bluuebunny/crossref_metadata_2025_split huggingface dataset:
Plasma concentrations and pharmacokinetics of dihydralazine after single oral doses to human subjects
Authors: Waller A. R. , Chasseaud L. F. , Taylor T. , Darragh A. , O'Kelly D. A. 
Published: October 2006

AbstractAfter single oral doses of 20 mg of a suspension of dihydralazine sulphate to human subjects, the peak of mean plasma concentrations of dihydralazine of 47·0 ng ml−1 ± 11·0 standard deviation (S.D.) (n = 7) was reached at 1 h. Mean concentrations declined biphasically with apparent half‐lives of 0·57 and 4·96 h respectively.Dihydralazine was partly converted to hydralazine. The peak of mean plasma concentrations of the latter drug of 3·9 ng ml−1 ± 1·7 S.D. (n = 7) occurred at 1–2 h after dosing with dihydralazine sulphate and declined to 1–5 ng ml−1 ± 1·5 S.D. at 6 h.Of the seven subjects studied, three were classified as fast and four as slow acetylators. Mean clearances appeared to be slightly more rapid in fast acetylators (1·63 1 min−1 ± 0·32 S.D.) when compared to slow acetylators (1·31 1 min−1 ± 0·31 S.D.) but this difference and differences in plasma concentrations and in areas under the plasma drug concentration‐time curves were not significant (p > 0·1).
Biliary excretion of chlorthalidone in humans
Authors: Fleuren H. L. J. , Verwey‐Van Wissen C. P. W. , Thien Th. A. 
Published: October 2006

AbstractA single oral dose of the diuretic chlorthalidone (100 or 200 mg) was given to six cholecystectomized patients with T‐tube drainage of the common bile duct, and the 24 h bile and urine were collected during 3–7 days. Urinary recovery of chlorthalidone was 23–27 per cent of the dose, which is in the range of that in healthy volunteers. Chlorthalidone concentration in bile was 11–44 times lower than urine concentration in corresponding periods, and biliary recovery was only 0·6–1·4 per cent of the dose. When compared from equal periods of sampling of bile and urine, the same relative amount of drug was found in bile, whether the 100 or 200 mg dose had been given (viz., a fraction of 2·5–4·7 per cent and 2·5–5·7 per cent of corresponding urinary amounts respectively). It was concluded that excretion into bile constitutes only a minor route of elimination for unchanged chlorthalidone. Bile samples treated with glucuronidase and sulphatase showed no increase of chlorthalidone concentration. The open acid analogue of chlorthalidone, 3‐(4‐chloro‐3‐sulphamoylbenzoyl)‐benzoic acid, was apparently not formed as a human metabolite, as evidenced by gas chromatographic analysis of both urine and bile.
A determinant solution for infinity values of multi‐exponential equations using equal time intervals
Authors: Newburger Jerold , Stavchansky Salomon 
Published: October 2006

AbstractA determinant solution for the infinity values of multi‐exponential equations using the Guggenheim method of equal time intervals is demonstrated. The resultant solution is independent of the rate constants and can be applied using data in the early non‐log‐linear phase of the process. The minimum number of data points needed for an nth exponential equation is (2N+ 1).
Pharmacokinetics of acetylmethadols I: Gas‐liquid chromatographic determination of L‐α‐acetylmethadol and its major metabolites in plasma
Authors: Tse Francis L. S. , Welling Peter G. 
Published: October 2006

AbstractA gas chromatographic method is reported for simultaneously determining acetyl‐methadol, noracetylmethadol, and dinoracetylmethadol in plasma. Minimum detectable concentrations are 10 ng ml−1 for acetylmethadol using a flame ionization detector, and 5 and 25 ng ml−l for noracetylmethadol and dinoracetylmethadol respectively using electron capture detection. Extraction efficiency is quantitative for acetylmethadol but lower for the metabolites. The method is useful for monitoring drug levels following therapeutic doses of acetylmethadol.
Pharmacokinetics of acetylmethadols II: Plasma levels of D‐ and L‐α‐acetylmethadol and their major metabolites in the dog
Authors: Tse Francis L. S. , Welling Peter G. 
Published: October 2006

AbstractThe pharmacokinetics of the synthetic narcotic agent LAAM, its pharmacologically active, demethylated metabolites NORLAAM and DINORLAAM, and also the dextro‐enantiomer DAAM, were examined following intravenous doses of all four compounds, and oral doses of LAAM and DAAM to dogs.Extensive tissue uptake of all compounds occurred following intravenous doses. NORLAAM penetrated into tissues to a greater extent than LAAM or DINORLAAM and also exhibited the longest biological half‐life (11·7 h) in plasma compared to LAAM (6·5 h) and DINORLAAM (3·6 h). The elimination rate of DINORLAAM was prolonged following oral doses of LAAM and intravenous doses of NORLAAM, and it is suggested that prolonged pharmacologic activity of LAAM may be associated with rate‐limiting demethylation of NORLAAM. DAAM was taken up exrensively by tissues but to a smaller extent than LAAM.Following oral doses, the bioavailability of LAAM as unchanged drug was 22·6 and 32·5 per cent in two dogs while that of DAAM was 4·9, 9·3, and 14·6 per cent in three dogs. Poor bioavailability of unchanged drug from oral doses appears to be due partly to first‐pass metabolism and is partially compensated for by increased plasma levels of pharmacologically active metabolites.Extensive tissue uptake of LAAM and its active metabolites, and their long plasma half‐lives, may be partially responsible for the prolonged pharmacologic activity of LAAM reported in patients maintained on this drug.
Bioavailability and disposition of prednisone and prednisolone from prednisone tablets
Authors: Rose James Q. , Yurchak Anthony M. , Nsko William J. , Powell David 
Published: October 2006

AbstractThe relative bioavailability of two 50 mg prednisone tablet formulations was determined in 18 healthy male volunteers who were not pretreated with dexamethasone. Plasma and urine samples were collected over a 24‐h period and their concentrations of prednisone and prednisolone were assayed by a specific and sensitive high pressure liquid chromatography (HPLC) method. Bioavailability was assessed by comparing the areas under the plasma concentration‐time curves and by the relative amounts of prednisone and prednisolone in urine. There were no significant differences between the bioavailability of the film‐coated and standard 50 mg tablets. Eight subjects subsequently received a 40 mg equivalent intravenous dose of prednisolone as prednisolone succinate to provide plasma concentrations of prednisolone similar to concentrations found after oral doses of prednisone. The systemic bioavailability of prednisolone, the active metabolite generated from film‐coated and standard prednisone tablets, was estimated to be 0·77±0·15 and 0·80±0·11, respectively. The nonlinear distribution, the interconversion, and the simultaneous elimination of these drugs, however, complicate any assessment of their relative and absolute bioavailability.
The effect of buffering on oxyphenbutazone absorption kinetics and systemic availability
Authors: Ducal Robert , Dupuis Claire , Bertrand Michel , Gagnon Marc‐André 
Published: October 2006

AbstractA systemic availability study comparing an investigational buffered tablet formulation of oxyphenbutazone and a commercially available product, the efficacy of which has been well established by usage, is reported. The experiment was designed to dissociate formulation factors from all other sources of variation including differences between subjects, sexes, sequences of administration, experimental periods, as well as sex by sequence, sex by period, and sex by formulation interactions. Systemic availability was assessed by conventional pharmacokinetic techniques.Results show that buffering of a tablet formulation consistently increased the rate and degree of absorption. Although the relative magnitude of bioavailability indicators is slightly different according to the method of calculation, the estimates are always higher with the buffered formulation. No statistical difference was observed for plasma concentration‐time profiles between sexes. The wide range of observed concentrations over the time interval of this study confirms other reports of individual variations in handling oxyphenbutazone. The differences noted between the two formulations may be attributed to faster dissolution rate characteristics and better dispersion of oxyphenbutazone. Some aspects of the clinical relevance of this situation are discussed briefly.
Theoretical considerations in calculation of terminal phase half‐ times following oral doses, illustrated with model data
Authors: Curry Stephen H. 
Published: October 2006

AbstractConcentrations of drugs in plasma following oral doses, when plotted as a function of time, invariably display a growth and decay curve. The terminal phase of this curve is commonly used for calculation of a half‐time (sometimes designated the ‘half‐life’) of the drug concentration in plasma. However, difficulty is often experienced in assigning a suitable time point as that of commencement of the terminal phase. This paper examines theoretically and with model data the issue of whether there is a useful systematic relation between this time and other identifiable times such as that of maximum concentration. The conclusion is reached that no rule of thumb can be applied. It is stressed that computer simulation, statistical testing for linearity, and comparison with data obtained following intravenous doses are all necessary before a conclusion can be reached that a particular half‐time has been validly assessed.
Bioavailability of propranolol and bendrofluazide formulations
Authors: McAinsh James , Holmes Brian F. , Baber Nigel S. , Young Jean 
Published: October 2006

AbstractIn this comparative bioavailability study in 12 healthy volunteers the blood level profiles of both propranolol and bendrofluazide were studied following the multiple oral administration of the drugs as a fixed combination (Inderetic®) and as a free combination at doses of 80 mg propranolol twice daily and 2.5 mg bendrofluazide twice daily.There were no statistically significant differences between the two regimens in terms of individual propranolol blood levels, half‐lives and area under the curve. The half‐lives were between 5 and 8 h. Thus the bioavailability of propranolol from the fixed combination is equivalent to that from the free combination.The mean peak bendrofluazide blood levels were slightly higher following the administration of the fixed combination. This difference was statistically significant only at 1 and 2 h after the first dose. There were no statistically significant differences between these two bendrofluazide regimens in terms of half‐life and area under the curve. Thus the bioavailability of bendrofluazide from the fixed combination is equivalent to that from the free combination.It is concluded therefore that by combining bendrofluazide and propranolol in a fixed capsule formulation does not affect significantly the systemic bioavailability of either component.
Pharmacokinetics of cefoxitin administered intramuscularly to rabbits with experimentally‐induced renal impairment
Authors: Garcia M. J. , Dominguez‐Gil A. A. , Cepeda M. , Dominguez‐Gil A. 
Published: October 2006

AbstractThe pharmacokinetics of Cefoxitin were studied in rabbits with normal renal function and with varying degrees of renal impairment induced experimentally by uranyl nitrate. All animals received a single intramuscular (i.m.) dose of 40 mg kg−1 of the antibiotic. The concentrations of Cefoxitin were determined in plasma, urine, and bile by a microbiologic plate diffusion method. The antibiotic follows a two‐compartment open kinetic model. In rabbits with renal impairment there is a decrease in α, β K12, K12, Ka and an increase in Vd and the (AUC) with respect to the values obtained for rabbits with normal renal function. Linear relationships are established between log β and logK13 and the serum creatinine. Biliary excretion of Cefoxitin is increased in states of renal impairment. A linear relationship is established between the percentage of the dose excreted in bile and the serum creatinine.
Binding of tolmetin and salicylic acid to human serum albumin as a function of temperature
Authors: Behm Harriet L. , Flynn Gordon L. , Wagner John G. 
Published: October 2006

AbstractWhen drug‐protein binding data are evaluated thermodynamically standard free energy (ΔG°), standard enthalpy (ΔH°) and standard entropy (ΔS°) are usually estimated from association constants (Ka) derived from binding data obtained at only two temperatures. Estimation of ΔH° involves the assumption of its constancy in the temperature range studied and linearity of a van't Hoff plot of In Ka versus 1/T. Sometimes the assumption of such linearity is invalid for theoretical reasons and data obtained at only two temperatures contain no information concerning linearity of this plot. We present data for the binding of both tolmetin and salicylic acid to human serum albumin as a function of temperature which make doubtful the validity of using association constants of these drugs to derive thermodynamic constants other than ΔG° values.
Isosorbide 5‐mononitrate pharmacokinetics in humans
Authors: Taylor T. , Chasseaud L. F. , Major R. , Doyle E. , Darragh A. 
Published: October 2006

AbstractWhen isosorbide 5‐mononitrate was intravenously infused at a rate of 4 mg h −1 for 2.5 h to five human subjects, its concentrations in plasma increased slowly to 185 ng ml−1 ± 5 per cent C.V. at 2.5 h and a steady‐state plasma level was not reached during the infusion. When the infusion was discontinued, plasma drug concentrations declined with an elimination half‐life of 4.2 h ± 6 per cent C.V. The systemic clearance after the infusion doses was 132 ml min−1 ± 18 per cent C.V. and the volume of distribution was 48.4 1 ± 16 per cent C. V. After equal oral doses of 10 mg, the peak plasma isosorbide 5‐mononitrate concentration of 191 ng ml−1 ±16 per cent C.V. was reached at 1.1 h ± 30 per cent C.V., and plasma levels declined with a terminal half‐life of 4.9 h. The complete systemic availability of isosorbide 5‐mononitrate indicated that pre‐systemic elimination after the oral doses was negligible. A one‐compartment open model appeared adequate to describe the plasma level data after intravenous infusion and oral doses. After single oral doses of 10 mg isosorbide dinitrate, the peak plasma concentration of the 5‐mononitrate metabolite of 72 ng ml−1 ± 27 per cent C. V. occurred at l.7h.41 per cent C.V. Approximately 50 per cent (range 22–68 per cent) of the oral dose of isosorbide dinitrate circulated in plasma as the 5‐mononitrate metabolite. The pharmacokinetics of isosorbide mononitrates are markedly different to those of the parent dinitrate and these differences follow from the greater systemic availability and volume of distribution of the mononitrates.
Plasma concentrations and bioavailability of isosorbide dinitrate and pindolol from a combination formulation
Authors: Chasseaud L. F. , Doyle E. , Taylor T. , Darragh A. 
Published: October 2006

AbstractThe plasma concentrations and bioavailability of sustained‐release isosorbide denigrate and standard‐release pindolol have been compared after administration of these drugs in combination and alone.Bioavailability parameters of isosorbide dinitrate and pindolol obtained after administration of the drugs in combination were not significantly different (P>0.05) to those obtained after administration of either drug alone.Two peaks of mean concentrations of isosorbide dinitrate occurred in plasma after administration of 30 mg of this drug in combination with 7.5 mg pindolol (4.4 ng ml−1 at 1 h and 4.5ng ml−1 at 5h), or alone (5.9ngml−1 at 2h and 5.7ng ml−1 at 5h). In each case, plasma concentrations of isosorbide dinitrate were maintained during at least 8 h, whereas the drug was not detected in plasma at 2.5 h after administration of a standardrelease formulation.The peaks of mean concentrations of pindolol were 39.7ng ml−1 at l.5h after administration of 7.5 mg drug in combination with isosorbide dinitrate and 38.0 ng ml−1 at 1 h after administration of the drug alone. Concentrations of pindolol in plasma declined with a half‐life of 3 h.
An alternative method for calculating simple pharmacokinetic parameters for zero‐order absorption and first‐order elimination processes
Authors: Bialer Meir 
Published: October 2006

AbstractAn alternative way to the classical method is presented for calculating the relevant pharmacokinetic parameters for zero‐order absorption and first‐order elimination processes. Although the equations were derived using the one compartment body model, some of them are applicable to the multicomponent body model as well. The method presented is useful whether or not a steady state is reached.
Surgically affected sulfisoxazole pharmacokinetics in the morbidly obese
Authors: Garrett Edward R. , Suverkrup Richard S. , Eberst Kathleen , Yost Richard L. , Patrick O'Leary J. 
Published: October 2006

AbstractIntestinal bypass surgery in 4 morbidly obese females (110‐150 kg) had no permanent effect on the rate or amount of sulfisoxazole absorption. The loss of weight up to 44 per cent within an individual over a year's time had no significant effect on the apparent volumes of distribution or other pharmacokinetic parameters of sulfisoxazole and its N4‐ acetylsulfisoxazole metabolite. Dosing of this drug on a mgkg− 1 basis is contraindicated. Renal clearances of sulfisoxazole were reasonably constant within a study but those of the N4‐acetylsulfisoxazole decreased with time. Integrated pharmacokinetic models were applied to plasma and urine data to estimate the metabolic clearance of sulfisoxazole and the apparent volume of distribution of the N4‐acetylsulfisoxazole. Sulfisoxazole solution is absorbed readily by primarily a zero order process after a short lag period, indicative of rate‐determining gastric emptying. The classical Bratton‐Marshall assays were compared with an HPLC assay of both drug and metabolite. There was greater confidence in plasma levels of the metabolite from the HPLC method.
Biopharmaceutical characteristics of a new propranolol/ hydrochlorothiazide tablet combination
Authors: Kraml M. , Dubuc J. , Dvornik D. , Patterson‐Kreuscherv S. , Perdue H. , Lee T. Y. , Mullane J. 
Published: October 2006

AbstractExperiments have been carried out in dogs and man to determine the effect of hydrochlorothiazide (HCT) on the pharmacokinetics of propranlol and to evaluate the bioavailability of two dosage forms containing both propranolol and HCT (40/25 and 80/25 mg, respectively). In adult male beagles, 50 mg of HCT had no apparent effect on AUC, Cmax, Tmax, and T1/2 of propranolol administered concurrently. In man, INDERIDE® (40/25 mg) and INDERIDE® (80/25 mg) were shown to be similar in bioavailability to the reference formulations, i.e. the same amount of drugs administered as the separate tablets of INDERAL® plus HYDRODIURIL®.
Bretylium pharmacokinetics and bioavailabilities in man with various doses and modes of administration
Authors: Garrett Edward R. , Green J. Russell , Bialer Meir 
Published: October 2006

AbstractThe pharmacokinetics and bioavailabilities of bretylium tosylate were studied in 9 male normal volunteers by 60 min constant rate intravenous infusions of 200, 300, and 400 mg, by intramuscular injection of 300 and 400 mg, by oral administration of 100, 200, and 400 mg in solution, and by oral administration of 200 mg tablets. The latter studies were repeated in the same 5 volunteers which were also studied by all modes of administration and at several doses. Intravenous studies showed a sum of 3 exponentials to characterize plasma level‐time studies with a terminal half‐life of 535±32 (S.E.M.) min (n=12). The urinary recovery of unchanged drug was 77±4(S.E.M.)(n = 14). Half‐lives within a subject were correlated and independent of dose. Intramuscular administration showed an apparent half‐life of first‐order invasion of 79±13(S.E.M.)min (n = 6) with no apparent dose dependency and a urinary recovery of unchanged drug of 95.4±3.2 (S.E.M.) per cent with a terminal half‐life similar to the intravenous studies. Oral solutions had smaller lag times of absorption [17±4(S.E.M.)min] than tablets [56±9 (S.E.M.)min] and longer apparent half‐lives of first‐order absorption [231 ± 23(S.E.M.)min] than tablets [87±15(S.E.M.)min]. The tablets had slightly greater bioavailabilities [27±2.3 (S.E.M.) per cent] than the oral solutions [22.1±2.2 (S.E.M.) per cent] but with no apparent dose dependencies. Renal clearances were the same for all modes of administration. Means±S.E.M. were 735±32, i.v., 686±38, i.m., and 623±57ml min−1, p.o. Apparent overall volumes of distribution were 589±401, i.v. and 450±671 (S.E.M.), i.m. The i.v. studies in three dogs confirmed the three‐compartment body model and the high overall volumes of distribution, had terminal half‐lives similar to humans and had renal clearances of 84, 164, and 207ml min−1 that were in excess of glomerular filtration.
Disposition of cyclophosphamide in the rabbit and human cornea
Authors: Schoenwald Ronald D. , Houseman Jeffrey A. 
Published: October 2006

AbstractRabbit (dark irides and albino) and human corneas were excised and mounted in a Lucite® chamber in order to determine the permeability of cyclophosphamide‐14C and to identify its metabolites. The chromatographic scans obtained from the developed thin‐layer plates showed only one peak for either rabbit or human corneas which corresponded to cyclophosphamide.By measuring the permeability of cyclophosphamide across the intact cornea, stroma alone, epithelium/stroma, and stroma/endothelium, it was possible to determine the resistance to penetration for each layer. The epithelium was the rate determining barrier, whereas both the stroma and endothelium offered little resistance. The stroma behaves as an inert sieve with drug diffusing through an aqueous media of gel‐like mucopolysaccharide interspersed by a matrix of collagen fibrils.
Automated pharmacokinetic analysis: Experiences of a user
Authors: Ruifrok Peter G. 
Published: October 2006

AbstractTwo curve‐stripping and three nonlinear regression computer programs currently in use for automated pharmacokinetic analysis were tested alone and in combination on their suitability to solve a number of pharmacokinetic problems. The five programs, NONLIN, NONLINEAR, CFT3, ESTRIP, and RUGFIT (all non‐commercial and readily available from the particular authors), were compared on these features: reliability, robustness, user convenience, and availability on macro or micro computers. The results show that if reliability and robustness are considered only, a combination of the curve‐stripping program ESTRIP with the nonlinear regression program CFT3 operates better than the other combinations. This combination is even more attractive if, in addition, user convenience and availability on micro computers are taken into account.
Thiazides XIII: Dissolution testing: A bioavailability predictor for benzthiazide tablets
Authors: Shah Vinod P. , Keys Christopher A. , King David M. , Prasad Vadlamani K. , Cabana Bernard E. 
Published: October 2006

AbstractThe dissolution characteristics of benzthiazide tablets were studied under different conditions, and were found to be very poor. It is suggested that these dissolution characteristics are predictive of poor product performance in vivo observed by other authors. The combined dissolution and bioavailability data raise questions as to the clinical value of benzthiazide products.