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S N Rasmussen

Publications and source records attributed to S N Rasmussen.

At least 19 recordsLinked to original sources
PubMed1992

Single-dose and steady-state pharmacokinetics of diltiazem administered in two different tablet formulations.

Single-dose and steady state pharmacokinetics of diltiazem administered in two different oral formulations were assessed with particular reference to rate and extent of absorption. Following single dose administration a significant difference in tmax was observed (2.9 +/- 1.9 and 6.8 +/- 2.6 hr respectively) whereas differences in AUC, t1/2 and Cmax were not significant. The AUC (mean +/- S.D.) values following single dose administration of Cardil and Cardizem were 678.4 +/- 321.5 and 948.6 +/- 580.6 ng.ml-1.hr respectively. The mean and the 95% confidence limits for the observed ratio AUCCardil/AUCCardizem are 0.89 and 0.44-1.34 respectively. At steady-state a significant difference between Cmax/Cmin and tmax was seen Cmax/Cmin being 4.9 and 3.2 respectively and Tmax being 2.7 +/- 2.0 and 6.0 +/- 2.8 hr respectively, whereas Cmax and AUC did not differ significantly. The AUC (mean +/- S.D.) values in steady state of Cardil and Cardizem were 880.1 +/- 399.8 and 1056.8 +/- 509.8 ng.ml-1.hr respectively. The mean and the 95% confidence limits for the observed ratio AUCCardil/AUCCardizem are 0.96 and 0.66-1.26 respectively. Although the observed ratios AUCCardil/AUCCardizem in both the single-dose and the steady-state study do not differ significantly from 1.0, the confidence limits exceed the acceptable values given by Poulsen & Juul (personal communication 1990) (a 20% decrease or increase of the ratio to 0.8 or 1.2).

Absorption↗
PubMed1992

Primary sclerosing cholangitis in patients with ulcerative colitis.

The prevalence of primary sclerosing cholangitis (PSC) in patients with ulcerative colitis (UC) attending the Depts. of Medical and Surgical Gastroenterology, Aalborg Hospital, during a 12-year period, was determined. All patients with an alkaline phosphatase (ALP) value above the normal range were investigated. Of 305 patients with UC, 24 patients had elevated ALP values, and 11 of these (3.6% of the study population), 4 males and 7 females, were found to have PSC by direct cholangiography. In five patients the disease worsened (two patients died of cholangiocarcinoma), in four it was stationary, and in two patients the disease improved during a mean observation period of 6 years. No differences in location of disease, disease activity, or duration of disease were found between patients with UC and PSC and patients with UC without PSC. The ALP values were raised to a mean of 3.7 times the upper normal limit (observed range, 1.5-5.5 times the upper normal limit). Aspartate aminotransferase was moderately elevated in most patients, but no other abnormal biochemical liver test results were observed at onset. The results of our study indicate that PSC is the major cause of raised ALP values in patients with UC; thus cholangiography should be performed in UC patients with unexplained elevated ALP levels. A prognostic indicator is needed to predict the individual prognosis and to determine the optimal timing of liver transplantation.

Adolescent↗
PubMed1991

[Primary sclerosing cholangitis].

Primary sclerosing cholangitis (PSC) is an uncommon disorder of unknown etiology, characterized by chronic inflammation and fibrosis of the intra- and extrahepatic bile ducts. PSC is commonly associated with chronic inflammatory bowel disease, especially ulcerative colitis, and often in younger men with an extensive colitis. The diagnosis is made by endoscopic retrograde cholangiography. The characteristic findings are multiple strictures and dilatations of the intra- and extrahepatic bile ducts. Patients with PSC usually have a cholestatic biochemical profile. The liver biopsy findings are often non-specific. Different survivals in these patients have been described. However, asymptomatic patients seems to have a more favorable prognosis. The only curative treatment is liver transplantation.

Cholangitis, Sclerosing↗
PubMed1991

Pharmacokinetics of 5-aminosalicylic acid in man following administration of intravenous bolus and per os slow-release formulation.

The fate of 5-aminosalicylic acid (5-ASA), which is used in the treatment of chronic inflammatory bowel diseases, was studied in six healthy volunteers receiving doses of 100 mg and 250 mg intravenous bolus as well as 250 mg per os (slow release). Following intravenous administration, the drug was rapidly eliminated with a plasma half-life of about 40 min, mainly due to rapid metabolism. No parent drug was recovered in feces, and the total recovery following oral administration (30%) was significantly lower than following the intravenous doses (77% and 72%). Nonlinear pharmacokinetics were suggested as the 2.5-fold increase in intravenous dose was followed by a significant relative increase (greater than 2.5) in the renal elimination of 5-ASA, as well as a significant decrease (less than 2.5) in the elimination of the metabolite N-acetyl-5-ASA. There was also a trend towards a decreasing total body clearance and metabolic ratio. The present study confirms earlier findings on the pharmacokinetics of 5-ASA and suggests a possible saturation of the N-acetylating system in the dose range studied. This may be of interest in the design of controlled-release formulations and dosage regimes for the treatment of diseases of the small-bowel, where 5-ASA is easily absorbed. Further, for the first time, a marked difference in the intestinal fate compared to the systemic fate of the drug is demonstrated, suggesting alternative presystemic metabolism of 5-ASA, which may bear relevance to its mode of action. Further studies on the pharmacokinetics of 5-ASA, preferably in patients, are warranted.

Administration, Oral↗
PubMed1991

Availability of mesalazine (5-aminosalicylic acid) from enemas and suppositories during steady-state conditions.

The local and systemic bioavailability of a mesalazine enema (Pentasa, Ferring A/S, Denmark) and a mesalazine suppository (Pentasa, Ferring) was assessed during steady-state conditions. Eleven healthy subjects took 1 g of the enema or the suppository twice daily for 1 week, with a drug-free period of at least 1 week in between. At the end of each treatment period the urine and faeces were collected for 48 h, and the concentrations of mesalazine and the metabolite acetyl-mesalazine were measured. Plasma concentrations of drug and metabolite were measured hourly during a 12-h dose interval. The faecal water concentration of mesalazine was significantly higher after suppository treatment (55.7 mmol/l) compared with enema treatment (31.7 mmol/l) (p less than 0.01). The systemic absorption was low; 15% of daily mesalazine dose was recovered in urine after enema treatment and 10% after suppositores (p less than 0.01). Plasma concentrations were low, and no accumulation of either mesalazine or acetyl-mesalazine occurred. In conclusion, the enema and the suppository can be continuously administered as 1 g of mesalazine twice daily, respectively, giving high faecal water concentrations of mesalazine and a low systemic absorption.

Administration, Rectal↗
PubMed1991

Absorption profiles of rectally administered midazolam estimated by deconvolution.

UNLABELLED: An algebraic deconvolution procedure adopted from the literature has been used to estimate the absorption profiles of rectally administered midazolam (0.3 mg/kg) in 8 healthy subjects. The extent of absorption estimated by the conventional AUC approach has previously been published and was compared to the deconvolution results. In the original study the sampling period was 840 min. When a deconvolution approach is used there may be no need to sample after the absorption is completed. Thus in this communication only samples drawn within the first 120 min and 300 min were used. The bioavailability estimated by the AUC ratio (mean 0.52 +/- SDrel 16%) is compared to the deconvolution results obtained using only data points within 120 (0.46 +/- 22%) (p = 0.02) and 300 min (0.51 +/- 20%) (p = 0.6) after drug administration. The absorption is almost complete after 120 min. Regarding the absorption rates 40% (range 27.55%) of the dose is absorbed after 60 min. The relative (normalised) absorption profiles showed that 79% (range 63-90%) of the maximum absorbed amount is absorbed within 60 min. IN CONCLUSION: Information regarding the rectal absorption of midazolam can be obtained from a sampling period of approximately 5 hours using the deconvolution approach. The algorithm used is relative easy to implement and is very easy to use with polyexponential parameters obtained by curve fitting as input.

Administration, Rectal↗
PubMed1990

Ion concentration and haematocrit as determinants of impedance in an erythrocyte suspension model of renal medullary tissue.

In order to analyse the respective roles of ion concentration and fractional volume of the interstitial compartment as determinants of the impedance, Z, of renal medullary tissue, a model was needed in which both these factors could be varied independently. An array of blood cell suspensions ions in saline (different haematocrit values and different NaCl concentrations) was used for this purpose. It was found that: (i) up to a measuring frequency of about 10 kHz, the complex consisting of needle electrodes and 'tissue' can be regarded as serially connected resistances, R, and capacitances; (ii) the frequency range 3-10 kHz can be regarded as optimal since it simultaneously assures low electrode polarization and a negligible role of tissue capacitance; (iii) increasing the haematocrit had two consequences--a reduced contribution of polarization impedance to the total impedance measured and a decreased sensitivity of ion concentration measurement from R-1 (conductance); (iv) passive electrical properties of renal medullary tissue were close to those of a 75% haematocrit cell suspension; (v) since in high haematocrit suspensions the resistive component of impedance predominates, within the frequency range 3-10 kHz either conductance or admittance, Z-1, can be used as an index of ion concentration; and (vi) impedance changes in kidney tissue are primarily determined by fluctuations of ion concentration with a less important contribution from interstitial volume changes.

Animals↗
PubMed1990

Measurement of gastrointestinal pH and regional transit times in normal children.

Gastrointestinal pH and regional intestinal transit times of a capsule were measured in twelve healthy children aged 8-14 years using a radiotransmitting pH-sensitive capsule. The location of the capsule was determined by fluoroscopy. pH in the stomach was 1.5, but rose to 6.4 in the duodenum (mean values). pH gradually rose in the small intestine and reached an alkaline peak value of 7.4 in the distal part. pH dropped to 5.9 in the cecum but rose to 6.5 in the rectum. Median gastric residence time of the capsule was 1.1 h. Small intestinal transit time was 7.5 h, and colonic transit time was 17.2 h. pH profile and intestinal transit times found in the present study are almost identical to values found in studies on healthy adults. It is therefore concluded that the release pattern of pH-dependent sustained-release tablets in children is likely to be equal to that of adults.

Adolescent↗
PubMed1990

Gastrointestinal pH and transit times in healthy subjects with ileostomy.

Gastrointestinal pH in 11 healthy subjects with ileostomy was determined with a pH-sensitive, radiotransmitting capsule. Median pH was 7.0 in duodenum, dropped to pH 6.3 in the proximal part, but rose to 7.3 in the distal part of the small intestine. In five subjects the pH of the ileostomy effluents was determined with the pH capsule as well as with a pH meter. Median pH was 7.2 measured with the capsule and 7.4 with the pH meter. The difference between the results obtained with the two methods ranged from 0.1 to 0.3 pH units. The median gastrointestinal transit time of the capsule was 10.5 h (range 6.2-12.8 h). Gastric residence time was 0.6 h (range 0.2-3.8 h), and small intestinal transit time was 10.3 h (range 5.6-11.9 h). Thus the small intestinal transit time in ileostomates is slightly increased compared with values reported from studies on subjects with intact gut. However, no statistically significant correlation was found between the small intestinal transit time and the time elapsed after the creation of the ileostomy. We conclude that colectomy does not alter small intestinal pH but seems to increase the small intestinal transit time of single units.

Adult↗
PubMed1990

Topical and systemic availability of 5-aminosalicylate: comparisons of three controlled release preparations in man.

The bioavailability of three pure 5-aminosalicylic (5-ASA) preparations (Asacol, Claversal, and Pentasa) was studied in 8 ileostomy patients and 12 normal subjects after 6 days of treatment with 2000 mg 5-ASA. The local bioavailability, reflected by the 5-ASA concentration was thereby measured at two clinically relevant areas of the gut: at the entrance to, and the exit from the colon. Estimates of the systemic bioavailability were obtained from the urinary excretions and the plasma values of 5-ASA and Acetyl-5-ASA (Ac-5-ASA) during the three regimens. The three preparations studied are designed to release 5-ASA at different levels in the intestine, but there was no significant difference in the 5-ASA concentrations in the ileostomy effluents (Asacol 1.8 mmol/L, Claversal 3.4 mmol/L, Pentasa 2.0 mmol/L, median values). However, we found a smaller urinary excretion of 5-ASA and Ac-5-ASA (5.2% vs Claversal 27.9% and Pentasa 23.0%, median values of ingested daily dose) and a lower concentration of Ac-5-ASA in the ileostomy effluents after Asacol treatment (0.8 mmol/L, median value) which indicates a more distal release from this preparation compared with Claversal (2.4 mmol/L, median value) and Pentasa (5.5 mmol/L, median value). In normal subjects a higher faecal water concentration of 5-ASA was found after Asacol (9.8 mmol/L, median value) compared with Claversal (5.0 mmol/L, median value), whereas no difference between the faecal water concentrations of Ac-5-ASA was found (Asacol 21.5 mmol/L, Claversal 21.6 mmol/L, median values). This can be explained by a larger systemic absorption of 5-ASA from Claversal, and accordingly Claversal treatment resulted in the largest urinary excretion of 5-ASA and Ac-5-ASA (43.7% vs Asacol 35.6% and Pentasa 31.6%, median values of ingested daily dose). The high Ac-5-ASA concentration in the ileostomy effluents and in the faeces after Pentasa, and the low plasma values, indicate a slow 5-ASA release from this preparation throughout the small and large intestine. The results of the study indicate that Asacol is released in the distal part of the small intestine, that Pentasa is gradually released in the small and large intestine, and that Claversal shows an intermediate release pattern.

Administration, Topical↗
PubMed1990

Renal tissue impedance: responses of the real and imaginary component to experimental variations in medullary electrolytes.

In order to assess the renal corticomedullary electrolyte gradient, electrical impedance (zeta) and phase angle (phi) were measured in the in-situ kidney of anaesthetized rats. A set of platinum/iridium needle electrodes was used, and the frequency (f) of the measuring current was varied between 0.5 and 50 kHz. zeta and its imaginary component (chi c) fell sharply as f increased from 0.5 to 3.5 kHz, and then decreased slowly or stabilized, whereas the real component (R) decreased progressively over the entire f range. Ion concentration in the renal medulla was experimentally lowered by administration of furosemide or hypertonic mannitol or by inducing a haemorrhage, and raised by infusing hypertonic NaCl solution. Both R and chi c varied inversely with tissue electrolyte concentration. Raising f from 3.5 to 10 and further to 20 kHz did not significantly amplify the changes in zeta. Within this frequency range R was not a more sensitive index of tissue electrolyte changes compared with overall zeta-value. The results verify previous empirical data indicating that changes in medullary tissue electrolytes can be dynamically estimated by monitoring tissue impedance.

Animals↗
PubMed1990

Plasma prekallikrein as a prognostic indicator in chronic liver insufficiency.

The prognostic value of plasma prekallikrein activity, prothrombin time, and serum albumin with regard to survival in chronic liver insufficiency was evaluated in 21 consecutive patients. Twenty patients had liver cirrhosis, and one patient had malignant liver disease (hepatocellular carcinoma). Eight patients died between 4 and 43 days after the time of blood sampling. These patients had a prekallikrein value less than 0.42. There were no overlapping prekallikrein values between patients who died and patients who survived (overlap index 0; p less than 0.001). Overlap index for prothrombin time was 0.35 (p less than 0.02), and for serum albumin 0.34 (p less than 0.02). In conclusion, plasma prekallikrein seems to indicate whether death is imminent in patients with liver insufficiency due to cirrhosis. Longitudinal studies of prekallikrein activity in different subgroups of patients with chronic and acute liver disease are recommended.

Adult↗
PubMed1990

Relative bioavailability of (+/-)-verapamil hydrochloride administered in tablets and chewing gum.

The absorption of verapamil administered orally in chewing gum (23.4-29.7 mg) and perorally in tablets (80 mg) to seven healthy volunteers in a study using an open cross-over design, was compared. Following peroral administration the mean +/- SD AUC/D was (5.4 +/- 1.9) x 10(-3) micrograms ml-1 h per microgram dose and after administration of chewing gum (6.6 +/- 2.3) x 10(-3) micrograms ml-1 h per microgram dose (NS). The AUC ratio of verapamil to the metabolite norverapamil was 1.5 after oral and 0.8 after peroral administration, indicating that a part of the verapamil administered in chewing gum was absorbed through the oral mucosa.

Adult↗
PubMed1990

Relative bioavailability of methadone hydrochloride administered in chewing gum and tablets.

Methadone administered in chewing gum in doses of 16.7-22.6 mg to seven patients in a study using an open balanced cross-over design, was compared with 20 mg of methadone given perorally as tablets. There was no significant difference in the AUC/D obtained after administration of chewing gum and tablets (p greater than 0.05). It is concluded that the chewing gum formulation should be considered for further testing with respect to suppression of abstinence syndrome in narcotic addicts.

Adult↗
PubMed1989

A placebo-controlled, double-blind, randomized trial of cyclosporine therapy in active chronic Crohn's disease.

We randomly assigned 71 patients with active chronic Crohn's disease who were resistant to or intolerant of corticosteroids to treatment with oral cyclosporine (5 to 7.5 mg per kilogram of body weight per day) or placebo for three months. Disease activity was assessed on a clinical grading scale without knowledge of the treatment given. At the end of the treatment period, 22 of the 37 cyclosporine-treated patients (59 percent) had improvement, as compared with 11 of the 34 placebo-treated patients (32 percent) (P = 0.032). During cyclosporine treatment, there was significant improvement in plasma orosomucoid levels (P = 0.0025) and the Crohn's Disease Activity Index (P = 0.00012). The effect of treatment became evident after two weeks. In the subsequent three months, during which the patients were gradually withdrawn from treatment, the improvement continued in 14 of the 37 patients (38 percent) in the cyclosporine group and in 5 of the 34 (15 percent) in the placebo group (P = 0.034). No serious adverse events were observed. We conclude that cyclosporine has a beneficial therapeutic effect in patients with active chronic Crohn's disease and resistance to or intolerance of corticosteroids.

Administration, Oral↗