bluuebunny/crossref_metadata_2025_split huggingface dataset:
Age‐related differences in ophthalmic drug disposition II: Drug‐protein interactions of pilocarpine and chloramphenicol
Authors: Miller Susan C. , Patton Thomas F. 
Published: October 2006

AbstractAlthough drug‐protein interactions have been shown to be important in the transport of drugs into and through the eye, age‐related differences in ocular drug‐protein binding have not been explored. This study was designed to investigate protein binding characteristics of pilocarpine and chloramphenicol in aqueous humour and plasma from rabbits of different ages. The method of equilibrium dialysis was used to quantitate drug‐protein interactions. Younger animals showed decreased binding of chloramphenicol in plasma when compared to older rabbits. On the other hand, the interactions of both drugs with aqueous humour proteins were more extensive in younger rabbits. Age‐related differences in drug‐protein binding were not directly related to the total protein contents of the respective biological fluids. These findings suggest possible age‐related differences in the relative protein fractions contained in aqueous humour and plasma, or qualitative differences in the binding capacity of the proteins involved.
The single‐point method of dosage prediction: Pharmacokinetic basis and method optimization
Authors: Love B. L. , Tsuei S. E. , Thomas J. , Nation R. L. 
Published: October 2006

AbstractBased on the principle of superposition an expression has been established relating a drug concentration at steady‐state to a concentration after a single dose. This relationship applies for drugs with linear pharmacokinetics given at equal dosage intervals and it is independent of the route of administration. The relationship provides theoretical justification for the single‐point method of dosage prediction reported in the literature. The test conditions in the method can therefore be optimized and the limits of the method defined. The expression can also be used for individualized prediction of maintenance dose after estimation of drug half‐life in the patient with no limit to half‐life values to which it can be applied.
Comparative bioavailability and pharmacokinetics of hydrochlorothiazide from oral tablet dosage forms, determined by plasma level and urinary excretion methods
Authors: Barbhaiya R. H. , Patel R. B. , Corrick‐West H. P. , Joslin R. S. , Welling P. G. 
Published: October 2006

AbstractThe bioavailability and pharmacokinetics of two hydrochlorothiazide products were compared following single 50 mg oral doses to 20 healthy male volunteers. Plasma and urine were assayed for hydrochlorothiazide by a specific and sensitive HPLC method. Plasma profiles of hydrochlorothiazide were adequately described by a triexponential function. The bioavailability of hydrochlorothiazide from the two brands did not differ significantly as judged by the values of Cmax, tmax, AUC0→x, mean residence time, variance of residence time, and urinary excretion of unchanged drug. Close similarity was observed between urinary excretion rates and concentrations of drug in plasma.
Drug and metabolite concentrations combined in predicting steady‐state concentrations from test doses
Authors: DeVane C. Lindsay , Jusko William J. 
Published: October 2006

AbstractThe first day test dose versus steady‐state relationship for predicting drug doses was evaluated for the situation where metabolites are produced. An organ clearance model incorporated into a digital computer program simulated drug and metabolite disposition. When the terminal elimination rate for metabolite was similar to that of its precursor, the drug and metabolite concentrations could be summed for use in test dose predictions as the resulting accumulation ratios were similar. However, if an active metabolite is eliminated more slowly than its precursor, future studies should consider these concentrations separately for predictive purposes. The theoretical results agreed with concentration data obtained from a study of patients who took imipramine.
Influence of inflammatory disease on the clinical pharmacokinetics of atenolol and metoprolol
Authors: Kirch Wilhelm , Spahn Hilde , Ohnhaus Edgar E. , Köhler Hans , Heinz Ute , Mutschler Ernst 
Published: October 2006

AbstractThe influence of inflammatory disease on the pharmacokinetics of atenolol and metoprolol was investigated after administering single oral 100mg doses of the drugs to six subjects. Each subject had a respiratory tract infection with an erythrocyte sedimentation rate (ESR) of over 20 mm in the first hour and a body temperature of at least 38·5°. Since the subjects subsequently received atenolol and metoprolol when they were healthy, each person acted as his own control.Inflammatory disease had no influence on the kinetics of metoprolol. In contrast, mean peak plasma levels and AUC for atenolol were significantly lower, both by about 40 per cent, during infectious disease compared to the healthy state (p<0·05), where as renal clearance of atenolol slightly increased from 110·8 ± 14·7mlmin−1 in the healthy state to 128·21·6mlmin−1, when the ESR's were elevated. The elimination half‐life of atenolol, about 10 h, was not affected by the health status of the subjects. Reduced absorption in the gastro‐intestinal tract and enhanced elimination of atenolol from plasma might account for the decreased AUC and peak plasma levels of the drug during inflammatory disease.
Absorption and disposition characteristics of nitrofurantoin in dogs
Authors: Niazi S. , Vishnupad K. S. , Veng‐Pedersen P. 
Published: October 2006

AbstractThis study reports the disposition kinetic properties of nitrofurantoin in dogs following single intravenous and oral administration of various formulations of nitrofurantoin. Also reported here is the effect of delaying gastric emptying by food and atropine on the absorption characteristics of nitrofurantoin. The drug absorption parameters calculated using a deconvolution computer program indicate that the rate and extent of enterohepatic recycling affects the elimination and absorption rate constants and thus confound the bioavailability calculations of nitrofurantoin, heretofore unrecognized in the literature.The plasma half‐life following intravenous administration was 31 min (monoexponential equation) with little effect of enterohepatic recycling noted. Following oral administration, a biexponential equation with lag‐time was used to fit the blood levels. The absorption half‐lives were higher when nitrofurantoin was administered as a solid dosage form compared to a solution. The absorption half‐lives following tablet administration ranged from 30 to 72 min and were not affected by food or atropine. The elimination half‐lives following oral administration ranged from 19 to 87 min with significantly prolonged elimination when solid dosage forms were administered compared to solution. The extent of absorption ranged from 38 to 120 per cent. A direct correlation between the absorption and elimination half‐lives was established, indicating that increased biliary recycling direct affects the apparent disposition half‐life. The three brands of nitrofurantoin tested for bioavailability showed that the use of blood levels without appropriate corrections for biliary recycling are not suitable for bioavailability testing of nitrofurantoin. The use of urinary excretion data in evaluating nitrofurantoin bioavailability is also questioned in the study.
Systemic bioavailability and pharmacokinetics of methylprednisolone in patients with rheumatoid arthritis following ‘high‐dose’ pulse administration
Authors: Narang P. K. , Wilder R. , Chatterji D. C. , Yeager R. L. , Gallelli J. F. 
Published: October 2006

AbstractThe absolute and relative bioavailability of two methylprednisolone formulations (capsules and suspension) was determined along with its pharmacokinetics in four arthritic female patients, following an unconventional high‐dose pulse of 1 g. Plasma concentrations of the drug were measured by a sensitive and specific high‐performance liquid chromatographic (HPLC) procedure. The disposition of methylprednisolone from plasma following intravenous (i.v.) infusion of its succinate ester appeared monoexponential with a mean half‐life of 2·4 h and an apparent volume of distribution (Vd) of 50 1 (0·871 /kg). The total body clearance (Cl) averaged 15·121/h. Absolute bioavailability was assessed by comparing the areas under the plasma concentration time curves (normalized to dose) following oral administration of capsule or suspension with those of intravenous administration. No significant difference (p > 0·2) was observed when systemic availability (f, expressed in per cent) following administration of drug in capsule (f = 49·35 per cent) was compared with that obtained following the administration of drug in a suspension (f = 58·26 per cent). The difference in the observed and predicted f may be due to incomplete absorption, hepatic and/or extrahepatic metabolism of methylprednisolone. Subjective evaluation showed no side effects of this high‐dose pulse therapy in any of the patients.
Biliary secretion of sulindac and metabolites in man
Authors: Dobrinska M. R. , Furst D. E. , Spiegel T. , Vincek W. C. , Tompkins R. , Duggan D. E. , Davies R. O. , Paulus H. E. 
Published: October 2006

AbstractThe biliary secretion of sulindac and metabolites after a single 400 mg oral dose of the drug was studied in 3 elective gallbladder surgical patients following placement of an occludable T‐tube in the common bile duct. Bile and systemic plasma were sampled at frequent intervals for up to 36 h postdose. The apparent biliary clearance (V̇cl,bilc) of the prodrug sulindac is about 25 times greater than that of the pharmacologically active sulfide metabolite. The total biliary flux of drug in normal man with an uninterrupted enterohepatic cycle, calculated from V̇cl,bile and historic mean plasma drug AUC values, averages 144 and 12·2 per cent of the dose as sulindac and the sulfide metabolite, respectively. Thus, enterohepatic recycling of the drug in man is principally in the form of the prodrug which not only limits exposure of the intestine to the active moiety but also sustains systemic concentrations of active drug upon reabsorption of the prodrug.
A new metabolite of butylated hydroxyanisole in man
Authors: El‐Rashidy Ragab , Niazi Sarfaraz 
Published: October 2006

AbstractButylated hydroxyanisole (I) is one of the most commonly used food antioxidants. Its use has been suggested to inhibit a variety of carcinogenic responses. The present study on the disposition kinetics of (I) in man indicates that contrary to previous reports, (I) undergoes significant O‐demethylation in the body yielding a tert‐butyl hydroquinone. It is suggested that this metabolic conversion may be responsible for some of the in vivo activities of (I) against chemical carcinogens.
The influence of vitamin C on antipyrine pharmacokinetics in elderly men
Authors: Blanchard James , Achari Ramanuj , Harrison Gail G. , Conrad Kenneth A. 
Published: October 2006

AbstractThe influence of vitamin C on the pharmacokinetics of antipyrine was investigated in eleven elderly men aged 65–74. Antipyrine (15 mg kg−1) was administered intravenously on three separate occasions over a 7‐week period: (a) before dietary vitamin C restriction, (b) after approximately 5 weeks of dietary vitamin C restriction, and (c) after 2 weeks of vitamin C supplementation (500 mg orally twice daily). The mean plasma and leucocyte vitamin C levels (±S.D.) before vitamin C restriction were 1·26 ± 0·31 mg dl−1 and 26·6 ± 6·7 μg 10−8 leucocytes, respectively. These values decreased and then increased significantly following vitamin C restriction and supplementation, respectively. The mean plasma half‐life of antipyrine was 10·2h and the mean plasma clearance was 2·561h−1 1·73 m−2 before vitamin C restriction. No significant changes in the clearance, volume of distribution, or half‐life of antipyrine occurred during the study, indicating that short‐term alterations in vitamin C intake do not affect the pharmacokinetics of antipyrine in elderly males.
Thiazides XI: Partitioning of chlorothiazide in red blood cells after oral administration
Authors: Shah Vinod P. , Walker Mark A. , Hunt John P. , Schuirmann Donald , Prasad Vadlamani K. , Cabana Bernard E. 
Published: October 2006

AbstractUptake of chlorothiazide by red blood cells after oral drug administration was investigated. Chlorothiazide was administered to normal healthy volunteers as a solution or a tablet. Frequent blood samples were collected and analysed by a specific HPLC method. The results indicate that there is a significant uptake of chlorothiazide by red blood cells, resulting in a higher blood AUC compared to plasma AUC.
Effect of using an incorrect elimination rate constant in application of the Wagner–Nelson method to theophylline data in cases of zero order absorption
Authors: Wagner John G. 
Published: October 2006

AbstractSome authors have used an elimination rate constant derived from one theophylline treatment (e.g. the elixir) to apply the Wagner–Nelson method to concentration–time data from another treatment (e.g. a sustained‐release form). Since there is considerable intrasubject variation in the elimination rate constant of theophylline such a practice usually involves use of an incorrect rate constant. By means of theoretical treatment and simulations the effects of such a practice are shown and illustrated.
Apparent dose‐dependent oral absorption of cyclosporin a in rats
Authors: Ueda Clarence T. , Lemaire Michel , Gsell Guy , Misslin Pierrette , Nussbaumer Kurt 
Published: October 2006

AbstractThe oral absorption of cyclosporin A (CyA) was studied in rats after 6, 12, 18, and 23 mg kg−1 doses were given in an olive oil solution to determine if CyA absorption from the gastrointestinal tract was dose‐dependent. Using serial blood samples obtained at various times after the respective doses, analysis of the resultant blood CyA concentration–time curves suggested that the rate of CyA absorption for all four doses was an apparent zero‐order process. Moreover, the rate of CyA absorption appeared to be dose‐dependent, increasing as the dose of CyA increased. Similarly, the extent of CyA absorption (F) also exhibited dose‐dependent characteristics in this study. F is increased from 0·13 after the 6 mg kg−1 dose to 0·22 with the 18 and 23 mg kg−1 doses (p < 0·05). In the present investigation, the observed values for the duration of drug absorption (T), terminal first‐order rate constant (β) and corresponding elimination half‐life (T1/2β) of approximately 4–5 h, 0·030 h−1 and 21–28 h, respectively, were similar for all CyA doses. Moreover, no difference in β was observed after oral or intravenous drug administration. Absorption lag times of 1–2 h were found. The results suggested that the apparent dose‐dependent absorption of CyA observed in the present study was possibly related to the effects of olive oil on gastric emptying and that CyA might be unstable in the gastric fluids and/or metabolized by the gastric mucosa.
Biliary excretion and enterohepatic circulation of two beta‐adrenergic blocking drugs, exaprolol and propranolol in rats
Authors: Tomčíková O. , Bezek Š. , Ďurišová M. , Faberová V. , Zemánek M. , Trnovec T. 
Published: October 2006

AbstractPlasma levels and excretion of two beta‐adrenoceptor blocking drugs 3H‐exaprolol and 3H‐propranolol wereobserved up to 96 h after a single i.v. administration to rats. Terminal half‐lives of 26·8 ± 9·1 h and 51·3 ± 7·5 h were found for exaprolol and propranolol, respectively. The recovery of 3H radioactivity in feces following i.v. administration of the drus (34·2 ± 0·8 per cent and 12·0 ± 1·3 per cent 3H of exaprolol and propranolol, respectively) is of biliary origin, as 30·7 ± 3.5 per cent and 13·4 ± 3.6 per cent 3H of exaprolol and propranolol, respectively, was excreted in the bile after i.v. administration. Enterohepatic circulation of the drugs was studied using the donor‐recipient rat method. After intraduodenal administration of donor bile to the recipient rat approximately 50 per cent and 40 per cent of the biliary 3H activity of exaprolol and propranolol, respectively, was re‐excreted following absorption. A formula for calculating the amount of the substance together with its metabolites excreted in the bile, urine or feces as a result of enterohepatic circulation has been proposed.
Comparison of the bioavailability of oral, rectal and intramuscular promethazine
Authors: Schwinghammer Terry L. , Juhl Randy P. , Dittert Lewis W. , Melethil Srikumaran K. , Kroboth Frank J. , Chungi Vinod S. 
Published: October 2006

AbstractThe bioavailabilities of generic and reference promethazine 50 mg rectal suppositories were compared with that of 50 mg reference oral solution (24 subjects), and all three treatments were compared with a 50 mg reference i.m. injection (six subjects). Plasma samples were assayed by an HPLC method with triflupromazine as the internal standard. Both suppositories produced lower peak plasma concentrations (Cmax) and longer times to peak concentration (Tmax) than did the oral solution. There were no significant differences in the mean area under the plasma concentration–time curves (AUC) from 0 to 24 h among the three treatments. The Cmax of the i.m. injection was significantly higher than the other three treatments, while the Tmax of the injection was significantly shorter than the reference suppository only. The mean AUC of the injection was significantly greater than the AUCs of the other three treatments. Rectal suppositories of promethazine are more slowly absorbed than oral solutions or i.m. injections; rectal suppositories and oral solutions are less bioavailable than i.m. injections. Diminished systemic bioavailability may result from extensive first‐pass hepatic metabolism that occurs after both oral and rectal dosing. There is a high degree of inter‐subject variation in the bioavailability of promethazine rectal suppositories and oral solutions.
Relationship between total body clearance of caffeine and urine flow rate in elderly men
Authors: Trang John M. , Blanchard James , Conrad Kenneth A. , Harrison Gail G. 
Published: October 2006

AbstractThe total body clearance (CL), renal clearance (CLR), and nonrenal clearance (CLNR) of caffeine from plasma were determined following the intravenous administration of caffeine (4mgkg−1) to ten healthy men (aged 66–86 years) on three separate occasions. Positive correlations were observed between CL and urine flow rate (UFR), between CLR and UFR, and between CLNR and UFR (r = 0.8947, p = 0.0002; r = 0.8832, p = 0.0003; and r = 0.8920, p = 0.0002, respectively). Previous studies have established similar relationships between CLR and UFR for caffeine and its initial dimethylxanthine metabolites; theophylline, theobromine, and paraxanthine. A relationship between CL and UFR has not been reported previously.
On pharmacokinetics in target tissues
Authors: Weiss Michael 
Published: October 2006

AbstractBased on a two‐compartment organ model the total exposure in a target tissue, the mean tissue residence time and the peak time of the tissue concentration are evaluated in terms of tissue to blood partition coefficient and permeability coefficient (membrane permeability) of the drug, as well as the organ volume and blood flow. The total exposure is dependent upon the partition coefficient whereas the mean residence time is also affected by the permeability coefficient of the target organ. The peak time of tissue concentration following bolus intravenous injection appears to be mainly determined by the mean organ transit time and the time course of blood concentration. A tissue specific therapeutic ratio is defined using the concept of total exposure and the advantages of a local route of drug administration are discussed in this respect.
Bioavailability studies with ciglitazone in beagles I. Effect of a meal on the bioavailability of three ciglitazone dosage forms
Authors: Cox S. R. , Harrington E. L. , Hill R. A. , Capponi V. J. , Shah A. C. 
Published: October 2006

AbstractThree separate Latin square crossover studies were conducted in beagles to examine the effect of a meal on the bioavailability of a ciglitazone tablet, suspension, and solution. In these studies, drug was administered to fasted animals with either 50ml water or with 180g Purina Dog Chow and 20g butter. The data indicated that the meal significantly increased the AUC by about 40 per cent for both the tablet and the suspension but had no significant effect on the solution treatment. Comparisons across studies indicated low bioavailability in fasted animals from either the tablet or suspension relative to the solution. When drug was co‐administered with a meal, however, bioavailability appeared to be independent of dosage form.
Adriamycin‐loaded albumin microspheres: Preparation, in vivo distribution and release in the rat
Authors: Willmott N. , Cummings J. , Stuart J. F. B. , Florence A. T. 
Published: October 2006

AbstractAdriamycin‐loaded bovine albumin microspheres have been prepared by a technique that allows preparation and administration to animals on the same day. Criteria adopted for injection were that microspheres should be stable and of a size such as to become trapped in capillary beds. These conditions were fulfilled by preparing microspheres using glutaraldehyde concentrations greater than 0.5 per cent and the appropriate combination of stirring speed and continuous phase viscosity. After systemic administration rats were sacrificed at intervals and major visceral organs examined for entrapped microspheres and serum for released drug. Microspheres sieved out in the first capillary bed encountered, the lung, then following biodegradation they disappeared at rate dependent on the amount of cross‐linking agent used in their preparation. In contrast to bolus injection, serum drug levels after microsphere administration indicated an initial rapid release followed by a more protracted phase lasting at least 24 h. This latter observation is consistent with drug release during biodegradation of carrier.
Pharmacokinetics of furosemide after three different single oral doses
Authors: Waller Elaine S. , Massarella Joseph W. , Tomkiw Motria Sharanevych , Smith Robert V. , Doluisio James T. 
Published: October 2006

AbstractFurosemide solution was orally administered to 21 healthy adult males to determine dose proportionality over the dose range used and the reproducibility of disposition following a repeated dose. Furosemide solution was given in doses of 20, 40, and 80mg, with the 40 mg dose repeated once. Blood was collected for 12 hours post‐dose and urine for 24 hours. The maximum plasma concentrations resulting from 20, 40, and 80mg doses were significantly different (p < 0.05). Dose normalized maximum concentrations for the 20 and 80 mg doses were significantly different (p < 0.05). Mean time to Cpmax was 50 minutes, with no differences observed among doses. Plasma AUCs were significantly different (p < 0.05) for 20, 40, and 80mg. Dose normalized AUCs were not significantly different. Mean amounts of furosemide in urine (Xu) were 9.62, 16.7, and 32.0 mg for the 20, 40, and 80 mg doses, respectively. These amounts were significantly different (p <0. 05); dose normalized amounts were not significantly different. Renal clearances of furosemide following the three doses were not significantly different. Regressions of Cpmax, AUC and Xu on dose were significant. There were no significant differences in Cpmax, tmax, AUC or Xu for 40 mg given on two separate days. Renal clearance of furosemide was statistically different for 40mg given on two separate days, but the difference was not clinically significant. The pharmacokinetics of furosemide are linear over the dosage range studied. Furosemide 40 mg given on two separate days results in similar disposition parameters.