ALBERT — All Library Books, journals and Electronic Records Telegrafenberg

1

Electronic Resource

Human Transbuccal Absorption of Diclofenac Sodium from a Prototype Hydrogel Delivery Device (1993)

Cassidy, James ; Berner, Bret ; Chan, Keith ; [et al.]

Springer

Pharmaceutical research 10 (1993), S. 126-129

add to mindlist on the mindlist

Details

ISSN: 1573-904X

Keywords: buccal delivery ; diclofenac sodium ; human clinical ; hydrogel device

Source: Springer Online Journal Archives 1860-2000

Topics: Chemistry and Pharmacology

Notes: Abstract The buccal delivery of the nonsteroidal antiinflammatory drug, diclofenac sodium (Voltaren), from a prototype hydrogel was studied in man in a randomized crossover design of buccal delivery and i.v. infusion. After a 30-min delay, plasma levels of diclofenac increased to near steady-state levels of 100 ng/ml by 3 hr. With each subject serving as his own control, the i.v. infusion data facilitated the calculation of a mean steady-state flux of diclofenac sodium of 2.1 ± 0.6 mg/cm2-hr across human buccal mucosa and a time lag of 1.0 ± 0.5 hr. The large flux of this ionized species indicates that the traditional lipoidal model of buccal permeation based on the partition coefficient is inadequate.

Type of Medium: Electronic Resource

URL: http://dx.doi.org/10.1023/A:1018941517355

Permalink

	Location	Call Number	Expected	Availability

Others were also interested in ...

Paper (German National Licenses)

Fulltext

2

Electronic Resource

Site-Differential Gastrointestinal Absorption of Benazepril Hydrochloride in Healthy Volunteers (1994)

Chan, Keith K. H. ; Buch, Akshay ; Glazer, Robert D. ; [et al.]

Springer

Pharmaceutical research 11 (1994), S. 432-437

add to mindlist on the mindlist

Details

ISSN: 1573-904X

Keywords: site-differential absorption ; gastrointestinal intubation ; benazepril ; benazeprilat ; angiotensin-converting enzyme (ACE) inhibitor

Source: Springer Online Journal Archives 1860-2000

Topics: Chemistry and Pharmacology

Notes: Abstract The absorption of benazepril-HCl (BZPH), an orally active angiotensin-converting enzyme (ACE) inhibitor, in various regions of the gastrointestinal (GI) tract was investigated using an intestinal intubation technique. Thirteen subjects completed this single-dose, three-phase sequential crossover study. The drug (20 mg) was administered either as a 4-hr colonic infusion (COLON) or as a small intestinal infusion (SI) in the first two phases and as an oral bolus solution (ORAL) in the third phase, with a 2-week washout between each treatment. Serial plasma and urine samples were collected for up to 4 days after dosing. BZPH and its active metabolite benazeprilat (BZPL) were determined using a gas chromatography/mass spectrometry method. BZPH was absorbed rapidly into the bloodstream (T max = 0.5 hr after ORAL). Absorption was also rapid for SI, with a postinfusion half-life (0.57 hr) nearly identical to that for ORAL (0.59 hr). The absorption rate after COLON was much slower (lower C max and longer T max) compared to that after SI, and the apparent half-life (1.7 hr) was prolonged. SI delivered 90%, whereas COLON delivered 23%, of the drug into the systematic circulation as compared to ORAL. BZPL was rapidly formed upon drug absorption. The metabolite-to-drug AUC ratios were comparable for SI and ORAL (8.9 vs 9.7), indicating that first-pass metabolism of BZPH was neither saturable nor input rate dependent. The metabolite-to-drug AUC ratio was reduced for COLON (5.0), indicating that the mechanism of absorption of BZPH in the colon may be different than that after SI and ORAL. Urinary recovery data were consistent with plasma data. It can be concluded that COLON delivered a smaller amount of drug at a slower absorption rate to the body than either SI or ORAL.

Type of Medium: Electronic Resource

URL: http://dx.doi.org/10.1023/A:1018925407109

Permalink

	Location	Call Number	Expected	Availability

Others were also interested in ...

Paper (German National Licenses)

Fulltext

3

Electronic Resource

Intra- and Inter-Subject Variabilities of CGP 33101 after Replicate Single Oral Doses of Two 200-mg Tablets and 400-mg Suspension (1995)

Cheung, Wing K. ; Kianifard, Farid ; Wong, Audrey ; [et al.]

Springer

Pharmaceutical research 12 (1995), S. 1878-1882

add to mindlist on the mindlist

Details

ISSN: 1573-904X

Keywords: CGP 33101, intra-subject variability ; inter-subject variability ; pharmacokinetics ; healthy subjects ; bioavailability

Source: Springer Online Journal Archives 1860-2000

Topics: Chemistry and Pharmacology

Notes: Abstract Purpose. The purpose of this study was to use a replicate designed trial to assess the overall, intra- and inter-subject variabilities in pharmacokinetic parameters of CGP 33101 after oral administration of tablets relative to that of powder suspended in water, and to determine the relative proportion of the intra-subject variance to the overall variability. Methods. Sixteen healthy subjects were randomly assigned to four groups to receive tablets and suspension twice in four different treatment sequences. The plasma concentration-time profile of CGP 33101 was characterized in terms of Cmax, Tmax, and AUC. Bioavailability of tablets relative to suspension and intra- and inter-subject variability were assessed by statistical analysis. Results and Conclusions. The overall variabilities in absorption kinetics of CGP 33101 in healthy subjects were small with CV's of the population mean values for AUC and Cmax less than 26% for both tablets and suspension. Contribution of intra-subject variability to the overall variability was also small (~20%). Both the overall and intra-subject variabilities of AUC and Cmax after suspension were larger than after the tablets. However, the differences in variability between tablets and suspension were not statistically significant (p 〉 0.05). The tablet formulation was bioequivalent to suspension in terms of rate and extent of absorption based on 90% conventional confidence intervals (for AUC and Cmax) and Wilcoxon rank-sum test (for Tmax).

Type of Medium: Electronic Resource

URL: http://dx.doi.org/10.1023/A:1016275402723

Permalink

	Location	Call Number	Expected	Availability

Others were also interested in ...

Paper (German National Licenses)

Fulltext

4

Electronic Resource

Intra- and Intersubject Variability: Mixed-Effects Statistical Analysis of Repeated Doses of an Angiotensin Converting Enzyme Inhibitor, CGS 16617 (1989)

Kochak, Gregory M. ; Smith, Robert A. ; Choi, R. Leslie ; [et al.]

Springer

Pharmaceutical research 6 (1989), S. 328-331

add to mindlist on the mindlist

Details

ISSN: 1573-904X

Keywords: random-effects statistical model ; bioavailability trials ; biological variation ; intersubject variability ; intrasubject variability ; CGS 16617

Source: Springer Online Journal Archives 1860-2000

Topics: Chemistry and Pharmacology

Notes: Abstract The intrasubject and intersubject variabilities for CGS 16617, an angiotensin converting enzyme inhibitor, were evaluated in an open-label, repeat single-dose bioavailability trial. Eight healthy male volunteers each received a 20-mg oral dose of CGS 16617 as an aqueous solution on four separate occasions. Components of variance were evaluated for a mixed-effects statistical model in which subjects were regarded as a random factor. While intersubject variability was statistically significant (P 〈 0.05) for all pharmacokinetic variables measured, AUC, C max, t 1/2, and t max, its contribution to the total observed variability was relatively small for AUC, t 1/2 and t max. The proportion of variation due to intrasubject variability was 70, 19, 61, and 72% for AUC, C max, t 1/2, and t max, respectively. Ramifications of the large intrasubject source component of variability as related to bioavailability trials and biological variation are discussed.

Type of Medium: Electronic Resource

URL: http://dx.doi.org/10.1023/A:1015954609527

Permalink

	Location	Call Number	Expected	Availability

Others were also interested in ...

Paper (German National Licenses)

Fulltext

5

Electronic Resource

Application of Radiotelemetric Technique in Evaluating Diclofenac Sodium Absorption After Oral Administration of Various Dosage Forms in Healthy Volunteers (1990)

Chan, Keith K. H. ; Mojaverian, Parviz ; Ziehmer, Barbara A. ; [et al.]

Springer

Pharmaceutical research 7 (1990), S. 1026-1032

add to mindlist on the mindlist

Details

ISSN: 1573-904X

Keywords: radiotelemetric technique ; diclofenac sodium ; absorption ; enteric-coated tablet ; slow-release tablet ; buffered aqueous solution ; multiple peak behavior

Source: Springer Online Journal Archives 1860-2000

Topics: Chemistry and Pharmacology

Notes: Abstract A radiotelemetric technique with the Heidelberg capsule (HC) was used to improve the quality of data generated in a bioavailability study involving an enteric-coated (EC) formulation. Further, changes in plasma levels of the drug from other dosage forms were related to changes in the pH environment as determined by the HC. Eight healthy male subjects received the following treatments, 15 min after a light breakfast, according to a randomized, four-way crossover design: (A) HC and 75 mg of a diclofenac sodium aqueous buffered solution; (B) HC and one 75-mg Voltaren EC tablet; (C) HC and one 100-mg Voltaren slow-release (SR) tablet; and (D) HC alone. Each treatment was separated by a 1-week washout period. Two additional subjects subsequently received Treatment B only. Multiple peaks were observed in the drug plasma level–time profiles for the buffered aqueous solution which, in all cases, occurred before gastric emptying of the HC. The multiple peaks were not observed for the Voltaren SR tablet, but a variable absorption lag time occurred which coincided with the gastric residence time of the SR tablet. For the EC tablet the variability of individual plasma level–time profiles was drastically reduced when the time after dosing was adjusted to coincide with gastric emptying of the HC. Finally, the lag time between gastric emptying of the EC tablet and the onset of drug absorption was consistently at 1 hr for all subjects. This lag time was longer than the in vitro disintegration or dissolution times measured under USP conditions.

Type of Medium: Electronic Resource

URL: http://dx.doi.org/10.1023/A:1015987016003

Permalink

	Location	Call Number	Expected	Availability

Others were also interested in ...

Paper (German National Licenses)

Fulltext

6

Electronic Resource

Nitroglycerin Absorption from Transdermal Systems: Formulation Effects and Metabolite Concentrations (1991)

Williams, Roger L. ; Thakker, Kamlesh M. ; John, Vivian ; [et al.]

Springer

Pharmaceutical research 8 (1991), S. 744-749

add to mindlist on the mindlist

Details

ISSN: 1573-904X

Keywords: nitroglycerin ; nitroglycerin metabolites ; bioequivalence ; transdermal drug delivery

Source: Springer Online Journal Archives 1860-2000

Topics: Chemistry and Pharmacology

Notes: Abstract We recently compared plasma concentrations of nitroglycerin and its two dinitrate metabolites in 16 healthy male subjects after application of two controlled-release transdermal formulations of the drug. Analysis of the resulting plasma concentration–time curves indicated that the two formulations did not produce equivalent concentrations of parent drug or either of the dinitrate metabolites during the initial period of dosing. In addition, both formulations produced concentrations of the two dinitrate metabolites that exceeded the concentration of the parent drug by severalfold. Even if the pharmacologic effect of the dinitrate metabolites is low compared to that of nitroglycerin, these higher concentrations may contribute to the effect of nitroglycerin. Scrutiny of the ratio of 1,2-glyceryl dinitrate to 1,3-glyceryl dinitrate in the 16 subjects confirmed previous observations that preferential formation of the 1,2-glycerol dinitrate metabolite may occur depending on the route of administration. This ratio may thus be indicative of the bioavailability of nitroglycerin following transdermal application. Additional data suggesting racial differences in nitroglycerin absorption after transdermal application are presented.

Type of Medium: Electronic Resource

URL: http://dx.doi.org/10.1023/A:1015802101272

Permalink

	Location	Call Number	Expected	Availability

Others were also interested in ...

Paper (German National Licenses)

Fulltext

7

Electronic Resource

Pharmacokinetics of Multiple Daily Transdermal Doses of Nicotine in Healthy Smokers (1991)

Ross, Holly D. ; Chan, Keith K. H. ; Piraino, Anthony J. ; [et al.]

Springer

Pharmaceutical research 8 (1991), S. 385-388

add to mindlist on the mindlist

Details

ISSN: 1573-904X

Keywords: nicotine ; cotinine ; pharmacokinetics ; multiple dose ; transdermal delivery

Source: Springer Online Journal Archives 1860-2000

Topics: Chemistry and Pharmacology

Notes: Abstract The plasma concentration–time profiles and pharmacokinetics were characterized for nicotine and its major metabolite, cotinine, after multiple daily application of a nicotine user-activated transdermal therapeutic system (UATTS) to nine healthy smokers. The volunteers abstained from smoking 24 hr prior to and during the course of the study. A 10-cm2 system (designed to deliver 75 µg/cm2/hr) was applied every 24 hr for 5 days, with serial blood samples taken on Days 1 and 5 and after system removal on Day 5. Generally, the nicotine UATTS was well tolerated. Predose nicotine concentrations on Days 3 to 5 indicated that steady state was reached by Day 3. The nicotine pharmacokinetic parameters for Day 1 and Day 5 were similar: the mean (SD) AUC(0-24) values for Days 1 and 5 were 271.7 (50.7) and 311.7 (55.0) ng · hr/ml, the mean (SD) C max values were 16.3 (2.6) and 16.8 (2.9) ng/ml, and the median (range) T max values on Days 1 and 5 were 12 (9–24) hr and 12 (0–24) hr, respectively. There was only slight or no accumulation of nicotine after multiple dosing as indicated by the Day 5 to Day 1 AUC and C max ratios of 1.15 (0.09) and 0.98 (0.06), respectively. Overall, the UATTS system maintained relatively constant plasma nicotine concentrations and is suitable for once-daily application.

Type of Medium: Electronic Resource

URL: http://dx.doi.org/10.1023/A:1015810019076

Permalink

	Location	Call Number	Expected	Availability

Others were also interested in ...

Paper (German National Licenses)

Fulltext

8

Electronic Resource

Gastrointestinal Transit of a Solid Indigestible Capsule as Measured by Radiotelemetry and Dual Gamma Scintigraphy (1989)

Mojaverian, Parviz ; Chan, Keith ; Desai, Anil ; [et al.]

Springer

Pharmaceutical research 6 (1989), S. 719-724

add to mindlist on the mindlist

Details

ISSN: 1573-904X

Keywords: gastric residence time ; radiotelemetry ; small bowel transit time ; dual gamma scintigraphy ; Heidelberg capsule ; intragastric pH ; ileocecal junction ; indigestible solid

Source: Springer Online Journal Archives 1860-2000

Topics: Chemistry and Pharmacology

Notes: Abstract The objectives of the present study were to evaluate gastric and small bowel transit times of an indigestible solid matrix and to characterize the specific changes in intraluminal pH as a function of transit time through the gastrointestinal tract. Particular attention was paid to the lag time at the ileocecal junction. A Heidelberg capsule (HC), labeled with 10 µCi Indium-111, was given orally to six healthy male subjects 15 min after oral ingestion of 100 µCi of 99mTc-sulfur colloid as a liquid fatty meal (4 ml/kg). Intraluminal pH was monitored continuously via the HC. Gastric and small bowel transit of the radionuclides was monitored via external scintigraphy at 0.5-hr intervals. Gastric residence times (GRT) of the HC ranged from 2.8 to 4.8 hr, with a mean (±SD) of 3.6 ± 0.8 hr. These values were independent of the individual's weight, height, or body surface area. Small bowel transit times of the HC ranged from 2.8 to 〉5.5 hr, which were consistent with the reported values of 3 to 5 hr. The lag times of the HC at ileocecal junction ranged from 0.8 to 〉2.5 hr. The presence of the lag times at the ileocecal junction in all subjects confirmed that it acts as a valve or sphincter. Mouth-to-cecum transit times of the HC occurred within 9.0 hr in 50% of the subjects. In general, following a sharp rise upon pyloric passage of HC the pH dropped slightly but then increased linearly throughout the small intestine. The mean duodenal pH was 5.8 ± 0.8 and the pH at the ileocecal junction ranged from 6.5 to 8.5, with a mean of 7.3 ± 0.7. Passage through the ileocecal junction was associated with a 0.5- to 1.0-unit rise in pH in three subjects who exhibited passage of the HC into the large bowel within the study period. The present data may have implications in the designing of more effective dosage forms with specific delivery to proximal or distal small bowel regions.

Type of Medium: Electronic Resource

URL: http://dx.doi.org/10.1023/A:1015998708560

Permalink