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Biomedical subjects

B H Jensen

Publications and source records attributed to B H Jensen.

18 recordsLinked to original sources
PubMed1992

Multiple oral administration of a ketoprofen-dextran ester prodrug in pigs: assessment of gastrointestinal bioavailability by deconvolution.

Deconvolution has been applied to estimate the in vivo dissolution/release process of ketoprofen from a ketoprofen-dextran ester prodrug in pigs. The prodrug was given to three pigs at intervals of 12 hr and in seven doses corresponding to 4 mg ketoprofen/kg body weight. Frequent blood sampling was carried out at the first, third, and seventh intervals. Plasma steady-state concentrations of ketoprofen following the prodrug administration were between 2 and 4 micrograms/ml. The reference consisted of a single p.o. dose of parent ketoprofen (4 mg/kg body weight). For each pig the response following the multiple dosing was deconvolved with the reference response using an algebraic deconvolution procedure adopted from the literature. The obtained cumulated in vivo dissolution/release profiles revealed similar release rates for the three pigs and similar extents of release (59, 70, and 65%). The mean in vivo dissolution/release times (MDT) were calculated to be 5.4, 6.1, and 5.7 hr, respectively. In conclusion, following administration of the dextran prodrug the plasma concentration curves and the dissolution/release profiles are uniform, with small interindividual variations.

Administration, Oral↗
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↗
PubMed1991

Left ventricular peak filling rate, heart failure and 1-year survival in patients with acute myocardial infarction.

Radionuclide left ventricular (LV) peak filling rate (PFR) was determined in 185 survivors of acute myocardial infarction (AMI) and expressed in units of (1) end-diastolic volume per second (EDV s-1). (2) stroke volume per second (SV s-1), or (3) actual millilitres of blood filled into the left ventricle per second (ml s-1). The purpose of the study was to assess the interrelationship between the three expressions of PFR, and to analyse their significance with regard to signs of congestive heart failure and 1-year survival in patients with AMI. PFR EDV s-1, PFR SV s-1 and PFR ml s-1 had a poor relationship to each other, were all influenced by LV volumes and ejection fraction, and supplied contradictory information with regard to LV filling in patients with heart failure. None of the three expressions of LV peak filling rate had an association to heart failure that was independent of LV volume and ejection fraction. A low PFR EDV s-1 in contrast to a high PFR SV s-1 was associated with a high 1-year cardiac mortality, suggesting that these 'normalized' indices of LV peak filling rate signalled LV size and stroke volume rather than actual LV filling behaviour. No association was present between PFR ml s-1 and 1-year mortality. We conclude that the clinical use of radionuclide LV PFR in patients with AMI may lead to spurious results, unless the influence of LV size and ejection fraction is taken into consideration.

Diastole↗
PubMed1991

Stability of ketoprofen-dextran ester prodrugs in homogenates of various segments of the pig GI tract.

Initial velocities of ketoprofen formation from ketoprofen-dextran ester prodrugs incubated in homogenates of various segments of the pig GI-tract were determined. Enzyme-mediated drug release was found in caecum and colon homogenates with their contents, whereas release rates in the stomach, duodenum, jejunum and ileum homogenates were comparable to those determined in pure buffer solutions of identical pH. In colon homogenates adjusted to various pH values between 6.0 and 7.9, little variation in release rates was observed. However, the contribution of enzyme-catalyzed drug regeneration to the overall initial velocity of ketoprofen formation increased significantly as a function of decreasing pH. The presence of several antibiotics and betamethasone in colon homogenates did not affect the drug activation process, whereas the addition of various enzyme inhibitors slowed down the ketoprofen release rates. During incubation in colon homogenates the average molecular weight of the dextran esters decreased. The drug release may therefore involve an initial fragmentation of the drug-liganded dextran chains carried out by dextranases secreted from the microflora which reside in the pig's large bowel.

Animals↗
PubMed1991

Bioavailability of ketoprofen from orally administered ketoprofen-dextran ester prodrugs in the pig.

The bioavailability of ketoprofen after oral administration of aqueous solutions of various ketoprofen-dextran ester prodrugs in pigs was assessed. Conjugates derived from dextran fractions in the molecular weight range 10,000-500,000 were employed. Compared to the administration of an oral solution of an equivalent dose of parent ketoprofen, the average absorption fractions for the different prodrugs ranged from 100 to 67%. Relatively small inter-individual variation of ketoprofen bioavailability was observed. Apparently, the molecular size of the employed dextran transport group only has a minor influence on the pharmacokinetic parameters. The ketoprofen plasma profiles for all the administered prodrugs exhibited a characteristic lag time of ketoprofen appearance in the blood (2-3 h). Quite similar results were obtained from identical experiments carried out in the pig, employing naproxen-dextran esters. Thus, the present study adds support to a more versatile application of the dextran ester prodrug approach to providing selective colon delivery of drugs possessing a carboxylic acid functional group.

Administration, Oral↗
PubMed1991

Left-ventricular performance, volumes, and catecholamine responses during anaesthesia induction--monitoring by combined radionuclide cardiography and right heart catheterization.

Sequential radionuclide imaging and continuous recording of arterial and right heart pressures were carried out during anaesthesia with midazolam 0.2 mg kg-1, pancuronium 0.15 mg kg-1 and fentanyl 10 micrograms kg-1 in eight patients with normal cardiopulmonary status scheduled for craniotomy. The aim was to examine how a stress-free anaesthetic induction tailored to protect against the hypertension and tachycardia provoked by laryngoscopy and intubation influenced left-ventricular performance, left-ventricular loading conditions and plasma catecholamine concentrations. During the 20-min study period no significant changes were observed in heart rate, left-ventricular ejection fraction, ratio of peak systolic pressure to left-ventricular end-systolic volume, pulmonary capillary wedge pressure, left-ventricular end-systolic volume, cardiac output, dopamine and noradrenaline concentrations. Except for a minor increase in mean arterial pressure after laryngoscopy and intubation, mean arterial pressure decreased 24%, left-ventricular end-diastolic volume decreased 15%, and left-ventricular stroke volume decreased 21%. Central venous pressure increased by 75% but there was no parallel increase in pulmonary wedge pressure, which in turn did not reflect the alterations in ventricular end-diastolic volume. Plasma adrenaline concentrations decreased significantly (66%). The chosen induction regimen preserved global left-ventricular pump function during laryngoscopy and intubation without any activation of the sympathetic nervous system. Central venous and pulmonary wedge pressures were unreliable in the assessment of ventricular preload during induction of general anaesthesia.

Adult↗
PubMed1990

Left ventricular volumes in the recovery phase after myocardial infarction: relation to infarct location, left ventricular function and one-year cardiac mortality.

Absolute left ventricular volumes, normalized to body surface area, were determined by a count-based radionuclide technique in 189 patients with myocardial infarction (MI). All examinations were performed in the second week after MI. Fifty-three percent of the patients had an increased end-diastolic volume index (EDVI) and 72% an increased end-systolic volume index (ESVI). Patients with anterior MI had the same median EDVI as patients with inferoposterior MI, but significantly higher median ESVI and significantly lower median stroke volume index (SVI). SVI was subnormal in 19% of the 189 patients and left ventricular ejection fraction (LVEF) was subnormal in 67%. A non-linear, inverse relationship was present between EDVI and LVEF and between ESVI and LVEF, but LVEF varied greatly for any degree of ventricular dilatation. During a 1-year follow-up period, death from cardiac causes occurred in 29 patients. A strong relationship was present between the degree of ventricular dilatation and 1-year mortality, as well as between the degree of SVI or LVEF reduction and 1-year mortality but, next to clinical heart failure, LVEF was the single most powerful predictor of cardiac death, and various combinations of EDVI, ESVI and SVI did not add more prognostic information to that obtained by heart failure than did LVEF.

Aged↗
PubMed1989

Symptoms and signs of heart failure in patients with myocardial infarction: reproducibility and relationship to chest X-ray, radionuclide ventriculography and right heart catheterization.

102 patients with myocardial infarction (MI) were examined by three clinicians, who independently recorded the following symptoms and signs: dyspnoea, a displaced apex beat, S3-gallop, rales, neck vein distension, hepatomegaly, and dependent oedema. Chest X-ray, radionuclide ventriculography, and (in 40 patients) right heart catheterization were carried out immediately after the physical examination. The clinicians frequently disagreed as to the presence of physical signs of heart failure in individuals. Moreover, these signs were of limited value in identifying patients with pulmonary vascular congestion on chest X-ray, reduced left or right radionuclide ventricular ejection fractions, enlarged ventricular volumes or haemodynamic evidence of ventricular dysfunction. We conclude that clinicians frequently disagree in the recognition of physical signs of heart failure, and that these signs have an unpredictable relationship to radiographic, radionuclide and haemodynamic measures of ventricular performance in patients with MI. Nevertheless, physical signs are useful in identifying patients with high risk of cardiac death.

Adult↗
PubMed1987

Right and left ventricular ejection fractions: relation to one-year prognosis in acute myocardial infarction.

Right and left ventricular ejection fractions (RVEF and LVEF) were measured by radionuclide angiography in 423 patients with acute myocardial infarction (AMI). All investigations were performed at hospital discharge. Of 304 patients with first AMI, 26% had normal ejection fractions, 10% had a decrease in RVEF only, 46% a decrease in LVEF only, and 18% decrease in both RVEF and LVEF. Death from cardiac causes occurred in 52 patients in a one-year follow-up period. A reduced RVEF at hospital discharge had little, if any, relation to one-year mortality. In contrast, there was an inverse curvilinear relationship between LVEF and one-year cardiac mortality.

Adult↗
PubMed1986

Gas-producing infections after lower-limb amputation because of ischemia.

During the period 1972-1982, 22 patients with gas-producing infections after lower-limb amputation because of ischemia were reviewed. In 16 cases bacteria of the genus Clostridium could be cultured. Treatment consisted of hyperbaric oxygen, surgical debridement, and antibiotics. The incubation period was 1-11 days after the primary amputation, and the duration of the infection 2-31 days, significantly lower among 14 patients with diabetes mellitus. There was no difference in the course of clostridial and nonclostridial infections. No deaths were attributable to gas-forming infection.

Aged↗
PubMed1978

Glomerular filtration rate during enflurane anaesthesia.

Pre- and preoperative determination of glomerular filtration rate (GFR) was performed in 10 patients operated on during enflurane anaesthesia. The mean GFR decreased significantly by 21%. The decrease in GFR is of the same order of magnitude as that reported for most general anaesthetics.

Adult↗
PubMed1977

Glomerular filtration rate during halothane anaesthesia and epidural analgesia in combination with halothane anaesthesia.

Pre- and peroperative determination of glomerular filtration rate (GFR) was performed in nine patients operated during light halothane anaesthesia (group A) and in nine patients operated during epidural analgesia in combination with light halothane anaesthesia (group B). In group A, the mean GFR decreased insignificantly by 7% and the mean arterial blood pressure increased significantly by 10%. In group B, the mean GFR decreased significantly by 19% and the mean arterial blood pressure decreased significantly by 15%. It is suggested that the difference in change in GFR between the two groups was caused by differences in mean arterial blood pressure.

Adult↗