalysis↗
PubMed2002

Concentrations of conjugated linoleic acid (cis-9, trans-11-octadecadienoic acid) are not increased in tissue lipids of cattle fed a high-concentrate diet supplemented with soybean oil.

Conjugated linoleic acid (CLA), a mixture of isomers of linoleic acid, has many beneficial effects, including decreased tumor growth in animal cancer models. The cis-9, trans-11 isomer of CLA (CLA9,11) can be formed in the rumen as an intermediate in biohydrogenation of linoleic acid. Recent data, however, indicate that tissue desaturation of trans-fatty acids is an important source of CLA9,11 in milk. Our objective was to determine whether supplementing a high-corn diet with soybean oil (SBO; a source of linoleic acid) would increase concentrations of CLA in ruminal contents and tissue lipids. Four ruminally cannulated steers were utilized in a Latin square design with 28-d periods. A control diet (80% cracked corn, 2.0% corn steep liquor, 8.0% ground corn cobs, and 10% supplement [soybean meal, ground shelled corn, minerals, and vitamins]) was supplemented with 2.5, 5.0, or 7.5% (DM basis) SBO. Supplemental SBO did not affect ruminal pH or concentrations of the major VFA. The proportion and amount (mg FA/g DM ruminal contents) of CLA9,11 were not increased by increasing dietary SBO. However, the proportion and amount of the trans-10, cis-12 CLA isomer (CLA10,12) in ruminal contents increased linearly (P < 0.006) as dietary SBO increased. Trans-18:1 isomers in ruminal contents increased linearly (P < 0.02) as dietary SBO increased. The proportion of CLA10,12 was correlated positively (P < 0.001) with proportions of trans-C 18:1 isomers in ruminal contents. Conversely, CLA9,11 was correlated negatively (P < 0.05) with the proportions of trans-18:1 in ruminal contents. The same high-corn diet, supplemented with 0 or 5% SBO, was fed to 20 Angus-Wagyu heifers for 102 d in a randomized complete block design to determine the effect of added SBO on tissue deposition of CLA. Supplemental SBO did not affect feed intake, gain:feed, or carcass quality. Tissue samples were obtained from the hindquarter, loin, forequarter, liver, large and small intestine, and subcutaneous, mesenteric, and perirenal adipose depots. The concentration of CLA9,11 was greatest in subcutaneous adipose tissue but was not affected in any tissue by SBO. Supplementing high-corn diets with SBO does not increase CLA9,11 concentrations in tissues of fattening heifers. Research is needed to identify regulatory factors for pathways of biohydrogenation that lead to increased concentrations of CLA10,12 in ruminal contents when high-oil, high-concentrate diets are fed.

Adipose Tissue↗
PubMed2005

Changes in ruminal fermentation and protein degradation in growing Holstein heifers from 80 to 250 kg fed high-concentrate diets with different forage-to-concentrate ratios.

Six Holstein heifers (initial BW = 65.2 +/- 1.8 kg) fitted with ruminal cannulas were used in a repeated measures trial to assess the effect of age and forage-to-concentrate ratio on ruminal fermentation end products and in situ degradation kinetics of four plant protein supplements (soybean meal, sunflower meal, peas, and lupin seeds). Alfalfa hay also was incubated in situ to estimate NDF degradation. Three experimental periods were conducted at 13, 27, and 41 wk of age. Heifers were fed one of two diets, 12:88 vs. 30:70 forage-to-concentrate ratio (DM basis), offered as total mixed ration on an ad libitum basis. Intakes of DM, OM, CP, NDF, and ADG were not affected (P > or = 0.105) by diet. The 30:70 diet resulted in faster (P = 0.045) fluid passage rate and decreased (P = 0.015) ammonia N concentration compared with the 12:88 diet, but no differences (P > or = 0.244) were detected in ruminal pH and total VFA concentration between diets. The rate of degradation and the effective degradability of N in protein supplements was greater with the 30:70 diet for peas (P < or = 0.008) and lupin seeds (P < or = 0.02), and in the 12:88 diet for sunflower meal (P < or = 0.06). Degradation of NDF of alfalfa hay was low with both diets (18.5 and 23.7 % for 12:88 and 30:70, respectively); however, the rate and extent of DM and NDF degradation were greater (P < or = 0.016) with the 30:70 diet, suggesting a higher cellulolytic activity. Total VFA concentration and the proportion of propionate increased (P < or = 0.035), and the acetate proportion decreased (P = 0.021) with age. Average pH, ammonia N concentration, and passage rates were not affected (P > or = 0.168) by age. Degradation rate and effective degradability of N of sunflower meal, peas, lupin seeds, and of DM of alfalfa hay increased (P < or = 0.08) with age, but degradation kinetics of NDF of alfalfa hay was not affected (P > or = 0.249). The increase in the rate and extent of N degradation with age would suggest an increase in proteolytic activity, and the changes in the fermentation pattern may reflect an increase in amylolytic activity caused mainly by an increase in the gross intake of nonstructural carbohydrates and by adaptation of ruminal microflora after long exposure to these nutrients.

Acetates↗
PubMed2001

Protein binding of glipizide using equilibrium dialysis technique: effects of hydrogen ion concentration, drug concentration and ionic strength.

The objective of this research was to investigate the effects of hydrogen ion concentration, drug concentration and ionic strength on the binding affinity of glipizide to albumin protein. Different buffer solutions of different pH values (pH 6.7, 7.5 and 8.5), different drug concentrations (2.45 mg, 4.82 mg and 9.42 mg), and phosphate buffer solutions pH 7.5 of different ionic strength (0.1, 0.4 and 1.0) were prepared. The effects of pH, drug concentration and ionic strength on the amount of glipizide bounded to 0.25 g bovine albumin was investigated. As the pH of the solution was increased from pH 6.4 to pH 8.5, milligrams drug bounded to gram protein (r value) decreased from 8.2 mg to 3.84 mg/g protein. Also as the ionic strength of the solution was increased from 0.1 to 1.0, the r value decreased from 10.76 mg to 3.96 mg/g protein. However, the r value did not change significantly with increasing of drug from 2.45 mg to 9.42 mg/25 ml. The r value was 7.36 mg/g protein when concentration of the drug was 2.45 mg/25 ml and 7.4 mg/g protein when the concentration of the drug was 9.42 mg/25 ml. This study demonstrated that factors such as high pH and high ionic strength can alter drug-protein binding and consequently increase free drug in plasma and increase bioavailability of slightly water insoluble drug such as antidiabetic drugs.

Dialysis↗