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PubMed1985

Protein binding and disposition of lignocaine in the elderly.

Single dose studies were performed in six young and six elderly nonsmokers using lignocaine as a model drug with high intrinsic clearance. Subjects received lignocaine 250 mg orally and 50 mg intravenously in random order and drug concentrations in blood and plasma were measured for up to 8 h after dose. Protein binding was estimated at 37 degrees C by equilibrium dialysis. Indocyanine green kinetics were also calculated in each individual following 0.15 mg/kg intravenously. Bioavailability of lignocaine was greater in the elderly but there was no apparent difference in the rate of absorption. Intrinsic clearance of lignocaine was lower in the aged. Elimination half-life was longer in the elderly but there was no significant difference in apparent volume of distribution or systemic clearance of lignocaine. Plasma clearance of indocyanine green showed no correlation with systemic lignocaine clearance and was lower in the aged subjects. Blood/plasma lignocaine ratio was less than unity in both groups. Binding of lignocaine to plasma proteins showed concentration-dependence and was higher in the geriatric group. Maximum binding capacity of lignocaine was greater in the elderly but the binding affinity did not significantly change with age. Greater oral bioavailability of drugs like lignocaine may produce higher plasma concentrations in the elderly. Unlike indocyanine green, the systemic clearance of lignocaine was unaltered by age in this group of non-smokers. The protein-binding of lignocaine, like many other basic drugs, is increased in elderly subjects.

Adult↗

PubMed1980

An evaluation of maprotiline intravenous kinetics and comparison of two oral doses.

The kinetics of maprotiline have been evaluated in six normal volunteers following rapid intravenous administration of 75 mg. Blood levels could be resolved using a biexponential equation. Mean estimates of half-life, volume of distribution and systemic clearance were 40 +/- 15 h, 51.7 +/- 18.01/kg and 0.92 +/- 0.24/kg/h, respectively. Blood/plasma concentrations varied between subjects from 0.77 to 1.64. A comparison of the bioavailability of two oral doses (a 75 mg tablet and three 25 mg tablets) was carried out in the same volunteers. No significant difference was observed between the maprotiline concentrations obtained for the two doses at sampling times up to 26 h. No significant difference was found in the area under the concentration vs. time curves for the two doses. Equivalent bioavailability can be assumed. On the basis of the intravenous injection study, systemic bioavailability averaged 66% and 70% for the 75 mg and three 25 mg tablets respectively.

Administration, Oral↗

PubMed1976

The pharmacokinetics of chlormethiazole following intravenous administration in the aged.

Eight healthy aged subjects were administered 1.2 g of chlormethiazole by constant-rate intravenous infusion. The disposition of the drug was found to be multi-exponential in character. Fits of plasma level-time data to two- and three-compartment open models were assessed with the aid of statistical tests. For three of the subjects the experimental data were adequately fitted to a two-compartment pharmakcokinetic model, however a three-compartment model was necessary to fit the data observed for a further four subjects. An anomalous chlormethiazole plasma concentration-time curve was obtained for the remaining subject. The disposition half-life of chlormethiazole was 8.49 +/- 3.28 h and the plasma clearance was 16.14 +/- 5.00 ml/min/kg. These values were significantly different to those reported earlier for young adult subjects and the clinical implications have been discussed. The blood/plasma concentration ratio of chlormethiazole was found to be approximately one with some evidence for concentration dependence.

Aged↗

PubMed1976

Comparison of the pharmacokinetics of diazepam after single and subchronic doses.

In seven healthy male volunteers the effects of the pattern of dosing on the pharmacokinetics of diazepam have been studied. A cross-over design was employed that consisted of three parts: a single intravenous dose (0.1 mg/kg), and oral dosing (10 mg/day) for six days followed by an intravenous bolus (0.1 mg/kg) on the seventh day, followed by re-examination of a single intravenous dose after diazepam (D) and its major metabolite desmethyldiazepam (DD) had been completely eliminated. Plasma levels of D and DD were monitored by a specific, sensitive GLC-method. In younger patients (n = 5, age 29 - 35 years) the elimination half-life, T1/2(beta), of D was 33.9 +/- 10.6 h (mean +/- S.D.) after the single dose. The control study gave an almost identical result (35.7 +/- 12.1). After subchronic dosage in all patients T1/2(beta) showed a modest but significant prolongation (paired t-test p less than 0.01) to 52.9 +/- 17.4 h. It was caused by a significant decrease (p = 0.016) in total plasma clearance (Cl), from 26.0 +/- 10.8 ml/min. Older patients (age 43-60 years) showed the same phenomenon. Blood/plasma ratios remained constant indicating no change in protein binding. Biliary excretion of D was measured in five patients with a T-tube. Only negligible amounts (0.3 - 0.4%) of administered D were excreted within 3 days after subchronic dosage, which demonstrates a lack of enterohepatic cycling of D. After multiple administration of D, there was accumulation of DD to levels approximately five times higher than after a single dose. The possibility that the slower elimination of D after subchronic treatment might be caused by DD was also supported by experiments in dogs and rabbits. After pretreating rabbits with DD and maintaining a high DD plasma level, there was prolongation of T1/2(beta) from 2.7 h to 5.2 h, with a corresponding decrease of Cl from 101.6 ml/min to 23.4 ml/min. Similar results were obtained in dogs. It is concluded that the disposition of D is altered by subchronic use and may be regulated by the plasma DD concentration.

Administration, Oral↗

PubMed1986

The pharmacokinetics after intravenous and oral administration in man of the alpha 2-adrenoreceptor antagonist idazoxan (RX781094).

A high performance liquid chromatographic method was developed for the quantitative determination of idazoxan in plasma. The assay was used to study the disposition of the drug after intravenous infusion and oral administration to five normal subjects. After i.v. administration the kinetics could be described by a two compartment model with a mean elimination half life of 4.20 h. The mean calculated volume of distribution during the elimination phase was 3.20 l/kg-1 and the mean plasma clearance was 824 ml min-1. After oral administration a lag period before onset of absorption was observed in all five volunteers, the plasma levels declining monoexponentially from the peak concentration with a mean elimination half life of 5.58 h. The absolute availability varied between 26% and 41% with a mean value of 34%. In-vitro measurements produced a blood/plasma ratio of 1.3 for idazoxan.

Administration, Oral↗

PubMed1989

Pharmacokinetic characterization of the antiarrhythmic drug diprafenone in man.

The pharmacokinetics of the antiarrhythmic drug diprafenone have been investigated in 6 healthy volunteers following single intravenous (50 mg) and oral doses (50 and 150 mg). Diprafenone was mainly eliminated by metabolism in the liver. Following i.v. infusion of 50 mg diprafenone, the terminal half-life of elimination was 1.50 h, the volume of distribution at steady-state was 1.23 l.kg-1, and the free fraction in plasma was 1.68%. Mean total plasma clearance was 741 ml.min-1.70 kg-1, which approaches normal liver blood flow after correction for the blood/plasma concentration ratio. Thus, diprafenone can be classified as a high extraction drug. Following oral administration, a dose-dependent increase in bioavailability from 10.9 (50 mg dose) to 32.5% (150 mg dose) was observed. The data suggest that diprafenone is subject to saturable hepatic first-pass metabolism.

Administration, Oral↗

PubMed1980

Clearance calculations in hemodialysis: application to blood, plasma, and dialysate measurements for ethambutol.

With the increasing use of artificial kidneys, numerous reports have appeared describing the pharmacokinetics of administered drugs in dialysis patients. Unfortunately, different investigators use different measures of dialysis clearance in reporting their results. Few studies have appeared in which actual measurements have been made in blood and dialysate as well as in plasma to experimentally show the variability of individual measurements and to demonstrate the inaccuracy of certain clearance measurements. We do so here, using the drug ethambutol. The effect of the artificial kidney on the removal of ethambutol was investigated in four uremic patients undergoing chronic hemadialysis. Ethambutol was administered by i.v. infusion over 30 min. Hemodialysis started at the end of drug infusion. Blood, plasma, and dialysate samples were collected periodically over 3 hr and analyzed for ethambutol content. Dialysis clearance was calculated by arterial-venous difference and by simultaneous dialysate measurement. The extraction efficiency of the hollow fiber dialyzers ranged from 36.2% to 43.8% in terms of blood and from 38.0% to 45.4% in terms of plasma. The mean clearance values due to dialysis were 108.08 and 88.1 ml/min measured with plasma and blood as body fluids of reference, respectively. Dialysis clearance calculated by dialysate measurement had a mean of 85.9 ml/min expressed as plasma and 74.7 ml/min expressed as blood. This study demonstrates that dialysis clearance when calculated using A-V difference and plasma flow is generally underestimated, particularly for a drug which extensively partitions into red blood cells. Ethambutol had a partition coefficient (blood/plasma) of greater than 1 in all four patients. The beta phase exhibited a mean half-life of approximately 2 hr on dialysis in comparison to off dialysis half-lives of 7 hr or longer in renal failure. Although ethambutol exhibits a markedly reduced half-life of the drug during hemodialysis, its recovery in the dialysis fluid during a 3-hr dialysis period constitutes only a small fraction of the dose administered.

Adult↗

PubMed2001

Pharmacokinetics of Gadomer-17, a new dendritic magnetic resonance contrast agent.

RATIONALE AND OBJECTIVES: Gadomer-17 is a new magnetic resonance (MR) contrast medium presently in clinical development. It is a dendritic gadolinium (Gd) chelate carrying 24 Gd ions. This study investigated the pharmacokinetic behavior of this contrast medium. METHODS: The pharmacokinetics of Gadomer-17 were investigated in different species (rat, rabbit, dog, monkey) for up to 7 days after intravenous (i.v.) injection of 25-100 micromol/kg body weight. In addition, elimination and biodistribution were evaluated after single i.v. injection of Gadomer-17 in rats. RESULTS: After i.v. injection Gadomer-17 distributes almost exclusively within the intravascular space without significant diffusion into the interstitial space. The volume of distribution (Vc) in the initial or alpha-phase ranged from 0.04 l/kg (rats, rabbits) to 0.06 l/kg (monkeys) and 0.07 l/kg (dogs), which reflects mainly the plasma volume. The blood/plasma concentration profile was found to be biphasic. The volume of distribution at a steady state is clearly smaller than that of other contrast media, which distribute to the extracellular space. After single i.v. injection in rats, the dendritic contrast medium was rapidly and completely eliminated from the body, mainly via glomerular filtration. No long-term accumulation or retention of the nonmetabolized agent was detectable in organs or tissues. CONCLUSIONS: Gadomer-17 is a promising new MR contrast medium that has an intravascular distribution and a rapid renal elimination.

Animals↗

PubMed1998

Ochratoxin A in food and feed: occurrence, legislation and mode of action.

Ochratoxins, of which ochratoxin A (OA) is the most prevalent, are secondary fungal metabolites of some toxigenic species of Aspergillus and Penicillium. OA has been shown to be nephrotoxic, hepatotoxic, teratogenic, carcinogenic and immunosuppressive. The natural occurrence of OA in food and feed stuffs is widespread, especially in temperate areas such as Canada, Denmark, Germany, Sweden and the United Kingdom, and detectable amounts were even found in randomly collected human milk samples in Germany, Sweden and Italy. Of greatest concern in humans is its implicated role in an irreversible and fatal kidney disease referred to as Balkan Endemic Nephropathy. The mean dietary intake for humans in the European Union was found to be in the range of 1 to 2 ng/kg bw/day. Compared with the Provisional Tolerable Daily Intake (PTDI) proposed by the WHO of 16 ng OA/kg bw/day for humans, the average OA intake in Europe seems to be rather low. The main contributor to the OA intake in humans are cereals and cereal products, other possible contributors are coffee, beer, pork, products containing pig blood/plasma, pulses and spices. Only very few countries have regulations for OA in food and feed products. Based on the current literature, the mechanisms involved in the toxicity of OA indicate three major effects: (1) inhibition of mitochondrial respiration correlated with a depletion of ATP; (2) inhibition of tRNA-synthetase accompanied by a reduced protein synthesis; and (3) enhanced lipid peroxidation. Generation of free radicals and lipid peroxidation as an important mode of action of OA in vitro and in vivo is discussed in detail, as well as counteracting effects of dietary antioxidants.

Aspergillus↗

PubMed2005

The 625G>A SCAD gene variant is common but not associated with increased C4-carnitine in newborn blood spots.

The 625G>A variant of the short-chain acyl-CoA dehydrogenase (SCAD) gene is considered to confer susceptibility for developing 'clinical SCAD deficiency' and appears to be common in the general population. To determine the frequency of the 625G>A variant in The Netherlands, we analysed 1036 screening cards of 5- to 8-day-old newborns and found 5.5% homozygous and 31.3% heterozygous for the 625G>A variant. An increased blood/plasma C4-carnitine concentration is considered to be one of the biochemical characteristics of SCAD deficiency. To explore the correlation of C4-carnitine levels with the 625G>A variant, we determined the C4-carnitine concentration, as well as the ratio of C4- to free carnitine, in blood spots from newborns, who were detected as homozygous, heterozygous or noncarriers for the gene variant. No significant differences were found between these groups. Our study demonstrates a high frequency of the 625G>A SCAD gene variant in the Dutch population, but no correlation to significantly increased C4-carnitine levels in blood spots taken between the 5th and 8th days of life. This latter observation might be the result of the relatively late timing of neonatal screening in our country, implying that fatty acid oxidation disorders may be missed at that stage. If the 625G>A variant is associated with clinical SCAD deficiency, the high frequency of the variant suggests a possible involvement of SCAD deficiency in the pathogenesis of common disorders, probably in relation to other genetic and/or environmental factors. However, homozygosity for the 625G>A variant might be only a biochemical phenomenon, representing a 'nondisease'.

Alleles↗

PubMed1983

Disposition of metals after portal and systemic administration to rats.

To determine if metals undergo significant hepatic presystemic elimination, male Sprague-Dawley rats were administered solutions of ionic 109Cd, 64Cu, 203Hg and CH3 203Hg, 210Pb, and 113Sn at 1.0 mumol metal/kg into either the ileocolic (portal administration) or femoral vein (systemic administration). Serial blood and bile samples were obtained for 90 min after administration. Whereas the area under the blood concentration vs time curve after portal administration was not less than that following systemic administration or any metal, route-dependent differences in distribution did occur. Portal, in comparison to systemic administration, resulted in a higher blood/plasma concentration ratio for mercury and lower ratio for lead. These data suggest that the liver may play a role in the distribution of these metals within the blood. In addition, the biliary excretion of mercury, methylmercury, cadmium, and lead was higher after portal than after systemic administration. These route-dependent differences in disposition suggest that some degree of hepatic presystemic elimination occurs for several metals.

Animals↗

PubMed2006

The role of whole blood in thrombin generation in contact with various titanium surfaces.

Understanding of the thrombotic response (activation of the intrinsic coagulation system followed by platelet activation) from blood components upon contact with a titanium dental implant is important and not fully understood. The aims of this study were to evaluate: (1) the thrombogenic response of whole blood, platelet-rich plasma (PRP) and platelet-poor plasma (PPP) in contact with a highly thrombogenic surface as titanium, (2) the thrombogenic response of clinically used surfaces as hydroxyapatite (HA), machined titanium (mTi), TiO2 grit-blasted titanium (TiOB) and fluoride ion-modified grit-blasted titanium (TiOB-F). An in vitro slide chamber model, furnished with heparin, was used in which whole blood, PRP or PPP came in contact with slides of the test surfaces. After incubation (60 min rotation at 22 rpm in a 37 degrees C water bath), blood/plasma was mixed with EDTA or citrate, further centrifuged at +4 degrees C (2200 g at 10 min). Finally, plasma was collected pending analysis. Whole blood in contact with Ti alloy resulted in the binding of platelets to the material surface and in the generation of thrombin-antithrombin (TAT) complexes. With whole blood TAT levels increased 1000-fold compared with PRP and PPP, in which both almost no increase of TAT could be detected. In addition, the platelet activation showed a similar pattern with a 15-fold higher release of beta-TG in whole blood. In the in vitro chamber model with the clinically relevant materials, the fluoride-modified surface (TiOB-F) showed pronounced TAT generation compared with TiOB, mTi and HA. Similar results were achieved for platelet consumption and activation markers of the intrinsic coagulation system. Taken together these results implicate first that whole blood is necessary for sufficient thrombin generation and platelet activation during placement of implants. Second, a fluoride ion modification seems to augment the thrombogenic properties of titanium.

Biocompatible Materials↗

PubMed2003

Two-center clinical evaluation of a new automated fluorometric immunoassay for the quantitative analysis of total betaeta-human chorionic gonadotropin.

OBJECTIVES: This study evaluated the quantitative total betahCG assay on the Stratus CS point-of-care instrument at two medical centers. DESIGN AND METHODS: Analytical sensitivity, linearity, within-run and total imprecision, interferences, dilution recovery, method comparison (Dimension RxL), comparison of matched heparinized whole blood and plasma samples, and determination of the normal reference interval were studied. RESULTS: Analytical sensitivity was <0.5 IU/L. The assay's linear range was 0 to 1250 IU/L; the clinical reportable range was up to 50,000 IU/L. Within-run imprecision (CV) at both low (<20 IU/L) and elevated (760 IU/L) betahCG concentrations were <4%. Total imprecision for three QC levels and two pools were <4%. Method comparison showed Stratus CS betahCG = 0.98 +/- 0.01* Dimension RxL hCG -0.11 +/- 2.69 (n = 136; r = 0.996; Sy/x = 27.7). Matched heparinized whole blood/plasma sample-comparison showed: whole blood = 1.05*Plasma + 0.37 +/- 1.29 (n = 41; r = 1.000; Sy/x = 7.57). Mean dilution recovery was 99% (range: 95% to 103%). None of the 52 drugs tested, lipemia, icterus, hemolysis, LH, FSH, TSH, hGH or prolactin represented a significant interference with the assay. Reference intervals were <0.5 IU/L for males (n = 123) and <3.0 IU/L for nonpregnant females (n = 120). CONCLUSIONS: The Stratus CS betahCG test offers the advantage of quantitative measurement of total betahCG in whole blood at the point of care and is suitable for clinical use.

Calibration↗

PubMed2004

Selective and sensitive liquid chromatographic assay of amodiaquine and desethylamodiaquine in whole blood spotted on filter paper.

We have developed a sensitive, selective and reproducible reversed-phase HPLC method with ultraviolet detection (340 nm) for the simultaneous quantification of amodiaquine (AQ) and its major metabolite, desethylamodiaquine (AQm) in a small volume (200 microl) of whole blood spotted on filter paper. The method involves liquid-liquid extraction with diethyl ether followed by elution from a reversed-phase phenyl column with an acidic (pH 2.8) mobile phase (25 mM KH2PO4-methanol; 80:20% (v/v) +1% (v/v) triethylamine). Calibration curves in spiked whole blood were linear from 100-2500 ng/ml (r2 > or = 0.99) for AQ and 200-2500 ng/ml (r2 > or = 0.99) for AQm. The limit of detection was 5 ng for AQ and 10 ng for AQm. The relative recovery at 150 ng/ml of AQ (n = 6) was 84.0% and at 300 ng/ml of AQm the relative recovery was 74.3%. The intra-assay coefficients of variation at 150, 600 and 2250 ng/ml of AQ and 300, 600 and 2250 ng/ml of AQm were 7.7, 8.9 and 6.2% (AQ) and 10.1, 5.4 and 3.9% (AQm), respectively. The inter-assay coefficient of variation at 150, 600 and 2250 ng/ml of AQ and 300, 600 and 2250 ng/ml of AQm were 5.2, 8.1 and 6.9% (AQ) and 3.3, 2.3 and 4.6% (AQm). There was no interference from other commonly used antimalarial and antipyretic drugs (chloroquine, quinine, sulfadoxine, pyrimethamine, artesunate, acetaminophen and salicylate). The method is particularly suitable for pharmacokinetic studies in settings where facilities for storing blood/plasma samples are not available.

Amodiaquine↗

PubMed2005

Strategies to assess systemic exposure of chemicals in subchronic/chronic diet and drinking water studies.

Strategies were developed for the estimation of systemically available daily doses of chemicals, diurnal variations in blood levels, and rough elimination rates in subchronic feeding/drinking water studies, utilizing a minimal number of blood samples. Systemic bioavailability of chemicals was determined by calculating area under the plasma concentration curve over 24 h (AUC-24 h) using complete sets of data (> or =5 data points) and also three, two, and one selected time points. The best predictions of AUC-24 h were made when three time points were used, corresponding to Cmax, a mid-morning sample, and C(min). These values were found to be 103 +/- 10% of the original AUC-24 h, with 13 out of 17 values ranging between 96 and 105% of the original. Calculation of AUC-24 h from two samples (Cmax and Cmin) or one mid-morning sample afforded slightly larger variations in the calculated AUC-24 h (69-136% of the actual). Following drinking water exposure, prediction of AUC-24 h using 3 time points (Cmax, mid-morning, and Cmin) was very close to actual values (80-100%) among mice, while values for rats were only 63% of the original due to less frequent drinking behavior of rats during the light cycle. Collection and analysis of 1-3 blood samples per dose may provide insight into dose-proportional or non-dose-proportional differences in systemic bioavailability, pointing towards saturation of absorption or elimination or some other phenomenon warranting further investigation. In addition, collection of the terminal blood samples from rats, which is usually conducted after 18 h of fasting, will be helpful in rough estimation of blood/plasma half-life of the compound. The amount of chemical(s) and/or metabolite(s) in excreta and their possible use as biomarkers in predicting the daily systemic exposure levels are also discussed. Determining these parameters in the early stages of testing will provide critical information to improve the appropriate design of other longer-term toxicity studies.

2,4-Dichlorophenoxyacetic Acid↗

PubMed1998

An improved biotonometric method for determination of haemoglobin oxygen equilibrium curves.

A new biotonometric method for the determination of haemoglobin oxygen equilibrium curves is described. The procedure is based on the mixing of an oxygen-consuming organism, the yeast cell (Saccharomyces cerevisiae), with an oxidized blood/plasma mixture. The yeast cell consumes oxygen at a uniform rate, thus reducing the partial pressure of oxygen in the mixture. This in turn induces the dissociation of oxygen in a characteristic manner. The study of the whole blood samples from 26 healthy volunteer subjects gave the following results: p50 = 3.63 kPa +/- 0.23 kPa (mean +/- 1 S.D.); Hill slope n = 2.44 +/- 0.16; and CO2 Bohr factor = -0.47 +/- 0.11. For the within-run imprecision the coefficients of variation for the different parameters were: p50 C.V. = 4.4%; Hill slope n C.V. = 4.7%; and CO2 Bohr factor C.V. = 19%. The determination can be carried out with simple equipment: a blood gas analyzer with a coupled recorder.

Adult↗

PubMed1997

Population pharmacokinetics of sirolimus in kidney transplant patients.

OBJECTIVE: To characterize the dose-related pharmacokinetics of the immunosuppressant agent sirolimus (formerly rapamycin) in kidney transplant patients by use of two-stage and nonlinear mixed-effect model population methods. METHODS: Patients (n = 36) from three centers (Germany, the United Kingdom, and Sweden) who received steady-state oral doses of cyclosporine (ciclosporin) were assessed after single oral administration of sirolimus at doses of 3, 5, 10, and 15 mg/m2. Plasma and whole blood sirolimus samples were analyzed by a high-performance liquid chromatographic/mass spectrophotometric method. Simultaneous fitting used biexponential functions with intercept/slope or clearance/volume terms, as well as first-order absorption (ka) and a lag-time. RESULTS: The nonlinear mixed-effect model method (P-Pharm) provided a better characterization of sirolimus kinetics, especially for the absorption and distribution phases where fewer data were available per patient. Sirolimus distribution between whole blood and plasma was concentration-independent, with a mean blood/plasma ratio (coefficient of variation) of 30.9 (48.5%). Elimination was not influenced by dose, as shown by estimates of the terminal half-life of 63 hours (27.5%) and apparent oral blood clearance of 8.9 L/hr (38.2%). Sirolimus distribution parameters were influenced by body weight and surface area. Sirolimus was rapidly absorbed, as shown by the absorption lag-time of 0.27 hour (35.1%), and ka of 2.77 hr-1 (48.4%). The concomitant administration of sirolimus and cyclosporine did not reveal any pharmacokinetic interactions. CONCLUSION: This report provides an initial population pharmacokinetics of sirolimus in kidney transplant recipients receiving cyclosporine concurrently. Sirolimus blood and plasma pharmacokinetics were biexponential and linear for doses from 3 to 15 mg/m2. No pharmacokinetic interaction was found between sirolimus and cyclosporine.

Adult↗

PubMed1999

Surface plasmon resonance (SPR) analysis of coagulation in whole blood with application in prothrombin time assay.

It is previously shown that surface plasmon resonance (SPR) can be used to study blood plasma coagulation. This work explores the use of this technique for the analysis of tissue factor induced coagulation, i.e. prothrombin time (PT) analysis, of whole blood and plasma. The reference method was nephelometry. The prothrombin time analysis by SPR was performed by mixing two volumes of blood/plasma, one volume of thromboplastin, and one volume of CaCl2 solution directly on a sensor surface. The measurements show good agreement between nephelometry and SPR plasma analysis and also between SPR plasma and whole blood analysis. The effect of anticoagulant treatment on the clotting times was significant both quantitatively and qualitatively. The impact on the SPR signal of different physiological events in the coagulation process is discussed, and tentative interpretations of the sensorgram features are given. The major advantage of the SPR method compared to nephelometry is the possibility to perform analysis on whole blood instead of plasma. In conclusion, SPR is a promising method for whole blood coagulation analysis.

Anticoagulants↗