bluuebunny/crossref_metadata_2025_split huggingface dataset:
Inhibition of tumor cell growth in vitro and in vivo by 2‐methyl 9‐hydroxyellipticinium entrapped within phospholipid vesicles
Authors: Sautereau A. M. , Cros S. , Tocanne J. F. 
Published: October 2006

AbstractEncapsulation in liposomes of the antitumoral drug 2‐methyl 9‐hydroxyellipticinium and the consequences of its cytoxicity in vitro on L1210 leukemia cells and on its antitumoral activity in vivo on leukemic mice inoculated with L1210 cells are described. Provided the drugs is dissolved in the buffer below its critical micelle concentration (10−4M), it can be encapsulated in lipid vesicles with a very good yield in the form of a very stable combination with the lipids. The in vitro experiments show that 2‐CH3 9‐OH‐ellipticinium is less cytotoxic against L1210 cells when entrapped than when free in solution. The in vivo experiments on tumor‐bearing mice show that encapsulation of the drug reduces its toxicity. Encapsulation maintains the antitumoral activity of the drug or increases it if the leukemia is delayed (104 cells injected per mouse instead of 105 cells per mouse).
Modeling the pharmacokinetics and pharmacodynamics of trimazosin
Authors: Kelman A. W. , Meredith P. A. , Elliott H. L. , Reid J. L. 
Published: October 2006

AbstractThe pharmacokinetics and pharmacodynamics of trimazosin are described following both intravenous and oral administration to 6 normotensive, male volunteers. The IV and oral drug and metabolite (1‐hydroxytrimazosin) concentration data are fitted simultaneously to the same pharmacokinetic model. The pharmacodynamic response, change in systolic blood pressure following 5 min in the erect posture, is described using several possible models. The most efficient is one which attributes the response to both the parent drug and its principal metabolite. The response following oral administration is also consistent with this model.It appears that the reduction in blood pressure following administration of trimazosin at steady state may be governed by the concentration of metabolite.
The effect of activated charcoal on mouse sleep times induced by intravenously administered hypnotics
Authors: Adler Lauri J. , Waters Donald H. , Gwilt Peter R. 
Published: October 2006

AbstractThe effect of orally administered activated charcoal (AC) on the sleep times of mice following intravenous injection of various hypnotics was investigated. Preliminary studies with phenobarbital (Pb) showed that a linear relationship exists between the Pb‐induced sleep time and the logarithm of the Pb dose in both control and AC treated mice. Half‐lives of Pb in the two groups were estimated to be 8·1 and 0·9h. respectively. A linear decline in Pb‐induced sleep time with increasing dose of AC was observed up to a maximum effective dose of AC beyond which dose increments caused no further reduction in sleep time. A similar relationship was observed between sleep time and the concentration of sodium sulfate in which the AC was suspended.AC treatment resulted in an 82–88 per cent reduction in sleep time induced by administration of phenobarbital, methyprylon. glutethimide, ethchlorvynol, and methaqualone, AC had no significant effect on sleep time following amobarbital or pentobarbital administration.
The influence of sucralfate on ibuprofen absorption in healthy adult males
Authors: Anaya Arturo Lopez , Mayersohn Michael , Conrad Kenneth A. , Dimmitt Dan C. 
Published: October 2006

AbstractSucralfate (Carafate®) is a new anti‐ulcer agent the effects of which are mediated locally in the gastrointestinal tract. The use of this compound in conjunction with ulcerogenic drugs such as ibuprofen may represent a means of reducing gastrointestinal irritation. Combined oral therapy, however, requires evaluation of a potential interaction in absorption between those agents. The purpose of this study was to examine the influence of sucralfate coingestion on ibuprofen absorption. Twelve normal, healthy male subjects ingested a single oral 400 mg dose of ibuprofen alone or with sucralfate given as 1 g doses four times a day for 2 days prior to and during the study. Ibuprofen serum concentrations were measured for 12 hours following dosing. Parameters associated with rate of absorption (i.e. Cmax, tmax, Ka) were significantly altered in the presence of sucralfate (p < 0.05). In contrast, the relative bioavailability of ibuprofen was not significantly different between treatments (p > 0.05). Therefore, sucralfate does not alter the extent of ibuprofen absorption and would not be expected to change the response to that anti‐inflammatory agent.
The relationship between drug input and mean residence time in the body
Authors: Bialer Meir , Look Zee M. , Silber B. Michael , Yacobi Avraham 
Published: October 2006

AbstractThe relationship between the mean residence time after oral dosing or any other non‐instantaneous mode of administration (MRTni) was explored by a series of computer simultations. MRTni was calculated from the ratio of AUMC to AUC (where AUC and AUMC are the zeroth and first statistical moments, respectively, of the drug concentration‐time curve). A continuous linear relationship between MRTni and 1/ka or 1/kO was observed. In the ‘flip‐flop’ case where ka < K (where K is the elimination rate constant), the extrapolation from t* to infinity (where t* is the last observed plasma concentration) should be done using ka instead of K. If K is used, underestimated values of MRTni will be obtained. The findings from this investigation have practical application in the design and pharmacokinetic evaluation of novel sustained‐release dosage forms.
The effect of administration of phenytoin on the pharmacokinetics of isoxicam
Authors: Caillé G. , du Souich P. , Larivière L. , Vézina M. , Lacasse Y. 
Published: October 2006

AbstractThis study was designed to determine whether the disposition of isoxicam is influenced by the coadministration of another acidic drug, highly bound to plasma proteins and extensively metabolized, i.e., phenytoin. Ten healthy volunteers received an oral dose of 200 mg of isoxicam prior to and following the oral administration of phenytoin (100 mg) twice a day for 10 days. Eleven blood samples were drawn during the period following each dose of isoxicam. The area under the isoxicam plasma concentration‐time curve (AUC∞) increased from 389 ± 66 to 464 ± 62 μg h ml−1 (± SEM) (p < 0.05) after treatment with phenytoin. This increase was due to an increase in isoxicam bioavailability; the absorption rate constant for isoxicam increased correspondingly from 0.34 ± 0.06 to 1.16 ± 0.38 h−1 (p < 0.05). Distribution and clearance of isoxicam were probably not affected as its half‐life was not changed, its plasma peak concentration increased, and the time to reach this peak decreased. It is concluded that phenytoin increases the rate and extent of absorption of isoxicam.
Single intravenous dose and steady‐state oral dose pharmacokinetics of nicardipine in healthy subjects
Authors: Wagner John G. , Ling Teck L. , Mroszczak Edward J. , Freedman Donna , Wu Ann , Huang Bee , Massey Ian J. , Roe Robert R. 
Published: October 2006

AbstractNicardipine HCl oral doses (10–40 mg) were administered sequentially to six healthy subjects. For each regimen the capsule dose was administered every 8 hours (q 8 h) for 3 days and the plasma profiles of nicardipine and its pyridine analogue (M5) were determined following the last dose on day 4. Steady‐state plasma concentrations of nicardipine for each subject were fitted very well by the Michaelis–Menten equation. An intravenous tracer dose (0.885 mg nicardipine HCl) was administered simultaneously with the final oral dose on the fourth day of the 30 mg q 8 h regimen. The steady‐state bioavailability of nicardipine was shown to be dose‐dependent and averaged 19 per cent (10 mg), 22 per cent (20 mg), 28 per cent (30 mg), and 38 per cent (40 mg). Nicardipine undergoes linear first‐pass metabolism to M5. Other metabolic pathways are responsible for the saturable first‐pass metabolism observed for nicardipine.
Comparative quinidine plasma profiles at steady state of two controlled‐release products and quinidine sulfate in solution
Authors: Wright George J. , Melikian Armen P. , Pitts Jefferson E. , Crowe James T. , Morley Emily M. 
Published: October 2006

AbstractA study was conducted to compare, at steady state, the plasma quinidine level profiles of two commercial controlled‐release products (quinidine sulfate controlled release and quinidine gluconate controlled release) with quinidine sulfate given in solution. Twenty‐four healthy volunteers entered the study and 23 completed it. Quinidine formulations were given at 600mg day−1 for 4 days in each of three periods in a randomized crossover study. In addition to frequent blood sampling on the fourth day of each period, samples were taken during the approach to steady state to confirm by minimum plasma concentrations (Cmin) that steady state had been attained. Quinidine concentrations were measured by using a high‐performance liquid chromatographic assay specific for quinidine. The bioavailability of the two controlled‐release products relative to quinidine sulfate in solution was adequate when dose correction to account for differences in quinidine base content was done. Without dose correction, the area under the plasma concentration–time curve (AUC) for the quinidine gluconate form was 85 per cent that of the solution: an amount equivalent to the relative actual amount of quinidine base in the quinidine gluconate dosage form. The maximum plasma concentration (Cmax), Cmin, peak‐to‐trough differences, and AUC from the quinidine sulfate extended‐release form given 300mg q12h were similar to the solution given 150mg q6h. With dose correction, the quinidine gluconate controlled‐release form given q12h had equivalent AUC but larger peak‐to‐trough differences than either the quinidine sulfate extended‐release product given q12h or quinidine sulfate in solution given q6h.
Pharmacokinetics of dexamethasone and its phosphate ester
Authors: Rohdewald Peter , Möllmann Helmut , Barth Jürgen , Rehder Jörg , Derendorf Hartmut 
Published: October 2006

AbstractDexamethasone in form of its phosphate was given intravenously in two different doses (1.5mg kg−1 and 15 mg). Plasma levels of the ester and dexamethasone were measured and pharmacokinetic parameters were calculated. The results indicate no dose‐dependency of the pharmacokinetic parameters in the investigated range for dexamethasone. Conversion from the prodrug to the active form was rapid; maximum dexamethasone plasma concentrations were reached after 10 min. The results were verified by dexamethasone level monitoring in patients after chronic dosing. Predicted and achieved steady state levels agreed well.
The nonlinear pharmacokinetics of prednisone and prednisolone. II. Plasma protein binding of prednisone and prednisolone in rabbit and human plasma
Authors: Ferry Jame S. J. , Wagner John G. 
Published: October 2006

AbstractThe protein binding characteristics of prednisone and prednisolone were determined in human and rabbit plasma and in a 4.7 per cent human serum albumin (HSA) solution. The influence of prednisolone on prednisone binding in human plasma was also examined. Prednisolone exhibited nonlinear binding and prednisone linear binding characteristics in both human and rabbit plasma. Prednisone binding was not influenced by the presence of prednisolone. Prednisone binding to HSA was linear but to a degree substantially lower than observed in human plasma, suggesting the possibility that prednisone binds to other proteins in human plasma. The results support the hypothesis that the protein binding characteristics of prednisone and prednisolone do not explain the reported nonlinear pharmacokinetics of prednisone.
Pharmacokinetics of flurbiprofen in man. I. Area/dose relationships
Authors: Szpunar G. J. , Albert K. S. , Bole G. G. , Dreyfus J. N. , Lockwood G. F. , Wagner J. G. 
Published: October 2006

AbstractFlurbiprofen pharmacokinetics were studied in 15 normal male subjects after four oral doses. Plasma levels of total (bound + free) drug were monitored for 48 h and urine was collected for 96 h after the doses. All subjects demonstrated linear relationships between administered dose and total flurbiprofen AUC, indicating that oral clearance is independent of dose for the dose range evaluated in this study. Urinary recovery data indicated that the efficacy of absorption was dose independent.
High‐performance liquid chromatographic analysis, plasma protein binding and red blood cell partitioning of phenprobamate
Authors: Sun Jim X. S. , Embil Koral , Chow Diana S. L. , Lee Charles C. S. 
Published: October 2006

AbstractA new high‐performance liquid chromatographic procedure for the analysis of phenprobamate, a skeletal muscle relaxant in biologic fluids was developed. The method used a C18 reverse phase column, a mobile phase of methanol/acetonitrile/ water (33:15:52), and UV detection at 215nm. The assay procedure was applied to the determination of phenprobamate binding to rat and human plasma proteins using the equilibrium dialysis method. In addition, the red blood cell/plasma partitioning was determined in the whole blood of rats and humans. Phenprobamate exhibited a moderate binding to plasma proteins of rat (74.3 ± 2.2 per cent) and human (80.5 ± 1.1 per cent). The protein binding was concentration‐independent in the range of 10 to 80μgml−1. Phenprobamate binding to plasma proteins was also determined in the presence of 10μml−1 acetaminophen. The protein binding of phenprobamate was not significantly altered by acetaminophen (74.4 ± 0.6 per cent for rat plasma; 75.7 ± 1.6 per cent for human plasma). The distribution ratios of phenprobamate between the red blood cells and plasma were greater than unity, 1.86 and 1.59 in rat and human, respectively, indicating a preferential partitioning of the drug in the red blood cells.
Pharmacokinetic analysis of sustained‐release dosage forms of theophylline in humans: Comparison of single and multiple dose studies
Authors: Hussein Ziad , Bialer Meir , Friedman Michael , Raz Itamar 
Published: October 2006

AbstractA pharmacokinetic analysis of two sustained‐release dosage forms of theophylline (Theo‐Dur® and Theotrim®) was carried out following single and multiple dose administrations of the two formulations in five healthy subjects. Despite the prolonged absorption after administration of the two sustained‐release formulations, theoretical predictions of theophylline steady‐state levels following multiple dosages based upon data obtained from the single dose study, correlated with the data of the multiple dose study. This study shows that the recommended dose and dosage regimen of new sustained‐release formulations of theophylline can be based upon single dose studies. In the population studied, repetitive doses of 450mg b.i.d. of Theo‐Dur® and Theotrim® maintain steady‐state concentrations of theophylline within the drug's therapeutic window.
Amiodarone pharmacokinetics. II. Disposition kinetics following subchronic administration in rat
Authors: Weir Scott J. , Ueda Clarence T. 
Published: October 2006

AbstractA 30 mg kg−1 intravenous bolus of 14C‐amiodarone (19μCi kg−1) was given to male Sprague‐Dawley rats pretreated with 0 (vehicle), 25 or 100mg kg−1 day−1 of amiodarone HCl orally for 37‐42 days to determine the effects of dose and duration of administration on the disposition kinetics of amiodarone. Serial blood samples and total urine were collected over 48 hours and assayed for 14C‐amiodarone by liquid scintillation counting following separation by HPLC. In all three groups, the blood 14C‐amiodarone concentration‐time curves declined bioexponentially with terminal half‐lives (t1/2β) ranging from 14‐22 hours. No differences in β, t1/2β, or central compartment volume (Vc) were observed between the three groups of rats. In the rats pretreated with 100 mg kg−1 day−1 of amiodarone HCl for 5‐6 weeks, amiodarone clearance (CL) and steady state volume of distribution (Vss) were reduceed 52 per cent (12.2 to 5.9ml min−1 kg−1) and 41 per cent (11.73 to 6.97 lkg−1), respectively. At the lower amiodarone daily dose, no changes in CL or Vss were observed. Negligible levels of radioactivity were detected in the urine. Amiodarone accounted for approximately 30–40 per cent of the total radioactivity in each blood specimen. This study demonstrated that CL and Vss were dose‐dependent, and that β, t½β and Vc were dose‐independent. The results further suggested that the disposition kinetics of amiodarone were independent of the duration of drug administration.
Comparative steady state bioavailability of conventional and controlled‐release formulations of albuterol
Authors: Powell Mark L. , Weisberger Miryam , Dowdy Yvonne , Gural Richard , Symchowicz Samson , Patrick James E. 
Published: October 2006

AbstractA new controlled‐release (CR) dosage formulation of albuterol has been developed which is suitable for twice‐a‐day dosing. The present study was conducted in twelve healthy adult male volunteers to compare the steady state plasma levels obtained following repeated administration of a 4mg CR tablet (q12h) compared to a 2mg conventional table (q6h) for 5 consecutive days. The mean steady state plasma level‐time curves for both the CR and conventional tablet treatments were comparable over time and reproducible. There were no significant differences in the AUC or Cmax values between the two treatments. The mean 48‐h AUC values were 240.7 and 231.3h × ng ml−1 for the conventional and CR tablets, respectively, while the corresponding Cmax values ranged from 5.3 to 6.8 ng ml−1 and 5.4 to 6.5 ng ml−1. There were no significant differences in Cmin values except for one 12‐h (day 4) value. Cmin values ranged from 3.8 to 4.3 ng ml−1 and 3.0 to 4.8 ng ml−1 for the conventional and CR tablets, respectively. The data show that the 4mg albuterol CR tablet (q12h) is bioequivalent to a 2 mg conventional albuterol tablet (q6h). The CR tablet formulation will offer the advantage of increased patient compliance; additionally, the CR formulation may prove to be especially beneficial in the treatment of nocturnal asthma.
Prediction of steady‐state bioequivalence relationships using single dose data I‐linear kinetics
Authors: Jackson André J. 
Published: October 2006

AbstractSimulated data using a linear one‐ and two‐compartment body model with different absorption characteristics were used to evaluate the ability of single dose bioavailability data to predict the relationships that exist at steady state. This was done by comparing the confidence intervals obtained from single and multiple dose data sets for the parameters of Tmax, Cmax, and area under the curve from time zero to infinity (AUC0‐∞). As a consequence of Tmax and Cmax decreasing and increasing from single to multiple dosing regimens, the confidence intervals for these parameters reflected these changes. The 90 per cent confidence interval expressed as a percentage of the reference mean increased or decreased for Tmax dependent upon the ratio of Ka test/Ka reference, and decreased for Cmax while the interval for AUC0‐∞ exhibited no predictable pattern and appeared to be influenced by the amount of error in the data set. Alteration of either the dosing interval or the fraction absorbed did not affect the pattern of change in the confidence intervals for Tmax and Cmax, but the latter did result in a decrease in the interval for AUC0‐∞. Analysis of the confidence intervals for Tmax, Cmax and AUC0‐∞ in bioequivalency studies for quinidine gluconate and procainamide hydrochloride following administration of single and multiple doses to different subjects appeared to be consistent with the patterns observed for the simulated data sets.
Bioavailability of propranolol hydrochloride tablet formulations: Application of multiple dose crossover studies
Authors: Eldon Michael A. , Kinkel Arlyn W. , Daniel Jane E. , Latts Jeffrey R. 
Published: October 2006

AbstractTwo multiple dose crossover pharmacokinetic studies were carried out to determine the steady‐state bioavailability of newly formulated generic propranolol HCl tablets relative to Inderal® tablets. In Study I, 24 healthy volunteers were dosed with 4 × 10mg test tablets, 1 × 40 mg test tablet, 4 × 10 mg Inderal tablets, and 40 mg of propranolol HCl in solution. In Study II, 24 healthy volunteers were dosed with 1 × 80 mg test tablet, 1 × 80 mg Inderal tablet, and 80 mg of propranolol HCl in solution. Both studies were of randomized design with each formulation administered every 8h for 15 doses. Serial plasma samples were obtained for 8 h after morning doses on Days 4 and 5 of each treatment period and assayed for propranolol using a validated HPLC method. Mean plasma concentration‐time data for test tablets and reference tablets were superimposable in both studies.Pharmacokinetic parameters from Days 4 and 5 were combined for statistical analysis since subjects were determined to have reached steady‐state. Mean AUC, Cmax, tmax, and Cmin values were not statistically different between test tablets and Inderal tablets in either study. Based on these findings, the test tablets demonstrated the same rate and extent of propranolol absorption as did corresponding Inderal® tablets. Therefore, the test tablets and Inderal® tablets were determined to be bioequivalent.
Effects of equimolar doses of cimetidine and ranitidine on theophylline elimination
Authors: Adebayo G. I. 
Published: October 2006

AbstractThe disposition of theophylline was studied on four occasions in eight healthy adult males. The control mean theophylline half‐life and clearance were 7·32 h and 0·86 ml min−1kg−1, respectively. After 5 days pretreatment with placebo the corresponding values of 7·01 and 0·88 were not significantly different, as were those of 7·43 and 0·85 after 5 days pretreatment with ranitidine (1·2g daily). Five days pretreatment with cimetidine (1·0g daily) resulted in a significant 44·4 per cent rise in the mean theophylline half‐life and a 36·1 per cent fall in clearance. The fall in clearance correlated positively (r=0·9407) with the initial value. The volume of distribution did not change significantly throughout the study period. The fact that, at as large a dose as 1·2g daily, ranitidine did not impair theophylline metabolism suggests that similar results reported earlier with therapeutic doses of 300 mg daily cannot be ascribed to the lower dose of ranitidine employed. It is also suggested that the risk of theophylline toxicity consequent on cimetidine coadministration will be more likely in individuals with initial high theophylline clearance.
Pharmacokinetics of theophylline before and after nephrectomy in dogs
Authors: Brashear Richard E. , Veng‐Pedersen Peter , Karol Michael D. 
Published: October 2006

AbstractThe role of the kidneys in the elimination of theophylline was directly assessed using nephrectomized dogs. Data was analyzed by two different pharmacokinetic approaches. Analysis indicated that a given dosage regimen produced significantly different serum concentrations before and after nephrectomy. Model independent pharmacokinetic analysis failed to show a significant difference in parameters. A model dependent approach, using a nonlinear regression analysis employing a linear two‐compartment model, demonstrated that the differences observed could be accounted for by a change in the first order elimination kinetics.
Multiple‐dose pharmacokinetics of the new H1‐receptor antagonist tazifylline in healthy volunteers
Authors: Bruno R. , Jullien I. , Auger J. , Iliadis A. , Dow R. , McEwen J. , Cano J. P. , Pinhas H. 
Published: October 2006

AbstractThe multiple‐dose pharmacokinetics of the new H1‐receptor antagonist, tazifylline, were investigated in healthy volunteers. From single‐dose data, tazifylline appeared to be rapidly absorbed (median tmax of 0·6 h) and eliminated (t1/2 □ 1·0±0·2 h). However, plasma levels measured on days 3 and 8 of the multiple‐dose regimen (10 mg b.i.d. for 8 days) indicated moderate accumulation. A two‐compartment model best described multiple‐dose data with a terminal half‐life of 15·6 ± 7·6 h consistent with twice‐daily dosing of tazifylline.