Biomedical subjects

S N Rasmussen

Publications and source records attributed to S N Rasmussen.

At least 37 records · Page 2Linked to original sources

PubMed1997

Hepatobiliary dysfunction and primary sclerosing cholangitis in patients with Crohn's disease.

BACKGROUND: Only a few studies have attempted to determined the prevalence of long-standing abnormal liver function and primary sclerosing cholangitis (PSC) in patients with Crohn's disease (CD). The aim of the study was to determine the prevalence of long-standing abnormal liver function test results and to describe the clinical, biochemical, and histologic findings in patients with large-duct classic PSC and small-duct PSC (that is, normal cholangiogram) in patients with CD during a 15-year period. METHODS: Patients with CD and long-standing abnormal liver function results were investigated individually with endoscopic retrograde cholangiography and liver biopsy. RESULTS: Of 262 consecutive patients with CD, 38 (15%) had long-standing increased alkaline phosphatase (ALP) values (mean, 1065 U/l; range, 321-4165 U/l). Of these, 10 patients were classified as having hepatic disease (4%), of which 9 had PSC and 1 had a non-specific reactive hepatitis. Of nine patients with PSC (3.4%), three were classified as having large-duct PSC; five, small-duct PSC; and one, unclassified. In patients with large-bowel CD (n = 102) the prevalence of PSC was 9%. Mean age at diagnosis of PSC was 35 years (22-46 years), and the female to male ratio, 7:2. All PSC patients had large-bowel involvement (P < 0.00015), and two of them developed colonic carcinoma of the large bowel (P < 0.01). All cases of small-duct PSC were stage 1, whereas large-duct PSC were stage 2-3. During the observation period (mean, 5.4 years) no PSC patients died. CONCLUSIONS: The results of our study indicate that PSC is the major hepatic disease in patients with CD and long-standing abnormal liver function tests and is approximately as prevalent as in ulcerative colitis. Patients with PSC and CD may have a milder liver disease than patients with PSC and ulcerative colitis, perhaps because large-duct PSC is less common in patients with CD. Cholangiograms and liver biopsies are both needed to evaluate the extent of the disease.

Adult↗

PubMed1996

Stereoselective pharmacokinetics of methadone in chronic pain patients.

Ten patients with chronic pain were randomized to an open, balanced, crossover study. Each patients received two different preparations of racemic methadone, i.e., tablets and intravenous infusion. The pharmacokinetic parameters of the R- and S-enantiomers of the racemate are reported. The analgesically active R-methadone has a significantly longer mean elimination half-life than the optical antipode S-methadone (t1/2 = 37.5 and 28.6 h, respectively). The mean total volume of distribution is 496.6 L for R-methadone and 289.1 L for S-methadone. Significant differences in the mean clearance between R- and S-methadone are seen (0.158 and 0.129 L/min, respectively). However, the lagtime after oral administration and the bioavailability did not show differences between the isomers. The data suggest that both enantiomers of methadone should be measured if correlations between pharmacodynamics and kinetics are made due to the stereoselective differences in half-life, total volume of distribution, and clearance.

Aged↗

PubMed1996

Assessment of the diagnoses of Crohn's disease and ulcerative colitis in a Danish hospital information system.

BACKGROUND: Our aim was to estimate the completeness-that is, whether all patients were included in the system-and the validity-that is, whether the diagnostic criteria were fulfilled for the patients registered-of the diagnoses of Crohn's disease and ulcerative colitis in a Danish hospital system. METHODS: Information in a regional hospital system, in the County of North Jutland, Denmark, was compared with hospital records and information in a pathology system. RESULTS: The analysis of the completeness included 143 patients with Crohn's disease and 285 patients with ulcerative colitis. The completeness of the regional hospital system using the pathology system as a reference standard was 94% for both diseases. The analysis of the validity included 281 patients registered as having Crohn's disease and 506 patients registered as having ulcerative colitis. The validity of the two diagnoses was 97% and 90%, respectively. CONCLUSIONS: The regional hospital system showed few misclassifications of the diagnoses of Crohn's disease and ulcerative colitis. Thus the nationwide hospital system (based on the regional hospital systems) may provide a unique study base for future research.

Colitis, Ulcerative↗

PubMed1996

Clinical pharmacology in gastroenterology: development of new forms of treatment of inflammatory bowel disease.

Kinetic-dynamic aspects of the development of slow-release mesalazine, Pentasa (now an established treatment of inflammatory bowel disease (IBD)), and cyclosporin, a T cell selective immunosuppressant (still in the investigative phase), are reviewed as examples of Danish contributions at an early stage to international, clinical drug research. Apart from increasing the therapeutic options for patients with IBD, current and future studies with these (and other) drugs may add important clues to a more precise understanding of the basic pathogenetic mechanisms (e.g. cytokines, adhesion molecules) involved in these diseases. The future development and clinical implementation of novel drug designs in IBD and other gastrointestinal diseases may be expected to benefit from a continued or even closer collaboration between clinical gastroenterologists and basic research institutions, including the pharmaceutical industry at an early stage.

Aminosalicylic Acids↗

PubMed1995

Assay of tocainide enantiomers in plasma by solid-phase extraction and indirect chiral high-performance liquid chromatography after derivatization with (-)-menthyl chloroformate.

A fast high-performance liquid chromatographic (HPLC) assay was developed for determination of tocainide enantiomers in plasma. Subsequent to solid-phase extraction of tocainide from plasma, homochiral derivatization with (-)-menthyl chloroformate enabled separation of the enantiomers by a conventional reversed-phase HPLC system. The detection was performed by UV absorption at 262 nm. An enantiomeric resolution of 1.0 was obtained. Linearity of the method was investigated and found to be good in the range from 1.0 to 20.0 micrograms/ml tocainide enantiomer and the limit of quantitation was 1.0 microgram/ml. The method was applied to a study of the distribution and elimination pharmacokinetics of tocainide enantiomers in the rabbit. No difference in distribution or elimination between the enantiomers was found nor did the enantiomers affect the disposition of one another when administered together as the racemate.

Animals↗

PubMed1995

Myocardial uptake kinetics of tocainide enantiomers in the isolated perfused rabbit heart.

The extent of myocardial accumulation of tocainide, administered as single enantiomers and as well as racemate, was determined in the isolated, spontaneous beating rabbit heart. The heart was retrogradely perfused at a constant rate and fractions of the perfusate were collected during and after infusion. Kinetic parameters for myocardial accumulation and disposition of tocainide were indirectly determined from drug concentration/time course in the outflow perfusate. No stereoselectivity in myocardial accumulation was observed. A two compartment model with mean half-lives for distribution and elimination of 0.60 and 3.78 min, respectively, was fitted to the accumulation and disposition data. At steady-state, tocainide enantiomers were accumulated about three times in the myocardium relative to the perfusion liquid.

Animals↗

PubMed1995

Bioavailability of controlled release mesalazine (5-ASA) preparations.

Salazosulfapyridine was generated by Nanna Svartz in 1941. Mesalazine (5-ASA) was demonstrated in 1977 to be the therapeutically active moiety of salazosulfapyridine. Since then, a number of alternatives to salazosulfapyridine have appeared: olsalazine and salicylazobensoic acid, which are as salazosulfapyridine azo-preparations. Also, pure mesalazine drugs have been developed: Asacol, Claversal, and Pentasa. Despite the many similarities of these pure mesalazine controlled-release drugs, there are also significant differences. Some of these are due to different pharmaceutical designs of the delivery principle. Other important parameters are gastrointestinal pH variations in the healthy and diseased gut, and variations in ventricular emptying and in intestinal transit patterns.

Aminosalicylic Acids↗

PubMed1994

Pharmacokinetics of tinzaparin (Logiparin)--a low molecular weight heparin--after single and repeated intravenous administration in rats.

After a single and repeated i.v. injections of 1 mg/kg 3H-radiolabelled tinzaparin once daily to rats for 7, 14, and 21 days, drug-related radioactivity in plasma, tissues, urine and faeces was measured by use of liquid scintillation counting. The decay in plasma could be described by a three-compartment model with half-lives of the two distributive phases and the terminal elimination phase of 15 min, 90 min, and 37 hrs, respectively. The peak plasma concentration did not change during repeated dosing, as opposed to the trough concentration which increased 3 fold. The decay in tissues was significantly different from that in plasma, and showed less fluctuations. Drug-related radioactivity accumulated gradually with repeated dosing, reaching accumulation ratios between 5 and 9, when based on trough concentrations. Slow elimination was observed from tissues, and significant amounts were still present 14 days after discontinuation of the repeated dosing. In the liver, the concentrations were almost constant during a dosing interval. After a single injection, 86% and 4% of the administered radioactive dose were excreted in urine and faeces over 7 days, respectively, the majority being recovered during the first 24 hrs, demonstrating that the major route of elimination was by renal excretion. The molecular mass distribution of radioactivity in urine was similar but not identical to the injected test substance. It was shifted slightly towards lower molecular mass and had no anti-factor Xa activity, suggesting that the heparin was either inactivated, presumably by desulphation, or that the antithrombin binding portion of the drug was cleared through a different route.

Animals↗

PubMed1994

[Sclerosing cholangitis and ulcerative colitis. Regional prevalence].

The aim of the study was to determine the prevalence of primary sclerosing cholangitis (PSC) in a regional population of patients with ulcerative colitis (UC). Three hundred and five patients with UC followed over a 12 year period were examined for elevations of serum alkaline phosphatase (> 280 U/l). Twenty four such patients were found. If no cause of these elevations were found by initial investigations, endoscopic retrograde cholangiography was performed in order to determine whether they had PSC. Eleven patients were found to have PSC (3.6%), of whom five had progressive disease, including two deaths from cholangio-carcinoma, during a six-year observation period. We found no certain relation between the extent, duration or activity of ulcerative colitis and the presence of PSC. Alkaline phosphatases were elevated up to 3.7 times the upper reference level, the aminotransferases were only found to be mildly elevated.

Adolescent↗

PubMed1994

Bioavailability of four oral coenzyme Q10 formulations in healthy volunteers.

The bioavailability of four different Coenzyme Q10 (CoQ) formulations was compared in ten healthy volunteers in a four-way randomised cross-over trial. The included formulations were: A hard gelatin capsule containing 100 mg of CoQ and 400 mg of Emcompress. Three soft gelatin capsules containing: 100 mg of CoQ with 400 mg of soy bean oil (Bioquinon); 100 mg of CoQ with 20 mg of polysorbate 80, 100 mg of lecithin and 280 mg of soy bean oil; and 100 mg of CoQ with 20 mg of polysorbate 80 and 380 mg of soy bean oil, respectively. The result suggests that the soya bean oil suspension of CoQ (Bioquinon has the highest bioavailability. A difference in basic AUC and AUC after p.o. administration of CoQ was observed with respect to sex. A characteristic two peak-pattern was observed at the concentration-time profile.

Administration, Oral↗

PubMed1994

Comparative bioavailability of 5-aminosalicylic acid from a controlled release preparation and an azo-bond preparation.

BACKGROUND: Knowledge of the bioavailability of 5-aminosalicylic acid (5-ASA, mesalazine) from the different 5-ASA-containing drugs is important for rational therapy of inflammatory bowel diseases. METHODS: The local and systemic bioavailability of 5-ASA from a controlled release 5-ASA preparation (Pentasa--2, 4 or 6 g/day) was investigated and compared with the azo-bond 5-ASA preparation olsalazine (Dipentum--2 g/day) in 13 healthy volunteers during steady state conditions. RESULTS: The therapeutically relevant parameter of 5-ASA at the rectal level, expressed as the mean concentration in faecal water, showed a significant trend towards higher concentrations with increasing Pentasa dose: 9.2 mmol/L, 19.0 mmol/L and 24.4 mmol/L, respectively. The concentration of olsalazine 2 g/day was 16.0 mmol/L. The concentration of the metabolite N-acetyl-5-aminosalicylic acid (Ac-5-ASA) did not rise with increasing Pentasa dose, indicating saturable presystemic acetylating capacity of 5-ASA. Total urinary excretion of 5-ASA and Ac-5-ASA, as a percentage of the daily ingested 5-ASA dose, remained constant on the three Pentasa doses, but there was a significant increase in the 5-ASA fraction. Mean steady state plasma concentrations of 5-ASA and Ac-5-ASA were significantly higher on Pentasa 4 g/day and 6 g/day than on 2 g/day. Values on Pentasa 2 g/day were comparable with those on olsalazine 2 g/day. CONCLUSIONS: The study confirmed that 5-ASA is released from Pentasa in a predictable manner, the amount released increasing with dose. Olsalazine is an excellent generator of 5-ASA in the colon.

Administration, Oral↗

PubMed1994

Effect of omeprazole and sucralfate on prepyloric gastric ulcer. A double blind comparative trial and one year follow up.

This study compared healing rates, relief of symptoms, frequency of adverse events, and proportion of patients in remission after one year follow up in 104 patients with active prepyloric ulcer during treatment with 40 mg omeprazole once daily or 2 g sucralfate twice daily, using a randomised double blind controlled trial. Healing rates after two, four, and six weeks were (omeprazole/sucralfate) 49%/23%; 83%/59%; 90%/70% respectively. After two weeks, omeprazole was more efficient than sucralfate in relief of daytime and nocturnal epigastric pain, nausea, and heartburn. The proportion of patients in remission after one year follow up was significantly higher in the omeprazole group (p < 0.01). Of the healed patients ulcers recurred in 36% in the omeprazole group and in 46% in the sucralfate group. It is concluded that the ulcer healing rate was higher and symptom relief was more pronounced in the omeprazole group compared with the sucralfate group, and that more patients were still in remission after a one year follow up period.

Adult↗

PubMed1994

Specificity of the imino acid carrier in rat small intestine.

The rat intestinal imino acid carrier is chloride independent, while in guinea pig and rabbit intestine it is chloride dependent. While non-alpha-amino acids do not significantly interact with guinea pig and rabbit imino acid carriers, inhibition studies had indicated that in rat small intestine beta-alanine, gamma-aminobutyric acid (GABA), and probably taurine might be transported by the imino acid carrier. The present study of rat jejunum demonstrates that the half-maximal activation concentration of beta-alanine (K1/2 beta-Ala) is identical to its inhibition constant (Ki beta-Ala) against GABA, that K1/2GABA is identical to KiGABA against beta-alanine, that proline and sarcosine have identical values of Ki against beta-alanine and GABA, and that Ki of beta-alanine and proline against sarcosine are equal to their K1/2 values. Taurine inhibits the transport of beta-alanine, and 300 mM proline and beta-alanine reduce the transport of taurine measured at 80 mM taurine to the level expected for the diffusive contribution, corresponding to Ki values equal to those against sarcosine. Thus the rat imino acid carrier is the principal carrier of taurine and the only carrier of beta-alanine and GABA. It is also demonstrated that alpha-amino-monocarboxylic acids with side chains in excess of one methyl group do not significantly interact with the imino acid carrier, and the lack of stereospecificity is confirmed.

Alanine↗

PubMed1994

Disposition of 5-aminosalicylic acid and N-acetyl-5-aminosalicylic acid in fetal and maternal body fluids during treatment with different 5-aminosalicylic acid preparations.

STUDY OBJECTIVE: To determine the concentration of 5-aminosalicylic acid (5-ASA) and the metabolite N-acetyl-5-aminosalicylic acid (Ac-5-ASA) in the maternal and fetal plasma at delivery and in the maternal milk post partum. DESIGN AND STUDY SUBJECTS: Pregnant and lactating women with chronic inflammatory bowel disease, treated with different pure 5-ASA preparations participated in the study. At delivery, samples of fetal and maternal plasma were obtained from nine women. The excretion in milk was measured and the time of medicine intake was registered during a 24 h period 2-4 weeks after delivery in 13 women. RESULTS: Concentrations of 5-ASA in the fetal plasma were lower than in maternal plasma. Plasma concentrations of Ac-5-ASA were detectable in all the nine samples and similar levels in the mother and the fetus were found at the time of delivery. In three women 5-ASA was detected in the milk in low concentrations. The concentration of Ac-5-ASA in the milk varied considerably during the 24 h collection period, and also between individuals; its concentration tended to be higher than in the plasma. No time relation between medicine intake and maximal concentration in the milk was found. Based on the maximal Ac-5-ASA concentration and a milk intake of one liter/daily, the newborn receives less than 15 mg Ac-5-ASA daily. CONCLUSION: The study indicates that treatment with pure 5-ASA preparations in conventional doses is without risk to the fetus and the newborn.

Aminosalicylic Acids↗

PubMed1994

Effect of olsalazine and mesalazine on intraluminal pH of the duodenum and proximal jejunum in healthy humans.

BACKGROUND: Treatment of inflammatory bowel disease with olsalazine causes diarrhoea in 10% of patients. This is claimed to be caused by a drug effect on mucosal transport in the small intestine, which might be reflected in the intraluminal pH. We aimed to study the effect on jejunal pH of olsalazine (Dipentum) and an alternative preparation, slow-release mesalazine (Pentasa). METHODS: Thirteen healthy volunteers, seven male and six female, participated in a randomized, crossover study. Steady-state conditions were obtained after ingestion of 2 g or 6 g mesalazine daily or 2 g olsalazine daily for 1 week. The pH of the duodenum and proximal jejunum was measured by using pH-sensitive, radiotransmitting capsules, the location of which was confirmed by fluoroscopy. RESULTS: No effect of either drug on duodenal pH was detected. Mean duodenal pH ranged from 6.18 to 6.22. The mean pH of the pre-medication proximal jejunum was 6.02. Mesalazine had no significant effect, but olsalazine significantly increased the pH of the proximal jejunum (mean pH, 6.47). CONCLUSIONS: Our results indicate that the effect of olsalazine on jejunal transport of electrolytes and water, observed in experimental studies, also applies to human subjects in steady-state conditions, and adaptation does not occur within 6 days.

Adolescent↗

PubMed1994

Pharmacokinetics of 1 alpha-hydroxycholecalciferol after intraperitoneal, intravenous and oral administration in patients undergoing peritoneal dialysis.

Intravenous (i.v.) injection of vitamin D3 has a well known suppressive effect on the release of parathyroid hormone. However, the i.v. route is inconvenient in patients undergoing peritoneal dialysis. Moreover, no study has been published on the pharmacokinetics of 1 alpha-hydroxycholecalciferol (1 alpha-OHD3) after intraperitoneal (IP), i.v. and oral administration. Therefore, the appearance of 1,25-(OH)2D3 after administration of 1 alpha-OHD3 was studied in 8 peritoneal dialysis patients. Open, prospective, randomized cross-over design with single doses of 1 alpha-OHD3 (80 ng/kg BW) given on 3 separate occasions either IP, i.v. or oral was applied. After the administration of 1 alpha-OHD3, blood was collected at baseline and 0.5, 1, 2, 3, 4, 6, 12 and 24 h for measurement of circulating 1,25-(OH)2D3. A one compartment model with first order absorption and elimination (Cpl = Be-ke*t-Ae-ka*t) was fitted to the concentrations following i.v. administration. Following IP and oral administration the concentrations did not reach maximum levels within the time of blood sampling. In all cases, the 24 h area under the time/concentration curve for 1,25-(OH)2D3 (AUC24) was calculated using the trapezoidal method. Residual areas were calculated using the terminal slope from i.v. administration, and added to AUC24 giving AUC0-->infinity. After i.v. administration A, ka, B, ke, t1/2, AUC24 and AUC0-->infinity were (mean +/- SD) 62.9 +/- 16.4 pg/ml, 0.76 +/- 0.30 h-1, 71.6 +/- 14.7 pg/ml, 0.017 +/- 0.015 h-1, 109.4 +/- 129.5 h, 1315.8 +/- 236.9 pg/ml x h and 10322.2 +/- 11473.7 pg/ml x h, respectively.(ABSTRACT TRUNCATED AT 250 WORDS)

Administration, Oral↗

PubMed1993

Pharmacokinetics of recombinant factor VIIa in the rat--a comparison of bio-, immuno- and isotope assays.

Recombinant human factor VIIa (rFVIIa) is an activated coagulation factor for intravenous use as a haemostatic agent in haemophiliacs who generate antibodies against factor VIII or IX. Plasma kinetic studies are important for the understanding of the action of rFVIIa which is exerted in the vascular compartment of the body, more specifically on the vessel walls at the site of injury. In the present study, rats were dosed 100 or 500 micrograms/kg 125I-rFVIIa i.v., without any side effects being observed, and the plasma profile of rFVIIa was studied by 3 different assays that were shown to correlate well at early times post-dose: trichloroacetic acid (TCA)-precipitable drug-related radioactivity, rFVIIa antigen determination by ELISA technique, and the assay of clot activity which is the only clinically applicable assay. The plasma concentration curve could be resolved into 1-3 exponentials, depending on the FVIIa detection principle that was employed. Initially, there was a short (ca. 10 min) phase of increasing concentrations before the attainment of Cmax. This was followed by a plasma recovery (Cmax x plasma volume/dose) in the vicinity of one half of the administered dose. The initial volume of distribution (V1) corresponded to the vascular compartment whereas the volume of distribution at steady state (Vss) was somewhat larger. Whole body clearance (CL-B) of rFVIIa was approx. 1 ml/min per kg, and mean residence time (MRT) and the half-life assumed to be associated with the loss of biological activity was approx. 1 h and 20-45 min, respectively.(ABSTRACT TRUNCATED AT 250 WORDS)

Animals↗

PubMed1993

Bioavailability of 5-aminosalicyclic acid from slow release 5-aminosalicyclic acid drug and sulfasalazine in normal children.

The bioavailability of a controlled release 5-aminosalicyclic acid preparation (Pentasa) was investigated in nine healthy children after a medication period of six days (1000 mg/day) and compared with sulfasalazine (Salazopyrin) (2000 mg/day). The local bioavailability in the distal gut lumen, reflected by the 5-aminosalicylic acid concentration in the fecal water, showed comparable values after Pentasa (4.44 mmol/liter) and Salazopyrin (6.25 mmol/liter). The concentration of N-acetyl-5-ASA was significantly higher after Pentasa, reflecting the more proximal release of 5-aminosalicyclic acid compared with Salazopyrin. No relation was found between the 5-aminosalicylic acid fecal water concentration water concentration and the 5-aminosalicylic acid dose per kilogram of body weight. The urinary excretion of 5-aminosalicylic acid and N-acetyl-5-aminosalicylic acid was higher after Pentasa than after Salazopyrin (32% vs 25%). Dose interval plasma concentration curves showed low values after both preparations. Based on the concept that the fecal water concentration is decisive for the efficacy of 5-aminosalicylic acid in distal inflammatory bowel disease, Pentasa treatment offers a relevant alternative in cases of Salazopyrin intolerance or allergy in children. The higher systemic bioavailability from Pentasa warrants monitoring of the renal function.

Aminosalicylic Acids↗