bluuebunny/crossref_metadata_2025_split huggingface dataset:
Blood cyanide levels in mice after administration of amygdalin
Authors: Hill Helene Z. , Backer Ronald , Hill George J. 
Published: October 2006

AbstractOral doses of amygdalin and intraperitoneal (i.p.) doses of potassium cyanide (KCN) in the near‐lethal range were administered to CD2F1 female mice. Blood cyanide levels were then measured as a function of time. The maximum cyanide level after amygdalin administration was reached at about 1½ to 2 h and was within the range of values seen after KCN administration. Behaviour of mice correlated with the time of maximum blood cyanide level. Acute distress was observed at times when the cyanide level was highest. There was great variability in the nature and magnitude of the response in individual mice. The ability of the contents of various regions of the gastrointestinal tract and of tumour tissue to release cyanide from amygdalin was assessed. Stomach and upper intestine had little activity while the lower end and the faeces released large amounts. Again, there was a large variation between mice. These results are interpreted to mean that enteric contents are primarily responsible for the release of cyanide from ingested amygdalin. Freshly minced tumour tissue released negligible amounts of cyanide. Ten‐fold higher doses of amygdalin administered i.p. produced very small increases in blood cyanide levels and no toxic behaviour. The doses used are comparable to doses which might be ingested by patients receiving oral amygdalin or Laetrile and indicate that oral amygdalin is potentially extremely dangerous.
Bioavailability of atenolol formulations
Authors: McAinsh James , Simpson Wilfred T. , Holmes Brian F. , Young Jean , Ellis Stuart H. 
Published: October 2006

AbstractIn this comparative bioavailability study two tablet formulations of atenolol (sales and clinical trial) were compared with an oral solution. Twelve healthy adult male volunteers received, on a cross‐over basis, on three separate occasions, 100 mg oral dose of the three formulations of atenolol. Bioavailability was based on concentrations of atenolol in whole blood and urine. The atenolol blood levels peaked at approximately 3 h after dosing, with individual values ranging from 0·21 to 0·92 μg ml−1 (a four‐fold difference), with all three formulations. Three‐fold variations among subjects occurred in the areas under the curve (AUC) and urinary recoveries. The average elimination half‐life of atenolol was between 6 and 7 h for all three formulations. Some statistically significant differences were observed between the tablets and the aqueous solution: the AUC (∞) and mean peak blood concentrations were significantly greater with the U.K. sales tablet than the solution, and the mean concentrations in the blood at certain specified times after administration were significantly greater with the two tablet formulations than the solution. The profiles of absorption and excretion of the two tablet formulations were similar.No adverse reactions were encountered in this study and all subjects completed the study without incident.
Review article cisplatin: Chemistry, distribution and biotransformation
Authors: Long D. F. , Repta A. J. 
Published: October 2006

AbstractA review of the use of cisplatin in cancer chemotherapy in humans is presented. The emphasis is placed on the chemistry, in vivo distribution and biotransformation of this agent. The existing literature pertinent to the physicochemical properties of cisplatin and structure activity relationships of platinum coordination complexes is reviewed. The chemistry of this drug, both in aqueous media and in biological systems is discussed as well as current analytical methodology used for monitoring ‘cisplatin levels’ in biological fluids. Recent advances in analytical methodology specific for cisplatin are also presented and recent findings in the area of the possible biotransformations of this important anticancer agent are discussed.
Detection and metabolism of fencamfamine and the influence of acetazolamide on its urinary excretion
Authors: Delbeke F. T. , Debackere M. 
Published: October 2006

AbstractA gas‐chromatographic (g.l.c.) method with electron‐capture (e.c.) detection is described for the simultaneous quantitative determination of nanogram concentrations of 2‐ethylamino‐3‐phenyl‐norbornane (Fencamfamine, REACTIVAN®) and its metabolite 2‐amino‐3‐phenylnorbornane in urine.The renal excretion of fencamfamine and its metabolite after oral administration to humans was followed over a period of several days. The excretion of both substances was affected by urinary pH. Excretion peaks were obtained 2–4 h after ingestion and the total amount excreted during 80 h varied from 11.9 to 33.2 per cent. Based on urinary values, the biological half life of fencamfamine was 16 h.The intake of acetazolamide shortly after fencamfamine resulted in a decrease of the fencamfamine excretion and a suppression of the metabolite output during at least 10 h. Acetazolamide did not influence the percentage of the doses excreted during 80 h.No changes occurred in urinary fencamfamine or metabolite concentrations during storage of the urine at — 18° for 6 weeks.
The effect of increased caffeine intake on the metabolism and pharmacokinetics of theophylline in man
Authors: Monks T. J. , Lawrie C. A. , Caldwell J. 
Published: October 2006

AbstractThe metabolism and pharmacokinetics of intravenously administered theophylline (100 mg) have been investigated in three healthy male volunteers who consumed 6 bottles day of a cola beverage, in addition to their usual intake of methylxanthines, for 7 days prior to and during the study. Five urinary metabolites were detected in addition to unchanged theophylline, that is 3‐methylxanthine, 1.3‐dimethyluric acid, 1‐methyluric acid, and two minor unknown metabolites. The elimination of theophylline, 1.3‐dimethyluric acid, 1‐methyluric acid, and the two unknowns was described by first‐order kinetics, whereas that of 3‐methylxanthine was described by Michaelis‐Menten kinetics. The results have been compared with those previously obtained in the same volunteers while consuming their usual intake of methylxanthine‐containing foods and beverages, and this shows that the addition of extra methylxanthines to the diet does not influence the disposition of theophylline. This is in marked contrast to the effect of deprivation of dietary methylxanthines on theophylline metabolism. The results are discussed in terms of the influence of methylxanthines on theophylline metabolism, and of its possible dose‐ dependency.
Bioavailability of sustained release propranolol formulations
Authors: McAinsh James , Baber Nigel S. , Holmes Brian F. , Young Jean , Ellis Stuart H. 
Published: October 2006

AbstractIn this comparative bioavailability study two sustained release capsule formulations of propranolol, one a clinical trial formulation and the other the U.K. sales formulation (‘Inderal’ LA), were compared with a conventional ‘Inderal’ tablet. Twelve healthy adult male volunteers received, on a cross‐over basis, on three separate occasions, 160 mg oral doses of three formulations of ‘Inderal’. Bioavailability was based on concentration of propranolol in whole blood. The peak blood level and area under the propranolol blood level curve fell as the dissolution time increased. The half‐lives of the three formulations were inversely proportional to their dissolution rates, those of the sustained release formulations being considerably longer than that of the conventional tablet.The 160 mg ‘Inderal’ tablet produced a rapid 90‐fold decline over 24 h in propranolol blood levels following a high initial peak. By comparison both sustained release formulations showed a less rapid fall in systemic levels and gave higher blood levels at the end of 24 h and plateau values between 8 and 14 ng ml −1.The ‘Inderal’ LA sustained release formulation gave consistently higher propranolol blood levels than the clinical trial sustained release formulation. This result is in good agreement with their dissolution profiles. The lowering of the systemic bioavailability as the dissolution time increases is thought to be due to an increased metabolism of propranolol.
The concentrations of cephalosporins in tissue fluid of rats with localized infection
Authors: Polacek I. 
Published: October 2006

AbstractRats implanted with multiperforated subcutaneous plastic capsules were used as a model for study of the penetration of four cephalosporins into sites infected with Escherichia coli. The concentrations of the antibiotics were determined in uninfected and infected cages microbiologically up to 4 h after treatment. All four cephalosporins entered infected capsules faster than the control ones and the peak concentrations were attained 30–60 min earlier. The clearance of the antibiotics from infected capsules was faster than from uninfected ones, probably due to inactivation by microbial β‐lactamase(s). Serum protein binding may account for differences in the penetration rate of cephalosporins, but serum level and serum half‐time seem to contribute to their kinetic profile in tissue fluid.
The pharmacokinetics of acebvutolol in man, following the oral administration of acebutolol hcl as a single dose (400 mg), and during and after repeated oral dosing (400 mg, b.d.)
Authors: Gulaid A. A. , James I. M. , Kaye C. M. , Lewellen O. R. W. , Roberts E. , Sankey M. , Smith J. , Templeton R. , Thomas R. J. 
Published: October 2006

AbstractThe pharmacokinetics of acebutolol have been studied in eight healthy male volunteers following the oral administration of acebutolol hydrochloride (‘Sectral’, May & Baker) as a single dose (400 mg), and during and after repeated oral dosing (400 mg, b.d. for 56 days).Following single dose administration, considerable inter‐subject variation in plasma levels of parent drug and the major metabolite, diacetolol. was evident. Acebutolol appeared to be eliminated from plasma in a bi‐phasic manner, and this was confirmed from urinary excretion rate data. Mean initial and terminal half‐lives of about 2 and 11 h, respectively, were determined. Plasma levels of diacetolol were greater than those of parent drug from 3 to 4 h following dose administration. Total urinary excretion of diacetolol was generally greater than that of acebutolol.During repeated dosing, steady‐state plasma levels of acebutolol and diacetolol were achieved in 6 volunteers. Acebutolol did not appear to stimulate or inhibit its metabolism.
Butriptyline: Human pharmacokinetics and comparative bioavailability of conventional and sustained release formulations
Authors: Bourgouin Jean , Gagnon Marc‐Andre , Elie Robert , Dvornik Dushan , Gonzalez Ramona , Kraml Michael 
Published: October 2006

AbstractThe pharmacokinetics and relative bioavailability of butriptyline from conventional and a sustained release (SR) formulation have been studied in a panel of 14 volunteers. A single oral dose of 75 mg butriptyline hydrochloride was administered and a 2 × 2 latin square design was followed. Pharmacokinetic modelling has shown that the plasma butriptyline concentration/time profile is adequately described by a two‐compartment open model; good agreement was obtained for the model‐fitted and measured parameters. The SR formulation was shown to possess sustained release characteristics as evidenced by the increase in Tmax for 2.6 to 7.5 h, the decrease in Cmax from 46.5 to 20.3 ng ml−1, and a three‐fold increase in ‘half‐value duration’ (HVD). The changes have been achieved without any significant decrease in the relative bioavailability of the SR formulation. The half‐life of butriptyline in plasma was about 20 h and was not formulation dependant.
Rifaprim (rifampicin plus trimethoprim): Pharmacokinetics and effects on the normal flora of man
Authors: Brumfitt W. , Hamilton‐Miller J. M. T. 
Published: October 2006

AbstractTen healthy volunteers were given ‘Rifaprim’ in the dosage recommended for the treatment of urinary infections in man (rifampicin 300 mg + trimethoprim80 mg in the morning and double these amounts at night, for 7 days). Levels of both drugs in the serum and urine were determined on the first and last days. The results show that trimethoprim was always present in the serum in amounts sufficient to suppress the emergence of resistance to rifampicin. In the urine, inhibitory concentrations of each drug were present throughout the course of treatment. Aerobic organisms were largely eliminated from the gut and reappeared after treatment still sensitive to both antibiotics: the anaerobic moiety persisted and became resistant to rifampicin. Changes in nasopharyngeal flora were relatively minor. Thus, this dosage regimen of ‘Rifaprim’ contains enough trimethoprim to prevent the emergence of resistance to rifampicin among urinary pathogens under normal circumstances (i.e. provided the organisms are initially sensitive to trimethoprim).
The assay and absorption kinetics of oral theophylline−7‐acetic acid in the human
Authors: Sved S. , McGilveray I. J. , Beaudoin N. 
Published: October 2006

AbstractA sensitive and specific method for the estimation of theophylline−7‐acetic acid in plasma by high performance liquid chromatography is described. Acidified plasma is extracted with chloroform‐n‐butanol (85: 15), back extracted with phosphate buffer (0.5 moll−1, pH 6.5), and finally the acidified aqueous phase extracted again with chloroform‐butanol. After evaporation of the extract the residue is redissolved in the chromatographic mobile phase (hexane‐dichloromethane‐ethanol‐acetic acid, 10:86: 3:1) and chromatographed on silica gel. The method was used to follow the plasma theophylline‐7‐acetic acid concentrations in two volunteers after single oral doses of 1.0 g of the drug. The results confirm previous reports, based on urine data and on plasma data following intravenous administration, that the drug is poorly absorbed (apparent bioavailability of 1 and 2 per cent), rapidly eliminated (half‐life of 1.0 and 2.4 h) and not converted to theophylline.
Age‐related differences in ophthalmic drug disposition I. Effect of size on the intraocular tissue distribution of pilocarpine in albino rabbits
Authors: Miller Susan C. , Patton Thomas F. 
Published: October 2006

AbstractIt has previously been documented that substantially different aqueous humour drug levels are observed in rabbits of different ages when the same dose of pilocarpine is instilled into the eye. Also, it has been shown that the aqueous humour volume ratio for rabbits of different ages can be used to predict aqueous humour levels of pilocarpine attained after topical dosing. In the present study, concentrations of pilocarpine in the cornea, aqueous humour, iris‐ciliary body, lens, and vitreous humour were determined in both 20‐day old and 60‐day old rabbits following the topical administration of identical doses of drug. For tissues other than the aqueous humour and iris‐ciliary body, consideration of only tissue size differences between rabbits of different ages will not suffice to explain the observed differences in pilocarpine concentration. Any attempt to develop rational age‐related dosage modifications for ophthalmic drugs must include a consideration of functional and developmental differences as well as size effects.
Pharmacokinetic evaluation of betameth asone and its water soluble phosphate ester in humans
Authors: Loo J. C. K. , McGilveray I. J. , Jordan N. , Brien R. 
Published: October 2006

AbstractTwo betamethasone tablet formulations, and a betamethasone phosphate solution were compared in a plasma level study. The tablet formulations (A and B) and a solution of betamethasone phosphate (C) were administered in single 2 mg doses to nine volunteers according to a three times repeated Latin square design. Plasma samples were obtained over 27 h following each dose and plasma was analysed for betamethasone by radioimmunoassay.Pharmacokinetic evaluation of the data, obtained according to the one‐compartment open model, indicated that there were no significant differences between the extent of absorption, and the first‐order elimination rate constants. As would be expected, the solution (C) gave a faster absorption rate than tablets A and B.
Comparative binding affinities of tamoxifen, 4‐hydroxytamoxifen, and desmethyltamoxifen for estrogen receptors isolated from human breast carcinoma: Correlation with blood levels in patients with metastatic breast cancer
Authors: Fabian Carol , Tilzer Lowell , Sternson Larry 
Published: October 2006

AbstractThe relative ability of the antiestrogen, tamoxifen, and its monohydroxy and desmethyl metabolites to displace tritiated estradiol from estrogen receptors isolated from human breast carcinoma was determined. 4‐Hydroxytamoxifen binds to the estrogen receptor with affinity equal to estradiol, and with 25–50 times higher affinity than does tamoxifen. Desmethyltamoxifen binds to the estrogen receptor with < 1 per cent of the affinity of tamoxifen. Blood level determinations of tamoxifen species in breast cancer patients receiving the drug indicated that after 3 weeks of therapy, desmethyltamoxifen levels were 1.2–1.8 times greater than tamoxifen levels and 4‐hydroxytamoxifen levels were 2–18 per cent of parent drug concentrations. Thus, because of its high affinity for the estrogen receptor, the 4‐hydroxy metabolite may play a significant antiestrogenic role following tamoxifen therapy, despite its low relative abundance. Desmethyltamoxifen, on the other hand, may have only minor importance as an anti‐estrogenic agent following tamoxifen treatment, due to its poor affinity for the estrogen receptor coupled with blood levels that are at most 75 per cent greater than tamoxifen levels at steady state.
HPLC determination of benzthiazide in biologic material
Authors: Meyer Marvin C. , Hwang Philip , Straughn Arthur B. , Rotenberg And Keith 
Published: October 2006

AbstractAn assay was developed for benzthiazide in plasma, urine and feces, using high performance liquid chromatography (HPLC). A reverse‐phase column was employed, with quantitation at 280 nm, using polythiazide as an internal standard. In three of four human subjects who received a 50 mg benzthiazide tablet the plasma concentrations were below the 10 ng ml−1 sensitivity limit of the assay, and the urinary recovery averaged less than one per cent of the dose. One subject received a 50 mg dose as both a tablet and a solution; the urinary recoveries for these two doses were 1.7 and 10.4 per cent, respectively. Fecal samples, obtained from two subjects who received 50 mg tablets, were estimated to contain approximately 80 per cent of the administered dose.
Quantitation of iprindole in plasma by GLC
Authors: Caillé G. , De Montigny C. , Besner J‐G. 
Published: October 2006

AbstractA specific, sensitive, rapid, and reproducible method for iprindole in human plasma was developed using gas chromatography with trimipramine as internal standard. The sensitivity of the method is of S ng ml−1 and a linearity was obtained for concentrations ranging from 12.5ngml−1 to 100ngml−1 with a regression coefficient of 0.9872. The plasma levels of iprindole were determined in five healthy volunteers following the administration of a single oral dose of 60 mg and in four patients admitted for endogenous depression after a 3‐week administration of 90mgd−1. Following a single oral dose to healthy volunteers, the maximum concentrations occurred between 2 and 4h after administration of the drug and the mean half‐life value was 52.5 h. In patients the steady‐state concentrations of iprindole ranged between 18 and 77ngml−1.
Antipyrine clearance, aminopyrine N‐demethylase, and bilirubin udp‐glucuronyl transferase activity in patients with amoebic liver abscess
Authors: Narang A. P. S. , Datta D. V. , Mathur V. S. 
Published: October 2006

AbstractThree indices of drug metabolism, antipyrine clearance in vivo, and aminopyrine N‐demethylase and bilirubin UDP‐glucuronyl transferase activity in liver biopsies, were studied in fifteen patients with amoebic liver abscess (with and without jaundice). The mean (± S.E.) antipyrine half‐life in patients with jaundice was 21.64 (±1.52)h and in patients without jaundice was 19.36 ( ± 0.93)h. It was significantly prolonged in both groups of patients as compared to controls (11.63 ± 0.86 h). It showed a good correlation with serum albumin (p<0.01), prothrombin time index (p<0.01), and aminopyrine N‐demethylase (p<0.05). Aminopyrine N‐demethylase was found to be decreased in patients without jaundice but no significant change could be observed in patients with jaundice. Bilrubin UDP‐glucuronyl transferase showed no significant change in either of the groups.
The effect of hydralazine on the pharmacokinetics of three different beta adrenoceptor antagonists: Metoprolol, nadolol, and acebutolol
Authors: Jack David B. , Kendall Martin J. , Dean Sandra , Laugher Steven J. , Zaman Razia , Tenneson Michael E. 
Published: October 2006

AbstractThe effect of hydralazine on the pharmacokinetics of metoprolol, nadolol, and acebutolol has been studied by measuring drug concentrations in plasma, serum, and urine. Metoprolol is affected by hydralazine, the AUC and Cmax being significantly increased. The kinetics of acebutolol and its major metabolite, diacetolol, are unaffected. Poor absorption of the polar beta blocker, nadolol, does not allow a firm conclusion to be drawn regarding the effect of hydralazine. It is concluded that only beta blockers with a substantial first‐pass loss are likely to be significantly affected by hydralazine.
Bioavailability of phenylbutazone from a new enteric‐coated formulation with superior dissolution characteristics
Authors: John V. A. , Goldsborough S. , Morrison P. J. , Rogers H. J. , Spector R. G. , Bradbrook I. D. 
Published: October 2006

AbstractThe bioavailability of an improved formulation of enteric‐coated phenylbutazone with faster dissolution, more consistent in vitro rate of drug release and improved stability was compared in 8 normal subjects at doses of 100 and 200 mg with commercially available Butacote®. Phenylbutazone was more rapidly absorbed from the new formulation and higher plasma concentrations were achieved at shorter intervals after dosing.Drug elimination rate was unaffected by reformulation and despite faster absorption the total amounts of drug reaching the circulation from the new and commercial products were similar. It was concluded that replacing Butacote® by the new formulation would provide the same therapeutic benefit.
Relative bioavailability of acetazolamide tablets
Authors: Straughn Arthur B. , Gollamudi Ramachander , Meyer Marvin C. 
Published: October 2006

AbstractPlasma acetazolamide concentrations were determined enzymatically after administration of three tablet dosage forms and a reference solution to 12 human subjects in a crossover study. Two of the tablet products represented different lots from the same manufacturer. There were no significant differences in area under the plasma level‐time curves among the four treatments. However, significant differences were found among tablets in terms of peak plasma concentration and time to reach peak concentration. These apparent differences in rate of absorption were correlated with in vitro dissolution data obtained in pH 1.5 dissolution medium.