bluuebunny/crossref_metadata_2025_split huggingface dataset:
Comparison of two enteric‐coated acetylsalicylic acid preparations by monitoring steady‐state levels of salicylic acid and its metabolites in plasma and urine
Authors: Edgar B. , Bogentoft C. , Lagerström P.‐O. 
Published: October 2006

AbstractIn a randomized three‐way crossover study, 12 healthy male volunteers were given multiple oral doses, i.e. 1·5 g b.i.d. for 7 days, of two different types of enteric‐coated acetylsalicylic acid (ASA) preparations, one being a conventional enteric‐coated tablet (ET) and the other enteric‐coated granules (EG) in a capsule; conventional ASA tablets were used as a reference. Plasma levels and excretion of salicylic acid and some of its metabolites were investigated under steady‐state conditions.Plasma salicylic acid (SA) and salicyluric acid (SUA) levels were determined using a liquid chromatographic method. Two separate analyses were done to quantitate the metabolites in urine. SA, SUA, and gentisic acid were each assayed by the method used for plasma. Total salicylate was also determined.There was no significant difference in urinary excretion of total salicylate between the three formulations. A diurnal variation in the excretion of SUA and SA in urine was found. The two enteric‐coated formulations provided significantly higher morning plasma concentrations than the conventional aspirin. The AUC was found to be significantly higher for ET than for the other two formulations. EG gave more uniform plasma levels during the studied 12‐h intervals and also less inter‐ and intra‐individual variations than ET, indicating that a b.i.d. regimen may be suitable for EG.
Comparison of the erythrocyte partitioning method with two classical methods for estimating free drug fraction in plasma
Authors: Trung A. Ho Ngoc‐Ta , Sirois G. , Dubé L. M. , McGilveray I. J. 
Published: October 2006

AbstractA modification of the erythrocyte partitioning method for the rapid estimation of plasma‐free drug fractions (fu) is described and applied to five basic drugs. In the procedure, which uses readily available clinical laboratory equipment, fu is calculated from measurements of durg partitioning between plasma and erythrocytes, and between buffer and erythrocytes. Results obtained are compared with those from equilibrium dialysis or ultrafiltration techniques for amitriptyline, imipramine, quinidine, lidocaine, and propranolol. For each drug, the mean value of fu obtained with the erythrocyte partitioning procedure was not found to be significantly different from that determined by one of the two other classical techniques. The erythrocyte partitioning method lead to reproducible (mean C.V. = 6·25) and precise values of fu when compared to the other methods; its clinical application to lidocain gave results which agreed with those obtained by equilibrium dialysis.
Acute tolerance development to the diuretic effect of furosemide in the rat
Authors: Hammarlund Margareta , Paalzow Lennart K. 
Published: October 2006

AbstractFurosemide was given to rats as five different i.v. bolus doses (2.5–100mg kg−1), or as an i.v. infusion to a steady‐state concentration in plasma of 14μg ml−1. The urinary furosemide excretion rate (ΔAe/Δt) and the diuretic effect (volume of urine) were measured. A parallel shift in the excretion—response curve was seen as a fivefold increase in (ΔAe/Δt)50 ((ΔAe/Δt) at half‐maximal effect) between the i.v. bolus doses from 2.5 to 40 mg kg−1. The slope factor did not change. During infusion, a decrease in efficiency to 20 per cent of the initial value was seen. These results are indicative of an acute tolerance development to the diuretic effect of furosemide. Some intrarenal feedback inhibition mechanism might be involved, as the extracellular fluid volume seems to be of great importance to the effect obtained. The resulting effect can be compared with the influence of a competitive antagonist.
Comparison of nonlinear pharmacokinetic parameters estimated from the sinusoidal perfusion and venous equilibrium models
Authors: Wagner John G. 
Published: October 2006

AbstractIt is shown that the intrinsic and steady‐state clearances and the values of Vm, and Km, of the Michaelis—Menten equation estimated via the sinusoidal perfusion model are different from the corresponding values estimated via the venous equilibration model. The liver blood flow rates estimated by two theories (from plasma data) are identical. The comparison was made using the single dose oral and intravenous and steady‐state oral plasma concentration—time data for verapamil in six subjects previously published.
Comparison of fitting methods for the analysis of plasma concentration‐time data resulting from constant rate intravenous infusion
Authors: Johnson Stephen L. , Mayersohn Michael 
Published: October 2006

AbstractPlasma concentration‐time data resulting from constant rate intravenous infusion may be analysed in two ways:

Samples may be collected both during and after infusion and fit to an infusion model.
Samples may be collected after infusion is complete and the data may be fit as an i.v. bolus.
The purpose of this study was to contrast these two fitting procedures in terms of the accuracy of the parameter values obtained. Concentration‐time data were computer‐generated with the introduction of random error to simulate the disposition profiles of two model drugs. The results of these simulations indicate that satisfactory values for area‐dependent parameters may be obtained without fitting data during the infusion phase. The exception to this is the apparent steady‐state volume whose values become less accurate with longer infusion times. The parameters most affected by ignoring data points in the infusion phase are the central volume of distribution, and the coefficient and disposition rate constant associated with the initial, rapid phase of disposition. The equation which describes the entire concentration‐time profile provides the most accurate parameter estimates of the model equation. In addition, we also describe the influence of the fitting method on the intercompartmental transfer rate constants.
Comparative physiological disposition of some anthraquinone glycosides and aglycones
Authors: Moreau J. P. , Moreau S. , Skinner S. 
Published: October 2006

AbstractThe in vitro microbial degradation and the urinary excretion and biliary secretion in rats of two anthraquinone glycosides (sennosides A and B) and four aglycones (sennidins A and B, rhein, and danthron) were studied using a high performance liquid chromatographic system with gradient elution and amperometric detection. Microbial degradation of sennosides A and B occurred almost exclusively in the presence of mice caecum inoculae and was associated with the release of sennidins A and B. Rhein and danthron were indiscriminately metabolized by bacteria sampled from all regions of mice intestine, whereas sennidins lacked stability in biological media. The fraction of the dose administered orally to rats and recovered as aglycones or as glucuronides in bile and urine after 48 hours was five times greater for rhein (15 per cent) and danthron (13.4 per cent) than for sennosides A (1.8 per cent) and B (2.8 per cent) excreted or secreted as sennidins. These results support the concept that anthraquinone glycosides are less likely to enter the systemic circulation and, thus, are able to exert their laxative effect at lower doses than aglycones.
Confidence intervals for multiple‐dose concentrations in the one‐compartment open model with rapid intravenous injection
Authors: Karpinski K. F. 
Published: October 2006

AbstractThe parameters in a multiple‐dose compartmental model can be estimated from plasma concentration observations after a single dose of drug. These estimates can be used to obtain confidence intervals for the multiple‐dose concentrations. However, since the models are non‐linear functions of the parameters, no exact confidence interval procedures are available. In this paper a conservative interval estimation procedure1 is applied to the one‐compartment open model with rapid intravenous injection. Also, extended tables required in the estimation procedure are provided.
Selective incorporation of asialofetuin into hepatocyte of rat
Authors: Aramaki Yukihiko , Inaba Asaichi , Tsuchiya Seishi 
Published: October 2006

AbstractThe disposition of asialofetuin was studied in the rat. The radioactivity of 3H‐asialofetuin administered intravenously disappeared rapidly from the blood. Asialofetuin was specifically and rapidly incorporated into the liver, and had no affinity toward other tissues such as the lung, spleen, heart, and kidney. Asialofetuin accumulated in the lysosomal and microsomal fractions of the rat liver cells immediately after administration, shifted to the low dense fraction (cytosol fraction) with the elapsing of time, and was possibly digested by lysosomes. The elimination of 3H‐asialofetuin from the liver was fast and the degradates excreted into the bile and urine represented 90 per cent of the dose administered by 180 min following administration. It was suggested that asialofetuin functions as a carrier of drugs to the liver, especially to hepatocytes.
Allopurinol: A comparative study of the bioavailability and effect on plasma uric acid of two products in tablet form
Authors: Nissen Poul , Pedersen Linda 
Published: October 2006

AbstractA comparative bioavailability study was carried out with two allopurinol products, i.e. Allopurinol tablets 100 mg, DAK, and Apurin® tablets 100 mg, Gea. Eleven healthy volunteers participated and were given a single dose of 200 mg of each product according to the cross‐over principle. The bioavailability was evaluated with respect to the maximum plasma concentration, the peak time, and the area under the plasma concentration‐time curve for allopurinol and the major metabolite oxipurinol. The elimination half‐life of oxipurinol was also estimated. None of the parameters showed statistically significant differences (p > 0.10) between the two products. Furthermore, the pharmacodynamic effect of the two products was examined with respect to the reduction of plasma uric acid within 24 hours after administration of 200 mg allopurinol. The two products did not differ significantly (p>0.10) in this respect. It is concluded that the two tablet products are bioequivalent.
Pharmacodynamics of acute intranasal administration of verapamil: Comparison with IV and oral administration
Authors: Arnold T. H. , Tackett R. L. , Vallner J. J. 
Published: October 2006

AbstractThe present study was conducted in order to examine the intranasal administration of verapamil and compare this route to oral and intravenous administration in a 3 way crossover protocol in five dogs. Unanesthetized, adult mongrel dogs were given verapamil intravenously (0.5 mg/kg), orally (2.5 mg/kg) and intranasally (0.75 mg/kg) with at least a 3–4 day washout period between each administration. Blood samples were collected over a 10 hour period and analyzed for verapamil using HPLC with fluorescence detection. A lead II ECG was monitored to determine the effects of verapamil on heart rate and P‐R interval. Following intravenous administration, verapamil was distributed according to a two compartment model. Bioavailability (corrected for dose and elimination rate constant) following intranasal administration (36% ± 7%) was approximately 3 fold that after oral administration (13% ± 3%). Absorption from the nasal cavity appeared instantaneous compared to an absorption half‐life of 50 ± 6 min after oral administration. All three routes of administration resulted in significant increases in heart rate and increases in the P‐R interval. Maximal P‐R interval prolongation occurred after peak plasma concentrations of verapamil. The results of this study suggest that the intranasal route is a viable alternative route of administration for verapamil.
Acetylsalicylic acid metabolites in blood and urine after plain and enteric‐coated tablets
Authors: Montgomery P. R. , Sitar D. S. 
Published: October 2006

AbstractAcetylsalicylic acid (ASA) was administered orally as a single dose to 7 healthy male volunteers as plain or enteric‐coated (EntrophenR) tablets using a crossover design. Blood and urine samples were collected and analysed for ASA metabolites by high performance liquid chromatography. Labile and stable glucuronide conjugates of salicylic acid (SA) were measured in urine after differential hydrolysis with glucuronidase. Plasma kinetic parameters for the ASA metabolites SA and salicyluric acid were not different for the 2 formulations, apart from the delayed appearance after the enteric‐coated tablets. Total urinary recovery, and recovery of salicyluric acid and the two SA glucuronides were not different, thus confirming the equivalent bioavailability and metabolite profile of the 2 ASA formulations.
Influence of dioctyl sodium sulfosuccinate on the absorption of tetracycline
Authors: Shah Vinod P. , Hunt John P. , Fairweather William R. , Prasad Vadlamani K. , Knapp Gene 
Published: October 2006

AbstractA pilot bioavailability study was carried out to evaluate the drug interaction and influence of dioctyl sodium sulfosuccinate (DS) on the absorption/bioavailability of tetracycline. Three tetracycline products—a fast dissolving capsule, a slow dissolving capsule and a suspension, were used in the study. DS was administered (a) 30 minutes before tetracycline administration; and (b) on −3, −2 and −1 day in the evening before tetracyline administration. Frequent urine samples were collected up to 48 hours and analyzed by a microbiological method. Although not statistically significant in this small study, the results suggest that there is a reduction in tetracycline bioavailability due to DS. The indiscriminate use of surface active agents to increase the dissolution rate of solid oral dosage forms in the belief that the resulting increased dissolution improves product bioavailability must be questioned.
Relationship between plasma propranolol concentration and dose in young, healthy volunteers
Authors: Dey Mike , Brisson Jerry , Davis Gloria , Enever Robin , Pray Kathryn , Zaim Beyhan , Dvornik Dushan 
Published: October 2006

AbstractThe relationship between dose and bioavailability of propranolol was determined in 12 healthy male subjects. The doses employed were 10, 40, 80 or 160 mg of propanolol HCI given three times daily for 4 days. Daily minimum plasma levels showed that there was no accumulation of the drug. In all subjects, non‐linear relationships were observed between peak plasma level, or area under the plasma concentration‐time curve, and dose. The between subject variation of these parameters was not dose related.
Use of a limited physiologic model to explain target organ toxicity of bupivacaine as a function of route of administration
Authors: Denson Donald D. , Thompson Gary A. , Coyle Dennis E. 
Published: October 2006

AbstractA physiologic model to describe bupivacaine uptake by and elimination from brain and heart was developed. Preliminary validation of the model was accomplished by comparing concentration data predicted by the model with those determined in rabbits. The model was modified to examine similarities and differences following intravenous and epidural administration of 150 mg of bupivacaine in humans. Simulations illustrated why rapid cardiovascular and central nervous system toxicity occurs following intravenous administration and is absent when an identical dose is administered epidurally. A slow continuous intravenous infusion of bupivacaine was simulated to examine the possibility that brain and heart concentrations would continue to accumulate reaching toxic concentrations in the absence of blood concentrations associated with bupivacaine toxicity.
The disposition of pyrimethamine base and pyrimethamine pamoate in the mouse: Effect of route of administration
Authors: Coleman M. D. , Mihaly G. W. , Edwards G. , Howells R. E. , Breckenridge A. M. 
Published: October 2006

AbstractWe have investigated the plasma pharmacokinetics and mass fate in mice, of pyrimethamine administered as either the base or as the poorly soluble pamoate salt, in each case by the intraperitoneal (i.p.) and subcutanous (s.c.) routes. Following the administration of pyrimethamine base (i.p. and s.c.) and pyrimethamine pamoate (i.p.), maximum measured plasma levels of pyrimethamine were attained within 1 h, before declining monoexponentially. There was no significant difference between these three groups in the clearance (0.29 ± 0.05, 0.30 ± 0.03, 0.26 ± 0.05 ml min−1), elimination half‐life (4.5 ± 0.5, 4.8 ± 0.8, 4.9 ± 0.5 h) and AUC (19.4 ± 4.4, 17.3 ± 2.2, 21.1 ± 4.4 μg. h ml−1).By contrast, after s.c. dosage of pyrimethamine pamoate, drug absorption was significantly delayed, maximum plasma levels being reached after 4h, these levels being approximately one‐third of those in the other three groups. Absorption was however complete, as the values for AUC and clearance were not significantly different from the other groups.The pattern of faecal and urinary elimination of 14C radioactivity was unaffected by either dose site or formulation of pyrimethamine. The majority of the dose (44.5–64.2 per cent) was eliminated in the faeces suggesting extensive biliary excretion. Localization of 14C radioactivity in the major organs was negligible in all groups. Following each dose, between 85 and 98 per cent of the dose was accounted for.These studies indicate that of the four treatment groups only pyrimethamine pamoate on s.c. administration demonstrates a sustained release action from the dose site. This effect is not accompanied by any differences in AUC, clearance, and rate of elimination, when compared with the base given i.p. and s.c., or the pamoate salt given i.p., the latter groups displaying no slow release characteristics.
Pharmacokinetics and bioavailability of the anti‐emetic agent bromopride
Authors: Brodie R. R. , Chasseaud L. F. , Darragh A. , Lambe R. F. , Rooney L. , Taylor T. 
Published: October 2006

AbstractThe pharmacokinetics of bromopride, an anti‐emetic agent chemically related to metoclopramide, has been investigated in normal human subjects. After intravenous bolus doses of 10 mg, a one‐compartment open model appeared adequate to describe the plasma drug concentration data. The systemic clearance of bromopride was 899 ml min−1 ± 22 per cent CV, the volume of distribution was 2151 ± 16 per cent CV, and the elimination half‐life was 2.9h ± 21 per cent CV. Over a wide drug concentration range of up to 650ng ml−1, bromopride was only 40 per cent bound to plasma proteins. The systemic availability of orally and intramuscularly administered solution doses of 20 mg of bromopride was 54 per cent and 78 per cent, respectively. Formulation of bromopride as the solid material in capsules delayed absorption but did not affect the extent of drug bioavailability. The pharmacokinetics of bromopride appeared similar to that of metoclopramide. No evidence for non‐linear kinetics was found when bromopride was administered orally in the dose range 10–30 mg: after single oral doses of 10, 20, and 30 mg, peak mean plasma drug concentrations were 20 ng ml−1 ± 32 per cent CV, 38 ng ml−1 ± 16 per cent CV, and 64 ng ml−1 ± 23 per cent CV, respectively.
Pharmacokinetics of orally administered hexobarbital in plasma and saliva of healthy subjects
Authors: Van Der Graaff M. , Vermeulen N. P. E. , Heij P. , Boeijinga J. K. , Breimer D. D. 
Published: October 2006

AbstractHexobarbital (HB) concentrations were determined in plasma and saliva of 8 healthy subjects, following oral administration of 500 mg HB‐Na. Mean plasma half‐lives were 3.2 ± 0.1 h, and salivary half‐lives 3.3 ± 0.2 h. Mean plasma clearance was 22.9 ± 2.3 1h−1. There was a linear relationship between HB concentrations in saliva and plasma (r = 0.92). Mean salivary levels were 34 per cent of plasma levels. Salivary pH was constant throughout the experiment, 7.06 ± 0.09. There was an inconsistent tendency of the saliva over plasma ratios to increase as a function of time. The percentage of protein binding calculated from saliva over plasma ratios was in reasonable agreement with in vitro data of equilibrium dialysis, 64.1 ± 2.6 per cent and 65.9 ± 0.8 per cent, repectively. The experiment was repeated in 4 subjects, and considerable intraindividual differences were shown to exist in saliva over plasma ratio, half‐lives, and protein binding.It was concluded that HB elimination half‐lives can relatively accurately be determined from salivary concentrations. Oral plasma clearance can only be estimated if the individual saliva over plasma ratios are known; this would require the taking of at least one blood sample during the experiment. When employing HB as a model substrate for drug metabolizing enzyme activity in vivo, the determination of its pharmacokinetic parameters, particularly oral plasma clearance as a reflection of cytochrome P‐450 activity, cannot be achieved by taking saliva samples only.
Rotary pursuit, a measure of human performance, and plasma concentrations of promethazine
Authors: Kotzan J. A. , Honigberg I. L. , Francisco G. E. , Zaman R. , Stewart J. T. , Brown W. J. 
Published: October 2006

AbstractPromethazine in doses of 50 mg has demonstrated detrimental effects upon the performance of visual tasks. The purpose of the study was to examine the relationship between the blood concentration levels of promethazine and two human performance tasks. Fifteen paid healthy male volunteers completed a randomized five‐way crossover design which included a 25 mg and 50 mg dose of the innovator dosage form, a 50 mg dose of a generic dosage form, a 50 mg solution dosage form, and a placebo. Serial blood samples were obtained in addition to performance measures of rotary pursuit and a simple force choice reaction time. Analysis of the forced choice reaction depicted a mild relationship with the blood concentration levels of promethazine. However, the measures of rotary pursuit, a more sensitive determinant of human motor performance, proved to be more related to both the promethazine blood concentration and the inherent learning which was confounded in the experiment. The degree of impaired pursuit performance and reaction time differences could be defined in terms of a linear relationship to the promethazine concentration.
The effect of food and time of administration on the absorption of diethylamine chromocarbe
Authors: Aiache J.‐M. , Faurie M. , Sibaud Y. , Kaftelip J.‐P. , Aiache S. 
Published: October 2006

AbstractIn order to evaluate the influence of food and time of administration on the absorption of diethylamine chromocarbe, a bioavailability study was performed in 8 volunteers by using a new method of plasmatic drug evaluation.The results obtained indicate that lunch has little effect on diethylamine chromocarbe absorption in comparison with the administration 0.5 h before breakfast. The bioavailability parameters Cmax, tmax, and AUC are not statistically different and the two methods of administration can be considered as bioequivalent.The absorption of diethylamine chromocarbe seems to be reduced when the drug is administered before dinner. This delay on absorption may be due to circadian rhythm of tractus gastrointestinal absorption or to the reduction of physiological activity of volunteers.