Biomedical subjects

H Mascher

Publications and source records attributed to H Mascher.

At least 19 recordsLinked to original sources

PubMed2004

Clonidine added to bupivacaine enhances and prolongs analgesia after brachial plexus block via a local mechanism in healthy volunteers.

BACKGROUND AND OBJECTIVE: The addition of clonidine to local anaesthetics enhances pain relief after peripheral nerve block, but the site of action is unproven. METHODS: Seven healthy volunteers underwent three brachial block procedures using bupivacaine 0.25% 1 mg kg(-1) + epinephrine 1:200,000 (=local analgesic) in a randomized, double-blind cross-over fashion: (a) control treatment: local analgesic with 0.9% sodium chloride solution for the block and an intramuscular injection of saline; (b) intramuscular treatment: local analgesic with 0.9% NaCl for block and an intramuscular injection of clonidine 2 microg kg(-1) and (c) block treatment: local analgesic with clonidine 2 microg kg(-1) for block and an intramuscular injection of saline. RESULTS: The onset and duration of complete blockade (sensory/motor/temperature) was evaluated in the four nerve regions of the hand and forearm. Additionally, sedation score, blood pressure, heart rate and plasma clonidine concentrations were determined. The median duration of complete sensory blockade was 270 min (range 0-600) for block treatment compared to 0 min (range 0-480) for intramuscular treatment (P < 0.05) and 0 min (range 0-180) for control treatment (P < 0.05). Motor and temperature blockade exhibited similar results. Administration of clonidine was associated with sedation and a decrease in heart rate and blood pressure independent of the route of administration. Plasma clonidine concentrations were lower for block compared to the intramuscular treatment. CONCLUSIONS: The admixture of clonidine to bupivacaine plus epinephrine prolongs and enhances brachial plexus blockade. Lower clonidine plasma concentrations for block treatment strongly suggest a local effect.

Adult↗

PubMed2004

Topical skin penetration of diclofenac after single- and multiple-dose application.

OBJECTIVE: Transdermal penetration of nonsteroidal anti-inflammatory drugs (NSAIDs) has been shown to be highly variable. The present study was performed to gain insight into the transdermal penetration process of topically applied diclofenac and to test whether transdermal absorption leads to pharmacologically effective concentrations in dermal tissue layers beneath the application site. MATERIAL AND METHOD: Six healthy male volunteers participated in this 2-way crossover study and were assigned to 2 treatment groups. In the first group, diclofenac was applied at a therapeutic dose of 60 mg/100 cm2 3 times daily for 4 days with subsequent occlusion with a plastic foil for 4 hours to enhance transdermal drug absorption. After a 1-week wash-out, diclofenac was applied at a single dose of 300 mg/100 cm2 without occlusion. Diclofenac in both groups was applied on a previously shaven area of the thigh. Transdermal penetration was assessed employing in vivo microdialysis. RESULTS: After multiple-dose administration mean diclofenac concentrations of 0.48 +/- 0.35 ng x ml(-1) were observed in subcutaneous tissue (mean +/- SEM). The mean AUC(subcutis/plasma) ratio of 0.08 +/- 0.02 indicates redistribution of diclofenac from the systemic circulation to the tissue. After single-dose treatment, mean tissue concentrations were 24.26 +/- 46.43 ng x ml(-1) with a mean AUC(subcutis/plasma) ratio of 60.85 +/- 57.59, which suggests direct tissue penetration of diclofenac. CONCLUSIONS: Transdermal penetration of diclofenac after multiple as well as after single application of the present formulation is highly variable. In addition to other factors influencing the transdermal penetration process, dose and mode of administration are important factors determining whether pharmacologically effective local tissue concentrations are attained.

Administration, Cutaneous↗

PubMed2002

[Pharmacokinetics of carvone and menthol after administration of peppermint oil and caraway oil containing enteric formulation].

Enteric coating of peppermint oil/caraway oil capsules avoids subjective discomfort to the patient caused by gastroesophgeal reflux. In order to confirm bioequivalence of an enteric coated formulation containing peppermint oil and caraway oil (Enteroplant) and an immediate release formulation of both oils, the pharmacokinetics of menthol and carvone after oral administration of the two formulations were studied in a randomized, two-period crossover study in 16 healthy male volunteers. The subjects received 180 mg peppermint oil and 100 mg caraway oil, once as 2 enteric coated capsules of the fixed combination preparation Enteroplant containing 90 mg peppermint oil and 50 mg caraway oil each (test) and once in the form of 5 capsules of an immediate release formulation (reference) containing 36 mg peppermint oil and 20 mg caraway oil each. The capsules were taken with 250 ml water after a 10 h fast. Both substances were determined in plasma by GC/MS after extraction. The limit of quantification was 10 ng/ml for menthol and 0.5 ng/ml for carvone. The mean maximum plasma levels for menthol were 1196 ng/ml after administration of the test medication and 1492 ng/ml after administration of the reference medication. The bioavailability with respect to the AUC was comparable after administration of test and reference preparation, the 90% confidence interval was 97 to 105%. As expected, there were considerable differences for Tmax. After application of the enteric coated form the maximum concentration was reached significantly later (3.0 h vs. 1.7 h) compared to the immediate release capsule. Corresponding data were also calculated for carvone. After application of the test medication the maxima of 14 ng/ml for both formulations were reached later (2.5 h vs. 1.3 h). The 90% confidence interval of the AUC for carvone was 79% to 119% and therefore slightly outside the acceptable range for bioequivalence of 80% to 125%. However, this fact should not be relevant, in particular since the dosage of the enteric coated capsule lies at the upper limit of the model text and positive clinical studies, also on the therapeutic equivalence of the two formulations, are available.

Adult↗

PubMed2001

Pharmacokinetics of menthol and carvone after administration of an enteric coated formulation containing peppermint oil and caraway oil.

Enteric coating of peppermint oil/caraway oil capsules avoids subjective discomfort to the patient caused by gastroesophageal reflux. In order to confirm bioequivalence of an enteric coated formulation containing peppermint oil and caraway oil (CAS 277309-55-4, Enteroplant) and an immediate release formulation of both oils, the pharmacokinetics of menthol and carvone after oral administration of the two formulations were studied in a randomized, two-period cross-over study in 16 healthy male volunteers. The subjects received 180 mg peppermint oil and 100 mg caraway oil, once as 2 enteric coated capsules of the fixed enteric coated combination preparation containing 90 mg peppermint oil (WS 1340) and 50 mg caraway oil (WS 1520) each (test) and once in the form of 5 capsules of an immediate release formulation (reference) containing 36 mg peppermint (WS 1340) oil and 20 mg caraway oil (WS 1520) each. The capsules were taken with 250 ml water after a 10 h fast. Both substances were determined in plasma by GC/MS after extraction. The limit of quantification was 10 ng/ml for menthol and 0.5 ng/ml for carvone. The mean maximum plasma levels for menthol were 1196 ng/ml after administration of the test medication and 1492 ng/ml after administration of the reference medication. The bioavailability with respect to the AUC was comparable after administration of test and reference preparation, the 90% confidence interval was 97 to 105%. As expected, there were considerable differences for Tmax. After application of the enteric coated form the maximum concentration was reached significantly later (3.0 h vs. 1.7 h) compared to the immediate release capsule. Corresponding data were also calculated for carvone. After application of the test medication the maxima of 14 ng/ml for both formulations were reached later (2.5 h vs. 1.3 h). The 90% confidence interval of the AUC for carvone was 79 to 119% and therefore slightly outside the acceptable range for bioequivalence of 80 to 125%. However, this fact should not be relevant, in particular since the dosage of the enteric coated capsule lies at the upper limit of the model text and positive clinical studies, also on the therapeutic equivalence of the two formulations, are available.

Adult↗

PubMed2001

Bioequivalence between omeprazole MUPS 20 mg as tablet and omeprazole MUPS 20 mg as tablet encapsulated in a hard gelatine capsule.

AIMS: To investigate pharmacokinetic characteristics of omeprazole MUPS 20 mg tablets and its encapsulated form. MATERIAL AND METHODS: Bioequivalence of omeprazole MUPS 20 mg tablet (Reference) and omeprazole MUPS 20 mg tablet in a hard gelatine capsule (Test) was evaluated in a randomized, 2-period crossover study in 38 healthy male Caucasian subjects who received a single oral dose of 20 mg omeprazole in each study period. Serum concentrations of omeprazole MUPS 20 mg were measured using an HPLC assay. In addition, in vitro dissolution profiles were studied. RESULTS: Both formulations were bioequivalent as assessed by the primary pharmacokinetic characteristics AUC(0-infinity) and Cmax, the corresponding ratios (Test/Reference) being 0.97 and 0.98, respectively. Thus, the 90% CI of these ratios were within the equivalence range of 0.8 to 1.25 for AUC(0-infinity) (CI 0.90-1.04) and 0.67 to 1.50 for Cmax (Cl 0.86-1.10). The ratios of the secondary criteria, Cmax/AUC(0-infinity) and t 1/2, were also within the equivalence range. Median tmax of Reference and Test was identical. Both formulations revealed comparable dissolution profiles with high batch conformity and homogeneity releasing > 80% omeprazole within 1 hour. Both study formulations were well tolerated without relevant differences. CONCLUSION: The encapsulation of omeprazole MUPS 20 mg tablets does not influence the extent and rate of absorption as indicated by the AUC and Cmax ratios. Thus, bioequivalence could be demonstrated.

Adult↗

PubMed1999

Pantoprazole lacks induction of CYP1A2 activity in man.

OBJECTIVE: This drug-drug interaction study investigated the potential influence of the proton pump inhibitor pantoprazole on the CYP1A2 activity as assessed by urinary excretion of caffeine metabolites. SUBJECTS, MATERIALS AND METHODS: 12 healthy, non-smoking volunteers underwent two treatment periods of 7 days each in randomized order with once-daily oral intake of 40 mg pantoprazole (test) or placebo (reference). On days 6 and 7 of both periods, 200 mg caffeine was administered two hours after pantoprazole intake, i.e. at the expected t(max) of pantoprazole serum concentrations. Urinary excretion of the caffeine metabolites 1X, 1U, AFMU, 17U was measured up to 8 hours after caffeine intake. In accordance with recent guidelines on drug-drug interactions, lack of interaction was handled as an equivalence problem. RESULTS: Point estimate and 90% confidence intervals (CI) of the respective ratios test/reference were 0.91 (0.81, 1.03) for (1X + 1U + AFMU)/17U, indicative for CYP1A2 activity, 1.03 (0.94, 1.13) for AFMU/1X (N-acetyl transferase activity) and 1.01 (0.94, 1.09) for 1U/1X (xanthine oxidase activity). CONCLUSION: Pantoprazole does not induce CYP1A2 activity, consistent with previous findings following theophylline administration, nor does it have any influence on N-acetyl-transferase or xanthine oxidase activity.

2-Pyridinylmethylsulfinylbenzimidazoles↗

PubMed1998

Pharmacokinetics of dexibuprofen administered as 200 mg and 400 mg film-coated tablets in healthy volunteers.

The pharmacokinetic properties of 2 film-coated preparations containing 200 mg and 400 mg dexibuprofen were compared in a single-dose, crossover study in 16 healthy, male volunteers. Dexibuprofen was absorbed rapidly (tmax 2.1 - 2.2 hours) reaching maximum concentrations of 12.4 microg/ml (200 mg), respectively 12.0 microg/ml (400 mg dose adjusted). For the characteristics AUC(0-12h) and AUC(0-infinity) arithmetic means of 49.2 (microg) x (h/ml)(200 mg) and 48.2 (microg) x (h/ml)(400 mg dose-adjusted), respectively 50.5 (microg) x (h/ml)(200 mg), and 49.2 (microg) x (h/ml)(400 mg) were calculated. No relevant differences for the pharmacokinetic characteristics terminal half-life, clearance, volume of distribution, and mean residence time were observed. A linear dose-relationship was shown over the investigated dose range. Mean ratios after dosage adjustment of the test preparation using the "2 one-sided t-tests" procedure were calculated. Bioequivalence was assessed for AUC(0-12h) with a mean ratio of 97.7% (90% CI: 92.4 - 103.3%), for AUC(0-infinity) with 97.1% (90% CI: 91.4 - 103.1%), and for Cmax with 97.5% (90% CI: 91.7 - 103.8%). Both dexibuprofen preparations were well tolerated. No changes in hematological and biochemical parameters were detected.

Administration, Oral↗

PubMed1998

Pantoprazole does not interact with the pharmacokinetics of carbamazepine.

OBJECTIVE: Pantoprazole is a H+/K+-ATPase inhibitor with a minimized potential of interaction with the cytochrome P450 system. Imidazole derivatives such as cimetidine and omeprazole have been shown to markedly interact with carbamazepine, a major anticonvulsant with a narrow therapeutic range. Therefore, the influence of steady-state pantoprazole on the pharmacokinetics of carbamazepine was investigated. SUBJECTS AND METHODS: N = 20 healthy volunteers (12 male/8 female) completed a double-blind, placebo-controlled, randomized crossover study. During the test period they received 40 mg pantoprazole p.o. once daily for 11 days and concomitantly a single oral dose of 400 mg carbamazepine on day 5. In the reference period placebo was administered instead of pantoprazole. RESULTS: Serum concentrations of carbamazepine and its active metabolite carbamazepine-10,11-epoxide were measured until day 11. Geometric means of AUC (extent characteristic) and Cmax/AUC (rate characteristic) of carbamazepine were 292 and 287 mgxh/l, and 0.0150 and 0.0144 l/h (reference and test), respectively. Point estimates and 90% confidence intervals of the ratios were 0.98 (0.95, 1.01) for AUC, and 0.96 (0.92, 1.00) for Cmax/AUC, respectively. Since the 90% confidence intervals of the primary characteristics, AUC and Cmax/AUC were entirely within the predefined equivalence range of 0.80 - 1.25, lack of interaction of pantoprazole with the pharmacokinetics of carbamazepine was demonstrated. Equivalence was also demonstrated for carbamazepine-10,11-epoxide using the characteristics AUC and Cmax. CONCLUSION: No dose adjustment of carbamazepine is therefore required during concomitant treatment with pantoprazole.

2-Pyridinylmethylsulfinylbenzimidazoles↗

PubMed1997

Diclofenac concentrations in defined tissue layers after topical administration.

INTRODUCTION: To date it is unclear whether therapeutic concentrations are attained in target tissues after topical administration of nonsteroidal anti-inflammatory drugs. Therefore this study in healthy volunteers was undertaken to measure diclofenac concentrations attained in defined tissue layers directly underlying the site of topical diclofenac application by in vivo microdialysis. METHODS: In each experiment two microdialysis probes were inserted, one into a superficial (3.9 +/- 0.3 mm) and one into a deep (9.3 +/- 0.5 mm) tissue layer, in 20 healthy volunteers and calibrated in vivo. The distance between the surface of the skin and the tips of the microdialysis probes was measured by 7.5 MHz ultrasound. Diclofenac was administered topically as a single dose of approximately 300 mg/100 cm2. Concentration versus time profiles in tissue layers were monitored for 5 hours. RESULTS: Concentration versus time profiles were obtained in 11 of 20 experiments. However, there was no correlation between area under the concentration-time curve (AUC) in a defined layer and the depth of probe insertion. In those experiments where concentration versus time profiles were obtained for both probes mean AUC was 532 +/- 197 microg x min x ml(-1) for superficial layers, and 438 +/- 249 microg x min x ml(-1) for deep layers. CONCLUSION: We conclude that transdermal penetration of diclofenac, at least after single doses, is not predictable and may strongly be influenced by individual skin properties.

Administration, Cutaneous↗

PubMed1997

Preliminary toxicokinetic study with different crystal forms of S (+)-ibuprofen (dexibuprofen) and R,S-ibuprofen in rats.

The aim of the study was to gain information on the plasma concentration-time profiles of both ibuprofen (CAS 15687-27-1) enantiomers in the rat after single oral application of two different crystal forms of S (+)-ibuprofen (dexibrufen, CAS 51146-56-6) and racemic ibuprofen in order to optimize blood-sampling times in a subsequent subchronic toxicity study. The application of either commercial racemic ibuprofen or recrystallised S (+)-ibuprofen (60 mg/kg) to two groups of 4 rats per blood sampling term was carried out in order to define Cmax and tmax and AUC of the plasma-concentrations of the ibuprofen enantiomers. The crystals of commercial (manufactured according to an usual manufacturing procedure) and recrystallised (S(+)- and racemic ibuprofen were different in respect to their shape and size. The recrystallised crystal species of S (+)- and racemic ibuprofen has better galenic (tabletting-) properties and tablets containing the modified S (+)-ibuprofen species showed favorable clinical results. The toxicokinetic behaviour of the recrystallised species was investigated in comparison to the commercial crystal species because of its slightly but significantly slower dissolution rate in simulated gastric and enteric juice. As the AUC0-24 h S-(+)-ibuprofen and the AUC0-24 h, R-(-)-ibuprofen after application of commercial and recrystallised crystal species were not different, the crystal form apparently did not exert an influence on the extent of absorption of S-(+)-ibuprofen and racemic ibuprofen in the rat. The rat has a high inversion capacity and the inversion of R-(-)-ibuprofen after application of commercial and recrystallised racemic ibuprofen was nearly complete in this study. The effects of crystallinity on solubility in simulated media in vitro did not correlate to the findings on the extent of absorption in the rat in vivo.

Animals↗

PubMed1996

Lack of pharmacokinetic interaction between pantoprazole and diclofenac.

The new H+/K+ ATPase inhibitor pantoprazole is extensively metabolized by the liver. As substituted benzimidazoles may potentially interact with the cytochrome P450 system, the influence of pantoprazole on the pharmacokinetics of the NSAID diclofenac was investigated. Diclofenac is widely used in the treatment of rheumatic diseases and is mainly metabolized in the liver by CYP2C9. Twenty-four healthy volunteers (13 male/11 female) completed a randomized crossover study. As test they received orally 40 mg pantoprazole and concomitantly 100 mg diclofenac. As respective references 100 mg diclofenac or 40 mg pantoprazole were given alone. Diclofenac and pantoprazole serum concentrations were measured. Lack of pharmacokinetic interaction was handled as an equivalence problem. The 90% confidence intervals (CI) of the ratios of the primary characteristic AUC and the secondary characteristic Cmax of diclofenac were entirely within the equivalence range of 0.8-1.25. Hence, no influence of pantoprazole on the pharmacokinetics of diclofenac was concluded, either by competition with the CYP2C9 or by the reduction of gastric acid secretion. Vice versa, diclofenac did not affect the pharmacokinetics of pantoprazole. All treatments were safe and well tolerated. No dose adjustment is required during concomitant treatment with diclofenac and pantoprazole.

2-Pyridinylmethylsulfinylbenzimidazoles↗

PubMed1996

Lack of pharmacokinetic interaction between pantoprazole and diclofenac.

The new H+/K+ ATPase inhibitor pantoprazole is extensively metabolized by the liver. As substituted benzimidazoles may potentially interact with the cytochrome P450 system, the influence of pantoprazole on the pharmacokinetics of the NSAID diclofenac was investigated. Diclofenac is widely used in the treatment of rheumatic diseases and is mainly metabolized in the liver by CYP2C9. Twenty-four healthy volunteers (13 male/11 female) completed a randomized crossover study. As test they received orally 40 mg pantoprazole and concomitantly 100 mg diclofenac. As respective references 100 mg diclofenac or 40 mg pantoprazole were given alone. Diclofenac and pantoprazole serum concentrations were measured. Lack of pharmacokinetic interaction was handled as an equivalence problem. The 90% confidence intervals (CI) of the ratios of the primary characteristic AUC and the secondary characteristic C(max) of diclofenac were entirely within the equivalence range of 0.8 - 1.25. Hence, no influence of pantoprazole on the pharmacokinetics of diclofenac was concluded, either by competition with the CYP2C9 or by the reduction of gastric acid secretion. Vice versa, diclofenac did not affect the pharmacokinetics of pantoprazole. All treatments were safe and well tolerated. No dose adjustment is required during concomitant treatment with diclofenac and pantoprazole.

2-Pyridinylmethylsulfinylbenzimidazoles↗

PubMed1996

Pantoprazole has no influence on steady state pharmacokinetics and pharmacodynamics of metoprolol in healthy volunteers.

The new H+/K+ ATPase inhibitor pantoprazole, a substituted benzimidazole, is metabolized by the hepatic cytochrome P450 enzymes 2C19 or 3A4 and subsequently undergoes phase II metabolism. The widely used beta 1-adrenoreceptor-blocking agent metoprolol is metabolized via CYP2D6. The influence of pantoprazole on the pharmacokinetics of an orally administered zero order kinetics formulation (ZOK) of metoprolol was the objective of this study. Eighteen volunteers (9 female, 9 male, age 20-44 years) completed the randomized, double-blind crossover study. Each subject received either 95 mg metoprolol and placebo (reference (R)) or 95 mg metoprolol and 40 mg pantoprazole (test (T)) as oral doses (sid) for 5 consecutive days. On day 5 of each period serum concentrations of R- and S-metoprolol were determined and a treadmill ergometry was performed. The primary pharmacokinetic characteristics for extent and rate of absorption were AUC(0-24h) and % PTF, respectively. To assess the pharmacodynamic effect of metoprolol the excess area under the effect vs. time curve was calculated for heart rate during ergometry (AUCexHR). Point estimate and 90% confidence limits (CI) for the ratios of population medians of T and R were given. The respective point estimates (90% CI) of the ratios of both primary and secondary characteristics were entirely within the equivalence range of 0.80 and 1.25 for both enantiomers of metoprolol. Moreover, equivalence could be shown for the pharmacodynamic characteristic AUCexHR. Hence, it was concluded that pantoprazole does not interact with metoprolol pharmacokinetics or pharmacodynamics. Therefore, no dose adjustment of metoprolol during therapy with pantoprazole is necessary.

2-Pyridinylmethylsulfinylbenzimidazoles↗

PubMed1995

Comparison of the bioavailability of dexibuprofen administered alone or as part of racemic ibuprofen.

Two bioavailability studies of S(+)-ibuprofen (dexibuprofen) were conducted in healthy volunteers to define the relationship between the bioavailability of the drug after administration of dexibuprofen alone or as part of ibuprofen racemate. Enantioselective plasma drug analysis was used throughout. In the first study, the bioavailability of dexibuprofen from a 400 mg tablet formulation was compared with that from 400 mg in aqueous solution. The tablet formulation did not influence the bioavailability of the drug and dexibuprofen was well absorbed from the gastro-intestinal tract. The second study was divided into three identical parts. Bioavailability of dexibuprofen 200, 400 and 600 mg was compared with its bioavailability from ibuprofen racemate 400, 800 and 1200 mg. The second study showed that the mean relative bioavailability of dexibuprofen to ibuprofen racemate was 0.66, thus enabling the estimation of clinically useful dexibuprofen doses from the usual doses of the racemate. The 95% confidence interval limits did not include 0.5, leading to the conclusion that administering half of the racemate dose would not provide patients with an adequate amount of therapeutically active drug.

Adult↗

PubMed1995

Pharmacokinetics and bioavailability of different formulations of aciclovir.

The pharmacokinetics and bioavailability of aciclovir (CAS 59277-89-3) were examined after administration of newly developed 200 mg and 400 mg tablets. Two studies, each with 24 subjects of either sex, were performed. In the three-way study I, two different tablets containing 200 mg of aciclovir (test and reference products) and a short infusion of 250 mg aciclovir were compared. In the two-way study II, the bioequivalence of a newly developed 400 mg aciclovir tablet was tested against a standard product. Irrespective of dose, the peak plasma aciclovir levels were obtained 1.5 h after administration of the tablets. In the case of the 200 mg tablets, the mean Cmax-values were 454 ng/ml (pilot test formulation, T) and 525 ng/ml (reference formulation, R), whereas the mean Cmax-values after administration of the 400 mg tablets were 779 (T) and 800 (R) ng/ml for test and reference formulation, respectively. The mean AUC calculated to the time of the last measurement in each instance was in the order of 2290 (T) and 2275 (R) ng/ml x h (200 mg tablets) or 3726 (T) and 3855 (R) ng/ml x h (400 mg tablets). The amount of the dose renally excreted as unchanged aciclovir was measured at 20.8 (T) - 21.8 (R)% with the 200 mg tablets and 14.3 (T) - 15.1% (R) with the 400 mg tablets.(ABSTRACT TRUNCATED AT 250 WORDS)

Acyclovir↗

PubMed1994

Treatment of advanced colorectal cancer with folinic acid and 5-fluorouracil in combination with cisplatinum.

51 patients with metastatic colorectal cancer (stage Dukes D) were treated with intravenous (i.v.) infusion on days 1, 3, 5, 8 and 16 with folinic acid (200 mg/m2) and 5-fluorouracil (600 mg/m2), and on days 1, 8 and 16 with cisplatinum (25 mg/m2 i.v.); cycles were repeated every 4 weeks. All 51 patients were evaluable for toxicity and response criteria. 26 patients had objective responses (3 complete responses, 5.9%; 23 partial responses, 45.1%), relative risk 51% (95% confidence intervals 36.7-65.0%). Response duration ranged from 4 to 28.0 months (median 16.8). Overall median survival of all patients included was 14.7 months (range 3.0-33.0). Toxicity of WHO grade III, requiring dose reduction, occurred in 9 (18%) patients. The regimen described here appears to be active, safe and well tolerated for treatment of patients with advanced colorectal cancer.

Aged↗

PubMed1993

High-performance liquid chromatographic determination of total thiamine in human plasma for oral bioavailability studies.

A high-performance liquid chromatographic method for the determination of total thiamine in plasma was developed for a relative bioavailability comparison of two oral thiamine preparations. After separation of thiamine mono- and diphosphates with the phosphatase enzyme, the total thiamine was subjected to reversed-phase high-performance liquid chromatography, postcolumn oxidized to thiochrome with K3[Fe(CN)6], and detected by fluorescence. In the bioavailability study, 16 human subjects were put on a low-thiamine diet for 3 days. On the 2nd and 3rd days, 14 blood samples per subject and day were taken at the same times each day. Drug administration did not take place until the 3rd day. After deduction of the native concentrations of total thiamine detected on the 2nd day (mean value of approximately 7 ng/mL), the post-treatment pharmacokinetic parameters were determined (two different preparations, each with 200 mg of thiamine.HCl).

Adult↗

PubMed1993

Determination of total pyridoxal in human plasma following oral administration of vitamin B6 by high-performance liquid chromatography with post-column derivatization.

An HPLC method for determining total pyridoxal from plasma was developed for a relative bioavailability comparison of two oral vitamin B6 (pyridoxine HCl) preparations. After cleavage of the pyridoxal-5-phosphate with the acid phosphatase enzyme, the total pyridoxal was determined by HPLC. Pyridoxal was separated on a reversed-phase column, post-column derivatized to pyridoxal-semicarbazide, and then detected by fluorescence and quantitated. The limit of detection was 2 ng/mL and interday variation (3 days) over the whole concentration range (13-215 ng/mL spiked) was < 4.1%. In the relative bioavailability study, 16 human subjects were put on a low vitamin B6 diet for a period of 3 days. On the 2nd and 3rd days, 14 blood samples were taken per subject at the same times each day. The drug was administered on the 3rd day. Total endogenous pyridoxal detected on the 2nd day varied in plasma between 13 and 17 ng/mL. Pharmacokinetic parameters corrected for background are reported for two vitamin B6 (40 mg) preparations. Briefly, the pharmacokinetic results for the Ratiopharm preparation compared with the Hoffmann-La Roche preparation are, respectively: AUC0-24, 369.2 and 352.6 ng.h/mL; AUC24-48, 1638.2 and 1662.3 ng.h/mL; net Cmax, 193.0 and 197.1 ng/mL; tmax, 1.25 and 1.44 h; and relative bioavailability, 97.9% (Westlake, 88-112%).

Adult↗