Biomedical subjects

P W Lücker

Publications and source records attributed to P W Lücker.

At least 19 recordsLinked to original sources

PubMed2003

Relative bioavailability and bioequivalence of a newly developed fixed combination sachet of acetylsalicylic acid and pseudoephedrine compared with a preliminary combination.

Acetylsalicylic acid (ASA) and pseudoephedrine (PSE) are often administered together for the treatment of symptoms of the common cold, i.e., nasal congestion, runny nose, sore throat and headache. Based on this fact we developed a fixed combination of 500 mg ASA and 30 mg PSE, the recommended doses for both drugs for treating symptoms of the common cold, as granulate to be dissolved in water for administration. The purpose of this open, randomized, three-factorial (three-treatment, three-period, six-sequence) Latin Square clinical study was to investigate the relative bioavailability of ASA and PSE as well as the establishment of bioequivalence after single administration of the fixed combination (final formulation for approval) of 500 mg ASA/30 mg PSE*HCl and the preliminary formulation of this combination. Pharmacokinetic characteristics AUC(norm) and C(max,norm) of ASA, its metabolite SA, and PSE, were determined as measure of rate and extent of absorption of the two formulations. The treatment ratios final/preliminary formulation and their corresponding 90% confidence intervals were calculated to establish bioequivalence. Additionally, descriptive statistics were calculated for the parameters t(max), t((1/2)), and mean residence time (MRT). In total, data from 18 healthy male volunteers were included in the pharmacokinetic evaluation. The primary target parameters were analyzed using an analysis of variance (ANOVA) after logarithmic transformation of the data. Confidence intervals of 90% were calculated for the geometric means of ratios using the mean square error term of the ANOVA. Bioequivalence criteria were fulfilled for AUC(norm) and C(max,norm). Geometric means of individual ratios of AUC(norm) and of C(max,norm) showed equal bioavailability of the new formulation compared with the preliminary. Furthermore, a relative bioavailability of approximately 100% of the preliminary formulation was shown for the newly developed formulation for all parameters. The parameters t(max), t((1/2)), and MRT showed comparable results for ASA, SA, and PSE, respectively, in both formulations. The supplementary evaluation for the non-normalized original parameters AUC and C(max) also revealed bioequivalence. For the newly developed formulation, the arithmetic means of the parameters AUC and C(max) for PSE were 1040.66 mg/h*l and 134.52 mg/l, for SA 142.28 mg/h*l and 30.34 mg/l, respectively. The median t(max) values were 0.67 h for PSE and 0.92 h for SA. Both treatments were safe and well tolerated.

Administration, Oral↗

PubMed1999

Effect of processed and non-processed coffee samples on gastric potential difference. Study with healthy male Helicobacter pylori-positive and Helicobacter pylori-negative volunteers.

In an open trial with 18 healthy male volunteers (21-45 years old) the effect of processed (test) and non-processed (reference) coffee samples of same origin on the gastric potential difference (GPD) was studied. Test coffee samples were processed with the patented "Darboven improvement procedure" before roasting. All treatment groups were subdivided according to the Helicobacter pylori status of the volunteers. The evaluation of the target parameters Reizindex (RI), area under the baseline (AUB), maximum potential difference (Pdmax) and total time (ttot) revealed a significant lower RI (p = 0.0282) and AUB (p = 0.0136), and a significant shorter ttot (p = 0.0286) for the processed coffee. Total cholesterol, high-density lipoprotein (HDL) cholesterol, and pancreatic peptides showed a comparable marked increase of the arithmetic mean with both coffee samples, however, being more intense in the Helicobacter pylori-positive subgroup than in the Helicobacter pylori-negative subgroup. No negative findings concerning tolerability and safety could be seen. In conclusion, the test coffee samples processed with a new method to improve the stomach mucosal irritation-potential of coffee charges revealed a remarkably lower stomach mucosal irritation.

Adult↗

PubMed1998

Pharmacokinetics of acetazolamide in healthy volunteers after short- and long-term exposure to high altitude.

Exposure to high altitude results in significant physiologic changes and may precipitate mountain sickness, ranging from mild symptoms above 2,500 m to severe symptoms above 4,000 m. In a previous study, changes in the pharmacokinetics of meperidine were observed after exposure to high altitude. This study was conducted to investigate whether similar changes occur for acetazolamide, which is prescribed for prophylaxis of acute mountain sickness. Acetazolamide 250 mg was administered orally to young, healthy male volunteers in groups of 12 each: those residing at sea level (group L), these same volunteers on the day after arrival at high altitude (4,360 m, group HA), and volunteers living at high altitude for 10 months or longer (group HC). Serial blood samples were collected for 24 hours and acetazolamide concentrations were measured in whole blood, plasma, and plasma water. The elimination rate constant (lambda z) was significantly increased in group HA compared with group L. Clearance uncorrected for bioavailability (Cl/F) increased significantly in group HA compared with group L, and further increased in group HC. Apparent volume of distribution (Vz/F) was decreased by 17% in group HA compared with group L, and increased by 37% in group HC compared with group HA. Mean residence time (MRT) was significantly decreased in group HA compared with groups L and HC. Erythrocyte (RBC) uptake increased significantly after a significant increase in RBC count in group HC compared with group L. The extent of protein binding (EPB), however, was significantly decreased in group HA compared with groups L and HC. Free acetazolamide concentrations were significantly lower in group HC than in group L 12 hours after administration. Based on these observations, it is suggested that patients travelling to high altitude, especially altitudes above 4,000 m, should be closely monitored and acetazolamide dosage adjusted as necessary.

Acetazolamide↗

PubMed1998

Equipotent inhibition of gastric acid secretion by equal doses of oral or intravenous pantoprazole.

BACKGROUND: Pantoprazole is a proton pump inhibitor characterized by a low potential to interact with the cytochrome P450 system, and linear pharmacokinetics. The recommended oral dose for treatment of acid-related diseases is 40 mg. METHODS: Using a randomized, crossover study design we compared the ability of 40 mg oral and intravenous pantoprazole to elevate the intragastric pH in healthy volunteers (n = 20, 'per protocol'), during two treatment phases. The duration of each phase was 5 days. Pantoprazole 40 mg was administered once daily either as a tablet or as an intravenous injection. A 24 h pHmetry was used to record the intragastric pH on day 5 of each regimen; this was compared to the baseline curve obtained before each study period. The calculated 90% confidence intervals (90% CI) represent the mean difference in the intragastric pH, attained after intravenous or oral administration. The predefined equivalence range for the 90% CI was +/- 20% for the percentage time at which the gastric pH was at least pH 3 or 4 and +/- 1 unit for the median pH. RESULTS: Pantoprazole was well tolerated during both treatment phases. The mean of the 24 h median pH was 3.3 and 3.1 for the intravenous and oral treatments, respectively; the corresponding differences were 0.2 (90% CI: - 0.03 to 0.44). For the mean percentage time at which the pH was 3 or above, the respective calculated values were 57% and 51%, with a difference between the two administration routes of only 5.7% (90% CI: 1.8 to 9.6). At an intragastric pH of 4 or above, the mean percentage time was 420% and 38% following intravenous and oral treatment, respectively, with a difference between the treatment routes of only 4.4% (90% CI: 0.6 to 8.3). CONCLUSIONS: These results imply that the two formulations of pantoprazole can be assumed to be equipotent. Hence, the intravenous formulation of pantoprazole could be considered as an alternative route of administration.

2-Pyridinylmethylsulfinylbenzimidazoles↗

PubMed1998

Urinary excretion of acetazolamide in healthy volunteers after short- and long-term exposure to high altitude.

Acetazolamide is recommended for the prophylaxis of acute mountain sickness symptoms which sets in on climbing to high altitudes (H) above 2,500 m. It is primarily excreted unchanged in urine. In a previous study, we reported on the changes in urinary excretion of meperidine and its metabolite normeperidine on exposure to high altitude. In this study, we investigated the effect on urinary excretion of acetazolamide. The study was carried out in three groups of 12 healthy male volunteers each: at sea level (group L), these same volunteers the day after arrival at high altitude of 4,360 m (group HA), and subjects residing for approximately 10 months at high altitude (group HC). Urine was collected for the periods of 0-2, 2-4, 4-8, 8-12, 12-24 and 24-36 h after peroral administration of a single 250 mg dose. Urinary pH was measured and the concentrations of acetazolamide were determined. There were no significant changes observed in the amount of acetazolamide excreted in urine over 36 h. The urinary pH ranged from 4.5 to 7.8 for L, from 4.2 to 6.9 for HA and from 3.1 to 6.7 for HC. The Fel (fraction eliminated unchanged in urine) was calculated from the amount excreted in 36 h in urine and dose, assuming a bioavailability of 1 based on literature data. No significant changes in Fel were seen.

Acetazolamide↗

PubMed1998

Effect of differently processed coffee on the gastric potential difference and intragastric pH in healthy volunteers.

The gastric irritation potential of orally administered coffee (150 ml) was investigated in four healthy volunteers by continuous measurement of gastric potential difference (GPD) and intragastric pH. Furthermore, serum gastrin concentrations were measured up to 45 min after administration of the coffee. One of the coffees, untreated, had to be compared with a pretreated coffee. The evaluation of the target parameters Reiz-Index, AUB, Pdmax and ttot revealed a significant difference between untreated coffee and specially treated coffee: the improved coffee processing produced significantly less mucosal irritation. Regarding the intragastric pH, no significant differences between the treatments were observed and no stimulation of gastric acid secretion following coffee was measurable. No consistent effect on serum gastrin concentration was seen: two of the four subjects had a steep increase in serum gastrin following administration with a clear difference between the differently processed coffees, whereas the other two subjects showed no change in serum gastrin. The results of this pilot study confirm the findings of former experiments on the reliability of continuous transmural GPD measurement when investigating the mucosal irritation potential of barrier breakers.

Coffee↗

PubMed1997

Optimizing the absorption of valspodar, a P-glycoprotein modulator, Part I: Selecting an oral formulation and exploring its clinical pharmacokinetics/dynamics.

Valspodar is a cyclosporine D analog used as a chemotherapy adjunct for modifying multidrug resistance. Two studies were sequentially performed to select an optimal oral formulation and to characterize selected aspects of its clinical pharmacokinetics/dynamics. An initial four-way crossover study with 20 volunteers compared the pharmacokinetics of single fasting administrations of 200 mg by intravenous infusion and 600 mg orally as a conventional oral solution, a microemulsion oral solution, and a microemulsion soft gelatin capsule. The two microemulsion dosage forms demonstrated significantly faster and less variable rates of absorption compared with the conventional oral solution. The microemulsion dosage forms were bioequivalent with absolute bioavailability nearly double that of the conventional oral solution. Based on these results, the microemulsion capsule was further investigated in a four-way randomized crossover study with 24 volunteers who received single fasting administrations of 200, 400, and 600 mg and a 400-mg administration after a fat-rich meal. Dose proportionality in area under the curve (AUC) was demonstrated over this dose range. Administration after a fat-rich meal caused a slight time lag until absorption began, a delay in time to reach the peak concentration, and a moderate increase of 24% in AUC. Serial determinations of total bilirubin were explored as a potential pharmacodynamic marker for P-glycoprotein inhibition. A similar magnitude of reversible hyperbilirubinemia was seen at all dose levels suggesting that P-glycoprotein inhibition in the biliary canaliculi was maximal even at the lowest dose tested. The microemulsion formulation (oral solution or soft gelatin capsule) represents an improved and less variable oral delivery form providing dose-proportional drug exposure over a clinically relevant dose range.

ATP Binding Cassette Transporter, Subfamily B, Mem↗

PubMed1997

Concomitant administration of the alpha-glucosidase inhibitor voglibose (AO-128) does not alter the pharmacokinetics of glibenclamide.

OBJECTIVE: Voglibose is a new and potent inhibitor of alpha-glucosidases used for treatment of diabetes mellitus. It increases gastro-intestinal motility and could thus affect absorption of other concurrently administered antidiabetic drugs. The aim of this study was to investigate whether or not voglibose modifies the pharmacokinetics of glibenclamide, a widely used oral antidiabetic, and the glibenclamide-induced decrease in fasting serum glucose. METHODS: Twelve healthy male subjects were included in this double-blind cross-over study and received a single 1.75-mg dose of glibenclamide on the 8th day of continuous administration of either placebo (reference) or voglibose 5 mg t.i.d. (test). Blood samples were taken to determine the pharmacokinetic characteristics of glibenclamide and the test/reference ratios were evaluated according to bioequivalence criteria. Additional blood samples were taken to measure serum glucose on the same day. RESULTS: The concentration-time course of glibenclamide under concomitant voglibose administration was similar to that under placebo. The equivalence ratio (test/reference) for the pharmacokinetic characteristics AUCnorm was 1.03 (geometric mean; 0.95-1.11, 90% confidence interval) and Cmax.norm 1.01 (0.94-1.08). The parameters were within the accepted range of 0.8-1.25 (AUC) or 0.7-1.43 (Cmax), thus fulfilling equivalence criteria and indicating no effect of voglibose on glibenclamide kinetics. The glibenclamide-induced decrease in fasting serum glucose concentration was similarly independent of placebo or voglibose co-administration. CONCLUSIONS: Voglibose did not interact with glibenclamide on a pharmacokinetic level. Concomitant treatment was well tolerated and has been proven to be safe for further clinical use.

Adult↗

PubMed1997

The alpha-glucosidase inhibitor voglibose (AO-128) does not change pharmacodynamics or pharmacokinetics of warfarin.

OBJECTIVE: Voglibose is a new and potent inhibitor of alpha-glucosidases and is used for the treatment of diabetes mellitus. Since voglibose increases gastrointestinal motility and could thus affect absorption of concomitantly administered drugs, it was investigated whether or not voglibose modifies the pharmacodynamics and pharmacokinetics of warfarin, an oral anticoagulant frequently used in cardiovascular disorders likely to arise in diabetic patients. METHODS: Twelve healthy male subjects were given individually adjusted doses of warfarin to reduce prothrombin time (Quick's method) to a value of about 30-40% of the normal range within the first 8 days. Then, the individuals maintenance dose, given in the morning, was maintained until day 15. On study days 11-15, voglibose was co-administered per os in a dose of 5 mg t.i.d. The prothrombin time was determined on days 10 and 11 (reference) and on days 15 and 16 (test), and the steady-state pharmacokinetic characteristics of the warfarin enantiomers were determined on days 10 (reference) and 15 (test). The ratios test/reference were evaluated according to bioequivalence criteria. RESULTS: The equivalence ratio (test reference) for the pharmacodynamic parameter prothrombin time was 0.97 and for the pharmacokinetic characteristics AUC0-24 h.t.ss: S-(-)-warfarin, 1.05; R-(+)-warfarin, 1.01; and Cmax.ss: S-(-)-warfarin, 1.08; R-(+)-warfarin, 1.04. All parameters were within the predetermined accepted range of 0.7-1.43 (pharmacodynamics) or 0.8-1.25 (pharmacokinetics), thus fulfilling equivalence criteria. CONCLUSIONS: Voglibose modified neither the pharmacodynamics nor the pharmacokinetics of warfarin under steady-state conditions. Concomitant treatment was well tolerated and has been proven to be safe for further clinical use.

Adult↗

PubMed1997

Effect of buffering on pharmacokinetics of ketoprofen enantiomers in man.

AIMS: Concomitant administration of magnesium hydroxide may affect the rate or extent of absorption of non-steroidal anti-inflammatory drugs. In order to find out whether or not buffering modifies the pharmacokinetics of ketoprofen, plasma concentration-time courses resulting from oral administration of unbuffered formulations were compared with those of buffered formulations. METHODS: Two groups of 12 healthy and young male subjects were included in two randomized cross-over studies and received single oral doses of ketoprofen 12.5 or 25 mg, respectively, given as tablets which were either unbuffered or buffered with magnesium hydroxide/citrate. Ketoprofen enantiomers in plasma were determined by h.p. l.c. up to 24 h post-dose. RESULTS: Maximum plasma concentrations (Cmax) of both the (R)- and (S)-enantiomer, observed after administration of the buffered formulations (12.5 and 25 mg), were higher compared with the unbuffered tablets by about 50-80%. The area under concentration-time data (AUC) was unaffected, and, hence, Cmax/AUC was increased by buffering. Time to Cmax (tmax) and mean residence time (MRT) tended to be or was shortened by buffering. CONCLUSIONS: It is concluded that buffering of two ketoprofen formulations with magnesium hydroxide/citrate enhanced the concentration maximum by increasing the rate of absorption and leaving AUC unaffected.

Adult↗

PubMed1997

Influence of cholestyramine on the pharmacokinetics of cerivastatin.

The possible influence of the bile acid sequestering agent cholestyramine, a basic comedication in hypercholesterolemic patients, on the pharmacokinetics of the new HMG-CoA reductase inhibitor cerivastatin was investigated. When both drugs were administered concomitantly in the morning under fasting conditions, a decrease in relative bioavailability by 21% could be observed, possibly due to irreversible adsorption of the statin to the resin. In addition, the delay in absorption led to a 41% decrease in cerivastatin mean maximum plasma concentration which also occurred at later time. A second study addressed in detail the question of time interval required between both treatments to minimize the influence of cholestyramine pretreatment on cerivastatin bioavailability: dosing of cerivastatin at dinner (6 p.m.) or bed time (10 p.m.) with cholestyramine pretreatment 1 hour before meal (5 p.m.) in both treatments. The decrease in mean AUC was now approximately 8-16% depending on the time of pretreatment (1-hour-interval: 16%, 5-hour-interval: 8%), and Cmax decreased by approximately 32%, irrespective of the time of pretreatment. Tmax was increased in both treatments, whereas t1/2 was not changed. The presented data support the conclusion that when administered concomitantly, the bioavailability of cerivastatin is moderately reduced by adsorption to cholestyramine. Following, however, the dosing instructions of both cholestyramine (1 hour before meal) and cerivastatin (once-daily in the evening at dinner or at bed time), i.e. administering both drugs several hours (at least 1 hour) apart, the observed effects on rate and extent of absorption of cerivastatin are unlikely to be of clinical relevance.

Absorption↗

PubMed1996

Pharmacokinetics of meperidine in healthy volunteers after short- and long-term exposure to high altitude.

Increased numbers of erythrocytes have been shown ex vivo to increase meperidine uptake, and one of the major physiologic changes that occurs at high altitude is an increase in hematocrit and erythrocytes. A study was therefore conducted to evaluate the effects of high altitude on the pharmacokinetics of meperidine. Intramuscular doses (0.75 mg/kg) of meperidine were given to three groups of healthy volunteers (age range, 18-20 years): participants living at sea level (group L), those same participants the day after arrival at high altitude (4,360 m; group HA), and participants who had lived at high altitude for > or = 10 months (group HC). Blood samples were collected for 12 hours after drug administration. Meperidine was measured in whole blood, plasma, and plasma water. Elimination rate constant (lambda z) and clearance uncorrected for bioavailability (Cl/F) were significantly lower at high altitudes than at sea level in plasma (HA and HC) and in whole blood (HA only). Mean residence time (MRT) was significantly higher at high altitudes than at sea level in plasma (HA and HC) and in whole blood (HA only). Hematocrit was significantly increased at both time points at high altitude in comparison to values at sea level, and was also higher after a long-term stay at high altitude than after arrival at high altitude. Erythrocyte binding increased significantly from 41.3% at sea level to 43.8% at arrival at high altitude to 50.9% after a long-term stay at high altitude. The extent of protein binding tended to decrease with high altitude, but this decrease was not significant. Free concentrations of meperidine in plasma water measured 1, 2, and 4 hours after administration were significantly increased after 2 and 4 hours.

Adolescent↗

PubMed1996

Lack of pharmacodynamic and pharmacokinetic interaction between pantoprazole and phenprocoumon in man.

OBJECTIVE: Pantoprazole is a selective proton pump inhibitor characterized by a low potential to interact with the cytochrome P450 enzymes in man. Due to the clinical importance of an interaction with anticoagulants, this study was carried out to investigate the possible influence of pantoprazole on the pharmacodynamics and pharmacokinetics of phenprocoumon. METHODS: Sixteen healthy male subjects were given individually adjusted doses of phenprocoumon to reduce prothrombin time ratio (Quick method) to about 30-40% of normal within the first 5-9 days and to maintain this level. The individual maintenance doses remained unaltered from day 9 on and were administered until day 15. Additionally, on study days 11-15, pantoprazole 40 mg was given per once daily. As a pharmacodynamic parameter, the prothrombin time ratio was determined on days 9 and 10 (reference value) and on days 14 and 15 (test value), and the ratio test/reference was evaluated according to equivalence criteria. RESULTS: The equivalence ratio (test/reference) for prothrombin time ratio was 1.02 (90% confidence interval 0.95-1.09), thus fulfilling predetermined bioequivalence criteria (0.70-1.43). The pharmacokinetic characteristics AUC0-24h and Cmax of S(-)- and R(+)-phenprocoumon were also investigated using equivalence criteria. Equivalence ratios and confidence limits of AUC0-24h and of Cmax of S(-)-phenprocoumon (0.93, 0.87-1.00 for AUC0-24h; 0.95, 0.88-1.03 for Cmax) and of R(+)-phenprocoumon (0.89, 0.82-0.96; 0.9, 0.83-0.98) were within the accepted range of 0.8-1.25. CONCLUSION: Pantoprazole does not interact with the anticoagulant phenprocoumon on a pharmacodynamic or pharmacokinetic level. Concomitant treatment was well tolerated.

2-Pyridinylmethylsulfinylbenzimidazoles↗

PubMed1996

Twenty-four-hour intragastric pH profiles and pharmacokinetics following single and repeated oral administration of the proton pump inhibitor pantoprazole in comparison to omeprazole.

BACKGROUND: Pantoprazole is a proton pump inhibitor characterized by a low potential to interact with the cytochrome P450 enzyme system in man. Its effect on intragastric pH following single and repeated oral intake was investigated in comparison to omeprazole by continuous intragastric pH-metry at doses recommended for treatment of peptic ulcer disease. METHODS: Sixteen healthy male subjects underwent two dosing periods. From day 1 to day 7, they were given once daily by mouth 40 mg pantoprazole in one period and 20 mg omeprazole in the other period, according to a double-blind randomized crossover design. Twenty-four-hour intragastric pH was recorded and frequent blood samples for pharmacokinetic analysis were taken on day 1 and day 7. A placebo pH profile was obtained prior to each treatment period. RESULTS: Pantoprazole was significantly more effective than omeprazole with regard to increase in 24-h and daytime pH, following both single (median 24-h pH: 1.45 vs. 1.3, P < 0.05; median daytime pH: 1.6 vs. 1.3, P < 0.01) and repeated (median 24-h pH: 3.15 vs. 2.05, P < 0.01; median daytime pH: 3.8 vs. 2.65, P < 0.05) oral intake. As compared to the first dose, repeated administration of both drugs markedly increased the effect on intragastric pH. With pantoprazole, steady-state serum concentrations were obtained after the first dose, but not with omeprazole. Both drugs were well tolerated without relevant changes in vital signs of clinical laboratory parameters. CONCLUSION: Pantoprazole 40 mg is significantly more effective than omeprazole 20 mg in raising intragastric pH.

2-Pyridinylmethylsulfinylbenzimidazoles↗

PubMed1996

Comparative clinical efficacy and tolerability of oxerutins and horse chestnut extract in patients with chronic venous insufficiency.

Oxerutins (O-(beta-hydroxyethyl)rutosides, HR, Venoruton) and horse chestnut extract (HCE) are active principles of first priority for the pharmacological treatment of chronic venous insufficiency (CVI). The efficacies of both compounds were shown in numerous, double-blind, randomized, placebo controlled clinical trials. Besides the direct comparison of the two compounds the aim of the study was to investigate the initial dose/maintenance dose concept for HR. 137 female, postmenopausal patients with CVI II finished the study according to protocol. Following one week placebo run-in the patients were treated either with 1000 mg/d HR, 600 mg/d HCE or 1000 mg/d for 4 weeks and than with 500 mg/d HR within the initial dose/maintainance dose concept for 12 weeks and observed for further 6 weeks. A main confirmative criterion was the volume reduction of the leg. Subjective criteria were descriptively evaluated. HR (1000 mg/d) was proven to be equivalent or better, reducing the leg volume (AUB0-18) by -5273 +/- 11418 ml.d compared to -3187 +/- 10842 ml.d under HR (1000 mg/d and 500 mg/d), and -3004 +/- 7429 ml.d under HCE-treatment. Both compounds exhibit a substantial carry-over effect. The maintenance posology of HR is able to stabilize the therapeutic obtained under initial dose conditions.

Aged↗

PubMed1995

Voglibose (AO-128) is an efficient alpha-glucosidase inhibitor and mobilizes the endogenous GLP-1 reserve.

The alpha-glucosidase inhibitor voglibose (AO-128) was designed to prevent rapid postprandial blood glucose rises in non-insulin-dependent diabetics. We analyzed its effect on the entero-insular axis in 72 healthy volunteers in a double-blind study design before, after the 1st dose, and on the 7th day of a 7-day treatment protocol (3 daily loads). Six parallel groups of 12 volunteers received voglibose (0.5, 1.0, 2.0, or 5.0 mg) or placebo (two groups). Blood was drawn at regular intervals up to 180 min after a standardized breakfast to analyze the levels of glucose, insulin, C peptide, gastric inhibitory polypeptide, and glucagon-like peptide 1 (GLP-1). As expected, after ingestion of voglibose, slight to moderate gastro-intestinal discomfort but no severe side-effects were reported. In a dose-dependent manner, voglibose significantly reduced postprandial increases of blood glucose, insulin, and C peptide. At the lower loads (0.5 and 1 mg voglibose three times daily), these effects were more pronounced after 7 days. The postprandial increase of gastric inhibitory polypeptide was already reduced after the first load of 2 and 5 mg voglibose. In comparison to the placebo group, this inhibition became also significant for the lower loads after 7 days. Interestingly, GLP-1, originating from the lower intestines, was increasingly released under voglibose treatment. The first administration of 1 mg voglibose enhanced GLP-1 secretion > 80% above controls. Treatment with 1 mg voglibose three times daily over 7 days revealed a maximal mobilizing effect on endogenous GLP-1 (> 90% above controls) which was not further increased by 2- or 5-mg loads. We conclude that voglibose treatment effectively inhibits intestinal disaccharidases and thereby mobilizes the endogenous pool of insulinotropic GLP-1.

Adolescent↗

PubMed1995

Pharmacokinetics and relative bioavailability after single dose administration of 25 mg ketoprofen solution as compared to tablets.

The relative bioavailability of ketoprofen from a liquid formulation as compared to a tablet formulation as reference after single oral dose administration was investigated in 16 healthy male subjects. The subjects received in a randomized, crossover design during one study period of 5 days 2.5 mg of ketoprofen as tablet or liquid formulation administered as single dose with a washout interval of 48 h. The plasma concentrations of S(+)- and R(-)-ketoprofen were determined before and up to 24 h post-administration. S(+)- and R(-)-ketoprofen in the collected plasma samples was determined using an internally standardized validated HPLC method. Regarding the geometric mean concentration-time courses there were no relevant differences between the two ketoprofen enantiomers for both formulations. Remarkable differences in the shape of concentration-time courses between the two formulations were found with higher Cmax (by about 70%) and earlier tmax (by 15 min) values for the ketoprofen solution. The treatments were widely equivalent with regard to AUC. The quotients of geometric means as well as 90% confidence intervals for AUC of R(-)-ketoprofen were 95.72% (92.55-99.00%) and for S(+)-ketoprofen 94.23% (89.91-98.76%). The administration of the ketoprofen solution resulted earlier in higher concentrations (by about 70%) for both enantiomers, whereas the extent of absorption expressed by AUC was nearly the same (about 95%) as compared to the equimolar tablet formulation. The differences between the two formulations for Cmax,norm and tmax were statistically significant.

Adolescent↗

PubMed1995

Relative bioavailability of DL-oxyfedrine HCl after single-dose oral administration of tablets as compared to equimolar solutions.

The pharmacokinetics and comparative bioavailability of oxyfedrine after single-dose oral administration of oxyfedrine*HCl tablets in comparison to an equimolar aqueous solution of oxyfedrine*HCl were investigated in 12 healthy male subjects. Six of them received 96 mg DL-oxyfedrine*HCl as tablets and solution and the remaining 6 subjects received 16 mg DL-oxyfedrine*HCl as tablets and solution in a randomized cross-over design. For evaluation of the relative bioavailability of the tablet formulation, the main metabolite norephedrine (expressed as hydrochloride) was analyzed in plasma for all 12 subjects. Furthermore, for determination of the parent drug, samples of whole blood were analyzed for DL-oxyfedrine*HCl. Relevant concentrations of the parent drug were found only in the high dosage group. There was no evidence of dose-linearity referring to AUC and Cmax of norephedrine between 16-mg and 96-mg doses of DL-oxyfedrine*HCl. The relative bioavailability of the tablet formulation after administration of 16 mg DL-oxyfedrine*HCl, based on the metabolite norephedrine*HCl was for AUC: 85.37% within a 90% confidence interval of 69.29-105.17% and for Cmax: 78.79% within a 90% confidence interval of 59.19-104.90%. The figures for the 96 mg dose strength were: AUC: 107.85% (90.06-129.15%) and for Cmax: 74.74% (62.48-89.42%).

Administration, Oral↗