bluuebunny/crossref_metadata_2025_split huggingface dataset:
Ceftriaxone pharmacokinetics in elderly subjects and penetration into epididymis
Authors: Geny Florence , Costa Pierre , Bressolle Francoise , Galtier Marc 
Published: October 2006

AbstractIn a prospective study, the epididymal penetration of ceftriaxone was evaluated in order to use it in the treatment of orchi‐epididymitis in men. A bolus intravenous dose of 1 g of ceftriaxone was administered to 15 patients hospitalized for surgery as part of treatment for prostatic adenoma or prostatic cancer. Nine successive blood samples were collected in the interval from 0 to 24 h after administration, and epididymis samples were taken 0.75 h after administration. Concentrations of drug in all samples were assayed by a reverse‐phase‐ion pairing high‐performance liquid chromatography method with UV detection. The results showed that the pharmacokinetics of ceftriaxone in serum did not differ from those determined previously in healthy volunteers. The terminal half‐life was 6.9 ± 1.7 h, and the mean residence time 9.5 ±2.3 h. The volume of distribution was 0.144 ± 0.018 1 kg−1 and the total body clearance 1.17 ± 0.29 1 h−1. The concentrations in tissue reached 27.2 ± 6μg g−1 in right epididymis, and 25.4 ± 6.2 μg g−1 in left epididymis. The tissue‐versus‐serum concentration ratios ranged from 0.175 to 0.545 (mean value, 0.295 ± 0.099). The concentrations in serum and tissue observed in this study were in excess of the MICs for bacteria considered to be susceptible to ceftriaxone, particularly Neisseria gonorrhea and coliform bacteria.
Biopharmaceutical evaluation of transnasal, sublingual, and buccal disk dosage forms of butorphanol
Authors: Shyu Wen Chyi , Mayol Robert F. , Pfeffer Morris , Pittman Kenneth A. , Gammans Richard E. , Barbhaiya Rashmi H. 
Published: October 2006

AbstractA series of three‐way crossover randomized studies were conducted to evaluate the absolute bioavailability of butorphanol, a potent agonist‐antagonist analgesic, from transnasal, sublingual, and buccal disk formulations in order to identify a practical alternative to oral administration. In each study, healthy male volunteers received 2 mg doses of butorphanol tartrate intravenously and either transnasally, sublingually or buccally. Serial blood samples were collected over 12 h and butorphanol plasma concentrations were determined by radioimmunoassay. The plasma concentration data were subjected to non‐compartmental pharmacokinetic analysis. The elimination half‐life of butorphanol was about 3–5 h and was independent of the route of administration. Absorption of butorphanol following transnasal administration was faster than that observed following sublingual or buccal administration. Mean absolute bioavailabilities of sublingual tablet and buccal disk formulation were only 19 per cent and 29 per cent, respectively, but for transnasal administration the value rose significantly, to 70 per cent. Based on the results of these studies, transnasal dosage form of butorphanol was selected for further clinical trials of treatment of moderate to severe pain.
Pharmacokinetics of diacerein in patients with liver cirrhosis
Authors: Magnard O. , Louchahi K. , Tod M. , Petitjean O. , Molinier P. , Berdah L. , Perret G. 
Published: October 2006

AbstractThe pharmacokinetics of diacerein following a single oral dose of 50 mg was studied in 12 healthy volunteers, 10 patients with a mild liver cirrhosis (Child Pugh's grade A), and 6 patients with a more severe liver cirrhosis (Child Pugh's grade B to C). Statistical analysis using a Kruskal‐ Wallis test showed no significant differences between the three groups for the following parameters: median Cmax was 3.9 mg l−1 for the cirrhotic patients group I (CPI) and 3.2 mg l−1 for the cirrhotic patients group II (CPII) versus 3.2 mg l−1 for the healthy volunteers (HV); median t1/2 was 4.9 h for CPI and 4.3 h for CPII versus 4.3 h for HV; median Cl/F was 2.1 l h−1 for CPI and 2.5 l h−1 for CPII versus 1.6 l h−1 for HV; median Vdss/F was 12.6 l for CPI and 14.01 for CPII versus 13.2 l for HV. The urinary parameters were comparable. It was concluded that, from a pharmacokinetic point of view, no reduction in the initial dosage of diacerein need be proposed in liver cirrhosis.
Relative bioavailability of two disopyramide capsules in humans based on total, unbound, and unbound enantiomer concentrations
Authors: Takahashi Harumi , Ogata Hiroyasu , Shimizu Mikiko , Hashimoto Kayoko , Masuhara Keiso , Kashiwada Kazuko , Someya Kazuhiko 
Published: October 2006

AbstractThe relative bioavailability of two 100‐mg disopyramide formulations which showed almost an 8‐ to 10‐fold difference in their dissolution rates at pH 1.2 and 6.8 was determined in eight healthy subjects using a randomized block design. Although no significant differences in relative bioavailability were observed between the two formulations when based on the total disopyramide concentration, an almost 30 per cent difference in the extent of bioavailability was observed when assessed in terms of the unbound (±)‐ and (−)‐disopyramide concentration, due probably to stereoselective nonlinear plasma protein binding. This suggests that unbound enantiomer parameters would be more sensitive to differences in bioavailability between two disopyramide formulations. Therefore, the type of concentration used would be an important factor for precise evaluation of the relative bioavailability of racemic drugs.
Bioavailability of intramuscularly administered tenoxicam
Authors: Stebler T. , Guentert T. W. 
Published: October 2006

AbstractBioavailability of intramuscularly administered tenoxicam relative to single oral and relative to intravenous doses was determined in two separate randomized crossover studies. Twelve healthy volunteers (12 males, age 20–30 years) received a rapid intravenous injection and a single intramuscular dose and 12 other subjects (11 males, 1 female, age 21–25 years) a single oral and a single intramuscular dose of 20 mg of tenoxicam on two different occasions. The wash‐out period between the two consecutive treatments was 4 weeks. Plasma concentrations after dosing were determined by a specific HPLC method.Differences in tenoxicam concentration‐time profiles after the different routes of administration were limited to the first 2 h after dosing. Later, plasma concentrations were almost superimposable within and across the two studies. The extent of absorption of intramuscularly administered tenoxicam was complete (mean ± CV per cent: Fabs 0.99 ± 20 per cent) with no difference between the two extravascular administrations (Frel 0.95 ± 10 per cent, intramuscular vs oral). After intramuscular administration tenoxicam was more rapidly absorbed compared to the oral dose (Tmax 0.71 h ± 80 per cent vs 1.4 h ± 62 per cent; p>0.05). Peak concentrations after oral and intramuscular administration (Cmax 2.5 mg 1−1 ± 19 per cent vs 2.7 mg l−1 14 per cent; p <0.05) were very similar.
Stereospecific evaluation of sotalol pharmacokinetics in a rat model: Evidence suggesting an enantiomeric interaction
Authors: Carr R. A. , Pasutto F. M. , Foster R. T. 
Published: October 2006

AbstractSotalol (STL) is a chiral β‐adrenergic blocking drug, which is useful clinically as the racemate in treating hypertension, and is also useful as a class III antiarrhythmic when administered as the pure S‐enantiomer. Utilizing a stereospecific high‐performance liquid chromatographic (HPLC) assay, the enantiomeric disposition of STL is reported after administration of racemate and both pure enantiomers to a rat model. After administration of the racemate, enantiomers of STL had similar plasma concentration‐time profiles. Following administration of the pure S‐enantiomer of STL, however, systemic clearance was significantly reduced; R‐STL disposition after pure enantiomer administration was not significantly altered. Changes in systemic clearance of S‐STL after either racemate or enantiomer dosing were explained by corresponding changes in renal clearance. Renal clearance values of S‐STL were significantly reduced from 33·7 ± 6·0 to 28·9 ± 5·6 ml min−1 kg−1 for administration as racemate and pure enantiomer, respectively. As clearance of STL approximates reported values of renal blood flow, renal perfusion changes caused by the β‐blocking effects of R‐STL may explain changes in S‐STL disposition. It is suggested that dosing of STL as either racemate or pure enantiomer, depending on the clinical indication for use, may result in significantly altered enantiomer disposition.
Intestinal absorption pathway of γ‐aminobutyric acid in rat small intestine
Authors: Nácher A. , Polache A. , Moll‐Navarro M. J. , Plá‐Delfina J. M. , Merino M. 
Published: October 2006

AbstractIntestinal absorption of γ‐aminobutyric acid (GABA), as a model compound for γ‐aminoacids, has not been extensively studied from the kinetic viewpoint. Since data from our laboratory suggested that some competition arises between intestinal absorption of β‐alanine and GABA and since our intent was to maintain the aqueous stagnant diffusion layer in order to approach absorption tests to in vivo physiological conditions, a rat jejunum in situ study was undertaken in order to gain an insight into the mechanism of GABA absorption. In the present paper, results from assays using isotonic perfusion solutions with starting GABA concentrations ranging from 1 to 50 mM are reported. They show that the intestinal absorption of the γ‐aminoacid can be apparently described as a specialized transport mechanism which obeys Michaelis‐Menten and first‐order kinetics. Parameter values found were Vm = 13.99 ± 2.37 mM h−1, Km = 3.87 ± 0.63 mM, and ka(passive) = 0.362 ± 0.120 h−1. Through the perfusion of 5 mM β‐alanine solutions containing variable concentrations of GABA (from 5 to 50 mM), a partially competitive inhibition of β‐alanine absorption was apparently characterized.
Effects of benidipine hydrochloride (Coniel®), a new calcium antagonist, on the cardiac output, regional blood flow and vascular resistance in conscious, spontaneously hypertensive rats
Authors: Harashima Hideyoshi , Kiwada Hiroshi , Kajita Jirou , Kobayashi Satoshi 
Published: October 2006

AbstractBenidipine hydrochloride is a calcium antagonist with a 1,4‐dihydropyridine derivative structure, and exhibits long‐lasting antihypertensive effects by inhibiting the voltagedependent Ca2+ channels. This study was undertaken to examine the effect of benidipine on central haemodynamics and regional blood flow (RBF) after intravenous administration of benidipine in conscious, spontaneously hypertensive rats. The microsphere method was used to measure cardiac output and RBF before and after the drug administration, using microspheres labelled with 57Co and 51Cr. Thirty minutes after the intravenous administration of benidipine (3 μg kg−1), the mean arterial pressure fell by 15% without significantly increasing the heart rate. The cardiac output increased by 41% and the systemic resistance decreased by 39%. Benidipine significantly increased RBF by 37,35, and 22% in kidney, heart, and small intestine, respectively, and decreased vascular resistance by 38, 38, and 32%, respectively. We concluded that benidipine reduced blood pressure by increasing RBF in the kidney and heart, while keeping RBF in other organs at a normal level. These results will provide a fundamental basis in support of the clinical benefits of benidipine for hypertensive patients, particularly those with renal failure.
The effect of colestipol and cholestyramine on ibuprofen bioavailability in man
Authors: Al‐Meshal Mohamed A. , El‐Sayed Yousry M. , Al‐Balla Sulaiman R. , Gouda M. Wafik 
Published: October 2006

AbstractThe purpose of this study was to determine whether a concomitant single oral dose of one of the anion exchange resins colestipol hydrochloride (10 g) or cholestyramine (8 g) administered with ibuprofen (400 mg) would alter the bioavailability of this non‐steroidal anti‐inflammatory agent. The study was performed according to a randomized three‐way crossover design in six healthy male volunteers. After dosing, serial blood samples were collected for a period of 10 h. Plasma harvested from blood was analysed for ibuprofen by a sensitive high‐performance liquid chromatographic method. There were no significant differences between colestipol treatment and control for peak plasma concentration (Cmax), time to peak concentration (Tmax), area under the plasma concentration—time curve (AUC), mean residence time (MRT), elimination rate constant (Kel), or elimination half‐life (t1/2). Cholestyramine treatment resulted in a significant decrease in AUC (26%, p< 0.05) and Cmax (34.4%, p <0.01) and a significant increase in Tmax (80%, p < 0.01) and MRT (20.2%, p < 0.05). Cholestyramine administration showed no significant effect on the Kel and t1/2 values. A significant correlation was obtained between the increase in MRT and the increase in Tmax. The confidence intervals (90%) of the mean values of the pharmacokinetic parameters (AUCO–∞ and Cmax) for the colestipol : control ratio were well within the acceptable range of 100 ± 20, whereas those for the cholestyramine : control ratio were outside it. Colestipol treatment was found to be bioequivalent to the control treatment by Schuirmann's two one‐sided t tests, while cholestyramine treatment was found to be bioinequivalent. The results indicate a lack of interaction between ibuprofen and colestipol and a potential significant interaction (decrease in rate and extent of absorption of ibuprofen) between cholestyramine and ibuprofen in patients receiving concurrent therapy.
Bioequivalence of pyrantel pamoate dosage forms in healthy human subjects
Authors: Fasanmade Adedigbo A. , Akanni Abraham O. , Olaniyi Ajibola A. , Fasanmade Adesoji A. , Tayo Fola 
Published: October 2006

AbstractDrugs that are largely restricted to the gastro‐intestinal tract (GIT) for their therapeutic efficacy and that are not substantially absorbed into the body are usually inadequately studied in terms of systemic bioavailability. The possibility of systemic effects requires that bioavailabilities be studied to ensure against enhanced toxicity resulting from formulation differences. Pyrantel pamoate falls into this category. High‐performance liquid chromatography was employed in this study to determine plasma levels of pyrantel in nine healthy human subjects after administration of tablet and suspension dosage forms. Mean peak plasma concentrations of 37.56 ± 9.37, 35.89 ± 8.94, and 36.22 ± 10.10 ng mL−1 were obtained following administration of 750 mg pyrantel pamoate in three different formulations. The mean tmax values were 2.02 ± 0.12, 2.05 ± 0.356, and 2.05 ± 0.339 h respectively for the above dosage forms; the respective AUC0–9 values were 81.01 ± 12.97, 94.59 ± 17.18, and 101.47 ± 19.59 h ng mL−1. There was no statistically significant difference between the bioavailabilities of the dosage forms tested. Large inter‐subject variations were observed. One subject experienced abdominal discomfort and one experienced dizziness. It was not possible to clearly correlate individual variations in absorption with the observed adverse effect because the number of incidents was low (two out of 27 treatments).
The effect of competitive and non‐linear plasma protein binding on the stereoselective disposition and metabolic inversion of ibuprofen in healthy subjects
Authors: Smith David E. , Paliwal Jyoti K. , Cox Steven R. , Berardi Rosemary R. , Dunn‐Kucharski Valerie A. , Elta Grace H. 
Published: October 2006

AbstractThe stereoselective disposition and metabolic inversion of ibuprofen were studied in 12 healthy subjects under conditions of competitive and non‐linear plasma protein binding. Each subject received each of four oral treatments according to a Latin‐square design: 300 mg R(−)‐ibuprofen, 300 mg S(+)‐ibuprofen, 300 mg R(−)‐ + 300mg S(+)‐ibuprofen, and 300 mg R(−)‐ + 600 mg S(+)‐ibuprofen. For a given treatment, the partial clearance of S(+)‐ibuprofen was greater than that of R(−)‐ibuprofen for all stereoisomeric drug species. Likewise, the unbound partial clearances of S(+)‐ibuprofen were greater for most stereoisomeric drug species. There was also less difference among treatment groups when partial clearances were referenced to unbound as opposed to total plasma concentrations of enantiomer. The unbound intrinsic clearance and fractional inversion of R(−)‐ibuprofen were unchanged across the four treatments, and chiral inversion was systemic, averaging 69%. In conclusion, stereoselective differences exist for the partial and composite clearances of R(−)‐ and S(+)‐ibuprofen even when corrected for differences in plasma protein binding. However, differences among treatment groups for a particular elimination pathway are largely due to ibuprofen's non‐linear binding.
Repeated dose pharmacokinetics of pancopride in human volunteers
Authors: Salva P. , Costa J. , Perez‐Campos A. , Martinez‐Tobed A. 
Published: October 2006

AbstractThe aim of this study was to assess the pharmacokinetic profile of pancopride after repeated oral dose administration of 20 mg pancopride in tablet form once a day for 5 d in 12 healthy male volunteers. Plasma levels were measured by HPLC using a solid phase extraction method and automated injection. The minimum quantification limit of pancopride in plasma was 2 ng mL−1. The maximum plasma concentration (mean ± SD) after the first dose was 92.5 ± 41.5 ng mL−1 and tmax was 1.7 ± 0.9 h. The elimination half‐life (t1/2) was 14.3 ± 6.9 h. The area under the concentration‐time curve from zero to infinity (AUC) was 997 ± 396 ng h mL−1. The maximum plasma concentration (mean ± SD) at steady state (day 5) was 101.8 ± 36.9 ng mL−1 and tmax was 2.2 ± 1.2 h. The elimination half‐life (t1/2) was 16.3 ± 2.7 h and the minimum plasma concentration (C) was 16.6 ± 6.9 ng mL−1. The area under the concentration‐time curve during the dosing interval (AUC) was 995 ± 389 ng h mL−1. The average plasma concentration at steady state (C) was 43.3 ± 16.1 ng mL−1 and the experimental accumulation ratio (RAUC) was 1.34 ± 0.19, whereas the mean theoretical value (R) was 1.40 ± 0.29. The results obtained showed a good correlation between the experimental plasma levels and the expected values calculated using a repeated dose two‐compartment model assessed by means of the Akaike value. It is concluded that the pharmacokinetics of pancopride are not modified after repeated dose administration. The safety parameters showed no clinically relevant alterations.
The pharmacokinetics and absolute bioavailability of selegiline in the dog
Authors: Mahmood Iftekhar , Peters David K. , Mason William D. 
Published: October 2006

AbstractSelegiline is beneficial to Parkinsonian patients as an adjunct to levodopa therapy. Currently no pharmacokinetic data are available for selegiline in the literature, mainly due to lack of analytical methods that can measure concentrations below 10 ng mL−1 in plasma. A sensitive fluorimetric assay based on inhibition of rat brain monoamine oxidase‐B (MAO‐B) in vitro has been developed to measure selegiline in plasma as low as 0.25 ng mL−1. The pharmacokinetics of selegiline were investigated following intravenous and oral administration to four female mongrel dogs. Each dog received 1 mg kg−1 selegiline in solution via gavage or by an intravenous route separated by one week. The mean terminal half‐life, volume of distribution of the central compartment, and systemic clearance of selegiline were 60.24 ± 9.56 min, 6.56 ± 0.56 L kg−1, and 159.91 ± 19.28 mL min−1 kg−1, respectively. After oral administration selegiline appeared to be absorbed rapidly with a tmax and Cmax of 25 ± 5.8 min and 5.2 ± 1.36 ng mL−1, respectively. The absolute bioavailability of selegiline in the dog was 8.51 ± 3.31%.
The relationship between pharmacokinetic behaviour of glycyrrhizin and hepatic function in patients with acute hepatitis and liver cirrhosis
Authors: Yamamura Yoshikazu , Tanaka Naomi , Santa Tomofumi , Kotaki Hajime , Aikawa Tatsuya , Uchino Katsuyoshi , Osuga Toshiaki , Sawada Yasufumi , Iga Tatsuji 
Published: October 2006

AbstractThe pharmacokinetic behavior of glycyrrhizin in four patients with acute hepatitis (hepatitis group) and six patients with liver cirrhosis (cirrhosis group) receiving chronically an IV administration of a 120 mg dose once a day or once every other day of glycyrrhizin was investigated. The plasma concentration of glycyrrhizin declined monoexponentially in both groups. The elimination half‐life (t1/2) for glycyrrhizin in the hepatitis and cirrhosis groups varied significantly in the range of 2.7–7.6 h and 6.2–40.1 h, and the total body clearance (CLtot) in the range of 2.8–23.2 mL h−1 kg−1 and 1.4–12.9 mL h−1 kg−1, respectively. The t1/2 for glycyrrhizin in the hepatitis and the cirrhosis groups was about twice and eight times that in normal subjects, respectively, as reported previously, and CLtot values were about 0.7 and 0.23 times that in normal subjects, respectively. There was significant correlation between the CLtot and hepatic function (asparatate aminotransferase and alanine aminotransferase in serum) in both patient groups. With improvement of the liver function, the CLtot for glycyrrhizin increased from 2.8 ml h−1 kg−1 to 11.4 mL h−1 kg−1, and the t1/2 shortened from 7.6 h to 3.4 h. These findings indicated that the variation of pharmacokinetic behaviour of glycyrrhizin in both groups was closely related to the extent of the liver function.
The bioavailability of cefpodoxime proxetil tablets relative to an oral solution
Authors: Borin Marie T. , Forbes Kristi K. , Hughes George S. 
Published: October 2006

AbstractThe bioavailability of cefpodoxime proxetil tablets relative to an oral solution of cefpodoxime proxetil in a sucrose/alcohol/citric acid vehicle was studied in 11 healthy volunteers in a randomized, crossover study. Fasted subjects took one cefpodoxime proxetil 100 mg tablet or 50 mL of a 2 mg mL−1 cefpodoxime proxetil oral solution on two separate occasions. In a third study period, all subjects took a 100 mg dose of the oral solution with a high‐fat meal to investigate the effect of food on cefpodoxime proxetil absorption from the oral solution. Serial blood samples were obtained over a 24h period, and urine was collected for 48h after dosing. Cefpodoxime concentrations in plasma and in urine were determined using HPLC methods. The bioavailability of cefpodoxime proxetil tablets relative to the oral solution was 82%, as determined from AUC ratios. There was no difference in the rate of cefpodoxime absorption between dosage forms. Food had no effect on the extent of drug absorption from the oral solution but did result in delayed absorption. These results suggest that complete dissolution of cefpodoxime proxetil is critical for optimal bioavailability.