bluuebunny/crossref_metadata_2025_split huggingface dataset:
The effect of food and antacid on the absorption of fendosal
Authors: Wills Robert J. , Velagapudi Raja B. , Puri Surendra K. , Yakatan Gerald J. 
Published: October 2006

AbstractFendosal(200 mg) was given orally to each of two separate groups of twelve healthy male volunteers on separate occasions to assess the influence of food or antacid on the bioavailability of fendosal. Blood samples (20ml) were drawn during 12 hours postdosing and fendosal plasma concentrations were quantitated by a validated fluorescence technique. Food was shown to have no significant effect (p >0.05) on fendosal bioavailability. However, the bioavailability of fendosal in the presence of an antacid was reduced by 80 per cent. In vitro studies suggested that a complexation between unionized fendosal and the metal ions contained in the antacid may be responsible for the decrease in the rate and extent of absorption observed in vivo.
Bioequivalence of a sustained‐release isosorbide dinitrate formulation at steady‐state
Authors: Taylor T. , Chasseaud L. F. , Major R. M. , Leaf F. C. , Bonn R. , Darragh A. , Lambe R. F. 
Published: October 2006

AbstractIsosorbide 2,5‐dinitrate and its pharmacologically active metabolites, isosorbide 2‐nitrate and isosorbide 5‐nitrate, in plasma accumulated to the predicted steady‐state after five consecutive oral doses of sustained‐release tablets containing 40 mg isosorbide dinitrate at 12‐h intervals and after five consecutive oral doses of reference standard‐release tablets containing 20 mg at 6‐h intervals to 12 subjects in a crossover study. The comparative bioavailability of isosorbide dinitrate, isosorbide 2‐nitrate and isosorbide 5‐nitrate from the sustained‐release tablet was 110 per cent (p > 0.05), 89 per cent (p > 0.05), and 89 per cent (p < 0.05), respectively, of that from the reference standard‐release tablet. The isosorbide dinitrate plasma level data were the more variable, as expected for a drug of low systemic availability subject to extensive first‐pass elimination. The posterior probability that the true bioavailability of isosorbide dinitrate was included within the usually accepted limits of 80–120 per cent was 0.74, a value which is probably insufficient to justify claims of bioequivalence with the reference formulation in respect of extent of availability. In contrast, the posterior probability that the bioavailability of the metabolites isosorbide 2‐ and 5‐nitrate was included within these limits was 0.90 and 0.98, respectively. On the basis of the mononitrate data, these two formulations may be judged bioequivalent in respect of extent of availability despite a formal statistically significant formulation‐related effect in the analysis of variance of the isosorbide 5‐nitrate bioavailability data. Claims of bioequivalence of isosorbide dinitrate sustained‐release formulations may be more economically justified by analysis of the mononitrate plasma concentrations, although concentrations of the formulated parent dinitrate should also be known.
Lack of effect of liver disease on the pharmacokinetics of acebutolol and diacetolol: A single dose study
Authors: Zaman R. , Jack D. B. , Wilkins M. R. , Kendall M. J. 
Published: October 2006

AbstractThe pharmacokinetics of acebutolol and its major metabolite, diacetolol, following a single 400 mg oral dose, were investigated in patients with liver disease. No significant differences were found in any of the parameters measured.
A pharmacokinetic comparison of cephalexin and cefadroxil using HPLC assay procedures
Authors: Welling Peter G. , Selen Arzu , Pearson John G. , Kwok Florence , Rogge Mark C. , Ifan Agber , Marrero Diana , Craig William A. , Johnson Curtis A. 
Published: October 2006

AbstractThe pharmacokinetics of cephalexin and cefadroxil were compared following single 500 mg oral doses to 12 healthy male volunteers. Doses were administered after an overnight fast according to a crossover design. Plasma and urinary levels of both compounds were determined by HPLC procedures. Cephalexin was absorbed rapidly, achieving a mean peak plasma level of 17.5 μg ml−1 at 1 h, compared to 16 μg ml−1 at 1.8 h for cefadroxil. Elimination half‐lives of cephalexin and cefadroxil were 0.7 and 1.1 h, respectively. The area under the cefadroxil plasma curve was significantly larger than that for cephalexin. However, after allowing for differences in elimination rate constants and assuming equal distribution volumes, plasma data indicated the compounds were equally well absorbed. Only 70 per cent of cefadroxil was recovered in urine compared to 87 per cent of cephalexin during the 12 h following drug administration. The therapeutic significance of the different pharmacokinetic characteristics of cephalexin and cefadroxil, if any, may be a function also of their pharmacologic activity and/or the sensitivity of the target organism.
Concentration‐dependent clearance of procainamide in normal subjects
Authors: Coyle James D. , Boudoulas Harisios , Mackichan Janis J. , Lima John J. 
Published: October 2006

AbstractFour normal volunteers each received two intravenous doses of PA. The mean low dose was 3.30 mg kg−1 (infused over 20 minutes) while the mean high dose was 12.5 mg kg−1 (infused over 60 minutes). Blood samples were collected for 12 hours and urine was collected for 48 hours after each dose. PA concentrations were determined by both HPLC and fluorescent immunoassay methods. The reported concentrations and pharmacokinetic parameters are from the HPLC data unless otherwise indicated. The mean peak serum PA concentrations resulting from the low and high doses were 3.18 and 9.07 μg ml−1, respectively. Total PA clearance averaged 763 ml min−1 and 577 ml min−1 while renal clearance averaged 360 ml min−1 and 318 ml min−1 after the low and high doses, respectively. Concentration‐dependent decreases in nonrenal PA clearance ranged from 31 to 43 percent (p < 0.05) in the four subjects. Total clearance decreases ranged from 4.7 to 36 per cent (p < 0.05). Differences between doses in renal clearance, elimination rate constant, and volume of distribution were not statistically significant. This study demonstrates that the nonrenal and total clearances of PA are concentration‐dependent in normal subjects at therapeutic plasma PA concentrations and suggests that the total clearance changes are of sufficient magnitude to be clinically important.
Effects of ibuprofen on the disposition kinetics of phenytoin in pregnant rats
Authors: Cleveland Patricia A. , Ueda Clarence T. 
Published: October 2006

AbstractThe effects of ibuprofen on maternal phenytoin pharmacokinetics and fetal phenytoin acquisition were investigated in 19‐day gestation Sprague—Dawley rats. A 5 mg kg−1 bolus injection of 14C‐phenytoin was given with and without (control) pretreatment with 12.5 mg kg−1 of ibuprofen. Maternal plasma and fetal whole body samples were obtained at various times after the phenytoin bolus and evaluated simultaneously using a three‐compartment maternal‐fetal model. Ibuprofen pretreatment increased the maternal plasma clearance of phenytoin about three‐fold and the overall apparent volume of distribution almost four‐fold. No changes in the volume of the maternal central compartment or terminal first‐order disposition rate constant were observed. Additionally, the maternal‐to‐fetal clearance of phenytoin was not altered in the ibuprofen‐treated rats. No differences in the apparent fetal volume of distribution or areas under the fetal phenytoin concentration‐time curves were observed between the control and ibuprofen‐treated rats. The results of this study were consistent with ibuprofen‐induced alterations in organ and tissue blood perfusion and demonstrated that, while the maternal disposition kinetics of phenytoin were altered by sodium ibuprofen coadministration, the maternal changes did not affect the extent of fetal exposure to phenytoin.
Michaelis—Menten elimination kinetics: Areas under curves, steady‐state concentrations, and clearances for compartment models with different types of input
Authors: Wagner John G. , Szpunar Gregory J. , Ferry James J. 
Published: October 2006

AbstractFor single bolus administration, intermittent bolus administrations to steady‐state, a single dose as a zero order input, intermittent zero order inputs to steady‐state, and continuous zero order input to steady‐state, and for both simple Michaelis—Menten elimination and parallel Michaelis—Menten and first order elimination, the appropriate equations are given for the areas, AUC 0–∞ or AUC 0–τ, steady‐state concentrations, and clearances. Some 20 new equations have been derived. For the case of first order input and Michaelis—Menten elimination, no solution is given but the effect of input rate on systemic availability is reported following some numerical integrations.The effect of slow input in reducing systemic bioavailability when Michaelis—Menten elimination kinetics are operative is stressed and the implications of this in the field of sustained‐release medication mentioned.
Pharmacokinetics of theophylline in protein‐calorie malnutrition
Authors: Jung Donald 
Published: October 2006

AbstractThe influence of protein‐calorie malnutrition (PCM) on the disposition of theophylline was investigated in male Sprague‐Dawley rats fed for four weeks on a 23 per cent (control) or 5 per cent (low) protein diet ad lib. Dietary protein deficiency led to a decrease in body weight gain, plasma proteins. albumin, microsomal proteins, and cytochrome P‐450. After intravenous administration of aminophylline equivalent to 10 mg kg−1 theophylline, the average mean residence time (MRT) was 58 per cent higher in the protein‐deficient rats, while the total plasma clearance (CI) per kilogram of body weight and elimination rate constant (k) were decreased by 39 per cent and 45 per cent, respectively, when compared to rats on a normal protein diet. No significant difference was found in the two groups of animals with respect to the apparent steady‐state volume of distribution (Vss). The present results suggest that the mechanism responsible for the observed pharmacokinetic changes in the protein‐deficient rats is related to the reduced amount and/or activity of the hepatic mixed function oxidases.
Effect of dietary mineral and vitamin D content and parathyroidectomy on the plasma disappearance rate of 1,25‐dihydroxy vitamin D3 in rats
Authors: Paulson Susan K. , Kenny Alexander D. 
Published: October 2006

AbstractThe plasma disappearance rate of 1,25‐dihydroxyvitamin D3 [1,25‐(OH)2 D3] was determined in rats after a single intravenous injection of the tritiated hormone. Tritiated 1,25‐(OH)2D3 (120 Ci mmol−1) was administered to rats at a dose of 400 000 dpm kg−1 body weight and the animals were bled between 0 and 8 hours. The dose was estimated to produce negligible perturbations in endogenous plasma levels of 1,25‐(OH)2D3. The plasma disappearance of 3H‐1,25‐(OH)2D3 occurred in two phases. The second phase plasma half‐life of 1,25‐(OH)2D3 in immature 25‐ to 35‐day‐old animals (4.7 hours) was significantly shorter than the second phase plasma half‐life of maturing 49‐ to 65‐day‐old animals (8.0 hours). Phosphorus deprivation for 12 days significantly prolonged the second phase plasma half‐life of 1,25‐(OH)2D3 from a control value of 4.9 hours to 10.4 hours. Parathyroidectomy, regardless of the plasma calcium concentrations, shortened the second phase plasma half‐life of 1,25‐(OH)2D3 from control values of 9.1 hours to 5.0 hours. Calcium deprivation for 7 days did not alter the second phase plasma half‐life of 1,25‐(OH)2D3. Vitamin D deprivation for 5 weeks increased the second phase plasma half‐life from 11.0 to 19.9 hours but the difference was not significant.
Pharmacokinetic evaluation of novel sustained‐release dosage forms of valproic acid in humans
Authors: Bialer Meir , Friedman Michael , Dubrovsky Joseph , Raz Itamar , Abramsky Oded 
Published: October 2006

Abstract1. Five new sustained‐release dosage forms of valproic acid (VPA) were developed.2. The new sustained‐release formulations were administered to six healthy subjects for comparison with a standard tablet and an i.v. preparation of the drug.3. Three of the formulations exhibited a more prolonged and uniform absorption rate and yielded more sustained serum levels after ingestion. These three formulations maintained serum therapeutic levels of VPA for 24 h after a single oral administration of 1 g, and were bioequivalent to a marketed standard tablet of VPA.4. The absorption profile of the various oral formulations was analysed pharmacokinetically, using the Loo‐Riegelman procedure.
Oral and rectal nalbuphine bioavailability: First‐pass metabolism in rats and dogs
Authors: Aungst Bruce J. , Lam Gilbert , Shefter Eli 
Published: October 2006

AbstractThe disposition of the narcotic antagonist/analgesic nalbuphine after i.v., oral, and rectal dosing was evaluated in rats and dogs. In both species nalbuphine had high systemic clearance and low oral bioavailability as a result of extensive first‐pass metabolism. Administration to a closed 2 cm length of rectum in rats resulted in complete bioavailability; first‐pass metabolism was circumvented. However, the extent of first‐pass metabolism increased when the dose was not restricted to the lower rectum. Rectal nalbuphine bioavailability in dogs from a solution or three suppository formulations was low and equivalent to oral bioavailability. This was probably because of upward spreading of the dose and subsequent first‐pass metabolism. Sodium salicylate, which has been shown to improve rectal absorption of other drugs, did not affect nalbuphine bioavailability rectally.
Comparative pharmacokinetics of midazolam and loprazolam in healthy subjects after oral administration
Authors: Jochemsen R. , Van Rijn P. A. , Hazelzet T. G. M. , Van Boxtel C. J. , Breimer D. D. 
Published: October 2006

AbstractThe pharmacokinetics of oral midazolam (Dormicum®, 15 mg) and loprazolam (Dormonoct®, 1 mg) were studied in eight healthy young volunteers in a cross‐over design. Plasma concentrations of midazolam were measured with a gas chromatographic method and loprazolam concentrations were determined by a radio‐receptor technique. Absorption of midazolam proceeded very rapidly (median tmax = 0.4 h) and a rapid onset of sedative action was observed. Loprazolam absorption was relatively slow (median tmax = 3 h) and its absorption profile was often irregular. Most subjects fell asleep before peak concentrations were reached. Median peak concentrations were 94 ng ml−1 and 3·1 ng ml−1 for midazolam and loprozolam, respectively. The median elimination half‐life of midazolam was 1·8 h and that of loprazolam 15 h. It is possible that the elimination half‐life of loprazolam as determined by radioreceptor assay is determined by active metabolites rather than by loprazolam itself. Midazolam elimination half‐life was the same when determined by radioreceptor assay or by GLC. There was no significant correlation between the half‐lives of the two drugs.
Novel assay and pharmacokinetics of levamisole and p‐hydroxylevamisole in human plasma and urine
Authors: Kouassi E. , Caillé G. , Léry L. , Larivière L. , Vézina M. 
Published: October 2006

AbstractA new gas chromatographic method was developed for the quantification of levamisole in human plasma and urine, using a nitrogen–phosphorus flame ionization detector. The adsorption of the drug onto glass was prevented by treating the glassware with a siliconizing agent. The sensitivity of the assay was 10 ng ml−1 and as low as 2 ng ml−1 can be detected in plasma.The urinary metabolite p‐hydroxylevamisole was analysed by high performance liquid chromatography with ultraviolet detection. The sensitivity of this assay was 0·50 μg ml−1.Plasma and urinary concentrations of levamisole were determined in 10 healthy volunteers including seven men and three women following the administration of a single 150 mg dose of levamisole. Levamisole was rapidly absorbed (tmax 1·5 h), giving a peak plasma concentration of 716·7 ± 217·5 ng ml−1. The plasma elimination half‐life of levamisole was 5·6 ± 2·5 h. Only 3·2 ± 2·9 per cent of the oral dose was recovered as unchanged drug in the urine, suggesting the importance of clearance of levamisole by routes other than the kidney, and most probably by hepatic metabolism.The urinary concentrations of p‐hydroxylevamisole were determined before and after hydrolysis of the urine samples with β‐glucuronidase, and the level of conjugation of the metabolite with glucuronic acid was then estimated. Cumulative recovery of the metabolite accounted for 1·6 ± 1·1 per cent and 12·4 ± 5.5 per cent of the oral dose of levamisole before and after hydrolysis, respectively, indicating that p‐hydroxylation is a relatively important route of metabolism of levamisole, and that the p‐hydroxylated metabolite is excreted mainly in conjugation with glucuronic acid.Except for the absorption rate of levamisole which is approximately twice as rapid in women as in men, there is no marked difference in the pharmacokinetics of levamisole between healthy men and women.
The non‐linear pharmacokinetics of prednisone and prednisolone. I. Theoretical
Authors: Ferry James J. , Wagner John G. 
Published: October 2006

AbstractThree simple linear and three simple non‐linear pharmacokinetic models are presented which incorporate the reversible metabolism that occurs between prednisone and prednisolone. Under steady‐state conditions it is possible to not only distinguish between the linear and non‐linear models but also to determine which particular model of each group applies to a given set of data. While the non‐linear conversion of prednisolone to prednisone is important in explaining the pharmacokinetics of prednisone in all three non‐linear models, the same is not true for prednisolone.
The pharmacokinetics of exaprolol and propranolol in rats with interrupted enterohepatic circulation
Authors: Motheová O. , Bezek Š. , Ďurišová M. , Faberová V. , Zemánek M. , Mišánikova K. , Trnovec T. 
Published: October 2006

AbstractThe pharmacokinetics of two beta adrenoceptor blocking drugs, exaprolol and propranolol, in rats with interrupted enterohepatic circulation was studied. The tritium‐labelled drugs were given intravenously to four groups of rats: control, bile‐duct cannulated, bile‐duct ligated, and pretreated with neomycin. Plasma levels and excretion were observed up to 96 h after administration. The pharmacokinetic parameters show an enhanced plasma elimination of both drugs at interrupted enterohepatic circulation compared to the control group. Significant changes were observed in the excretion pattern with bile‐duct cannulated and bile‐duct ligated rats, while the total radioactivity excreted in urine and faeces does not differ between control and neomycin pretreated rats.
Intra‐ and intersubject variation of erythromycin absorption from single‐unit and multiple‐unit enteric‐coated products
Authors: Graffner C. , Josefsson K. , Stockman O. 
Published: October 2006

AbstractBased on the in vitro dissolution test for erythromycin capsules introduced in USP XX. Suppl. 3, there are no reasons to expect any difference in bioavailability after administration of two enteric‐coated products, tablets and pellets in hard capsules.The present results in vivo are contradictory and, following duplicate administrations of the two preparations to 12 volunteers after a standardized breakfast, it is apparent that the multiple‐unit, pellets, produce a better reproducibility in absorption both within and between subjects than the single‐unit tablets. All subjects attained measurable levels of erythromycin on all occasions after administration of pellets, while levels were below the detectable limit on six out of the 24 occasions tested after administration of tablets. The better reproducibility of serum levels after pellets than after tablets was also shown in a descriptive way and is given as a low median discrepancy value of 23.5 per cent (moderate) compared to 73.2 per cent (large).
Brain uptake of labelled adiphenine in rats
Authors: Michelot J. , Moreau M. F. , Veyre A. , Labarre P. , Meyniel G. 
Published: October 2006

AbstractThis study describes the behaviour of a dual labelled drug, adiphenine, in the rat brain. Macroautoradiographies show images of the brain at different times after injection. Some of the tissue metabolites are identified at the brain level and the passage of the blood brain barrier is compared with tritiated water.The obtained data give very interesting indications on the blood brain distribution and on the metabolism at the brain level. Different techniques of high pressure liquid chromatography, macro‐ and histoautoradiographies allowed us to visualize how the drug is fixed on cerebral structures, giving indications on its mechanism of action.This fat soluble compound freely crosses the normal blood brain barrier and if labelled with the appropriate emittor could be very useful in nuclear medicine to obtain imaging of the brain.
Bioavailability in man of atenolol and chlorthalidone from a combination formulation
Authors: McAinsh James , Holmes Brian H. , Fitzsimons Timothy J. , Young Jean 
Published: October 2006

AbstractIn this comparative bioavailability study in 12 healthy volunteers the blood level profiles and urinary recoveries of both atenolol and chlorthalidone were studied following the administration of the drugs as a fixed combination (‘Tenoret 50’), as a free combination, and individually, at doses of 50 mg atenolol and 12.5 mg chlorthalidone.There were no statistically or clinically significant differences between the three treatments of atenolol in terms of individual blood levels, areas under the curve, and urinary excretion. The mean half‐lives were between 5 and 7h, in agreement with other published data. The variation in peak systemic levels is less than that observed for a number of other β‐blocking drugs and is of the same order as seen in other investigations involving atenolol. Thus the bioavailability of atenolol from the fixed combination is equivalent to that from the free combination and from the atenolol tablet.The mean peak blood concentrations of chlorthalidone were 0.94, 1.00, and 0.99 μg ml−1 for the fixed and free combinations and the chlorthalidone tablet, respectively. The mean areas under the curve were also similar as were the mean half‐lives and urinary recovery. There were no statistically or clinically significant differences between the three treatments. Thus the bioavailability of chlorthalidone from the fixed combination is equivalent to that from the free combination and from the chlorthalidone tablet.It is concluded that combining chlorthalidone and atenolol in a single tablet does not affect the systemic bioavailability of either component.
Pharmacokinetics, metabolism and renal excretion of sulfatroxazole and its 5‐hydroxy‐ and N4‐acetylmetabolites in man
Authors: Vree T. B. , Vree T. B. , Hekster Y. A. , Tijhuis M. W. , Termond E. F. S. , Nouws J. F. M. 
Published: October 2006

AbstractHydroxylation is the predominant pathway of metabolism for sulfatroxazole in the body, accounting for 70 per cent of the dose. Fifteen per cent of the dose is acetylated unimodally and 10 per cent is excreted unchanged. The half‐lives of sulfatroxazole and its metabolites 5‐hydroxysulfatroxazole and N4‐acetylsulfatroxazole are approximately 22 h after administration of sulfatroxazole. N4‐acetylsulfatroxazole, taken as parent drug, is eliminated by renal excretion (92 per cent of the dose). The initial elimination half‐life of N4‐acetylsulfatroxazole is 4.5 h, which later increases to 70 h as the result of the acetylation‐deacetylation equilibrium. Probenecid inhibits the renal excretion of the metabolites 5‐hydroxy‐ and N4‐acetylsulfatroxazole. Inhibition of the N4‐acetylmetabolite favours the deacetylation, which results in an increase of the T1/2 of sulfatroxazole from 20 to 30 h. The protein binding value of sulfatroxazole is 84 per cent, that of N4‐acetylsulfatroxazole is 37 per cent. Sulfatroxazole is excreted renally by passive processes, while the metabolites are excreted by both passive and active processes.