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Biomedical subjects

M Ehrnebo

Publications and source records attributed to M Ehrnebo.

At least 19 recordsLinked to original sources
PubMed1991

A controlled study of low and high volume anesthetic jelly as a lubricant and pain reliever during cystoscopy.

To evaluate the influence of the volume of 2% lidocaine jelly as an anesthetic during cystoscopy 241 men and women received either 11 or 20 ml. jelly intraurethrally in a randomized, double-blind fashion. Pain was recorded on a visual analogue scale by the patient and on a 3-level scale by the physician. The pain scores according to the visual analogue scale were significantly higher in the patients given 11 ml. jelly than in those given 20 ml. when all patients in the study were analyzed. There was no significant difference in the visual analogue scale between the 2 treatments in women but a significant difference was noted in men, although in men older than 55 years the difference was not statistically significant. There was general agreement between the visual analogue scale results and the physician scores but the visual analogue scale procedure was more sensitive in detecting differences between treatments. It is suggested that approximately 11 ml. 2% lidocaine jelly is the appropriate volume for women and 20 ml. is the appropriate volume for men during cystoscopy but that the lower volume of jelly may be sufficient in older men.

Aging↗
PubMed1989

Pharmacokinetic and metabolic studies of high-dose busulphan in adults.

The pharmacokinetics of high-dose busulphan was studied in adult patients with acute myeloblastic leukaemia after oral doses of 1 mg.kg-1 every 6 h for 4 days. The mean steady-state plasma concentration was 1080 ng/ml-1 during the treatment. Individual steady-state concentrations after the last dose on average were 32% lower than those predicted from total AUC measurements following the first dose. Mean elimination half-life in plasma was 2.3 h after the last dose and 3.4 h after the first dose which suggests that busulfan may increase its own metabolic rate on repeated treatment. The cerebrospinal fluid/plasma concentration ratio of busulphan was 1.3. Busulphan showed insignificant protein binding in plasma (7.4%). About 2% of the dose was excreted unchanged in the urine. For the first time sulpholane, 3-hydroxysulpholane and tetrahydrothiophene 1-oxide were identified as urinary metabolites of busulphan in man.

Adult↗
PubMed1989

Care of pressure sores: a controlled study of the use of a hydrocolloid dressing compared with wet saline gauze compresses.

An occlusive hydrocolloid dressing (Comfeel Ulcus) was compared with a conventional wet saline gauze dressing regarding the effect on ulcer cleansing and healing processes, experience of pain and the consumption of nursing time, in a controlled, randomized and partially single-blind study with parallel groups of long-stay patients with pressure sores. After a few weeks' treatment the relative decrease in ulcer areas with time was larger in the group treated with the hydrocolloid dressing. The difference was almost statistically significant at week 5 (p = 0.054) and definite at week 6 (p = 0.006). At week 6 the median remaining ulcer area in per cent of the initial area was 0% in the hydrocolloid dressing group and 31% in the group treated with saline gauze (p = 0.016). Analysis of the healing distribution function showed the hydrocolloid dressing to be more effective, although the overall difference was non-significant (p = 0.15). Care of the pressure sore took significantly less time with hydrocolloid dressings.

Aged↗
PubMed1987

Pharmacokinetics of free and total flucloxacillin in newborn infants.

Flucloxacillin 50 mg/kg b.w. was administered intravenously (in combination with ampicillin/gentamicin) and orally (with amoxicillin) to 9 newborn infants (gestational age 33-41 weeks) to treat bacterial infections. The concentrations of flucloxacillin in plasma and urine after i.v. injection were analysed according to an open two-compartment model, and the plasma protein binding of flucloxacillin and its distribution to blood cells and plasma water in whole blood were determined. Considerable differences were found from values reported in adults. The terminal half-life averaged 4 h 38 min and was significantly correlated with gestational age. Plasma clearance was low (0.744 ml X min-1 X kg-1), due to the small renal clearance (0.182 ml X min-1 X kg-1), whilst non-renal clearance (0.563 ml X min-1 X kg-1) was approximately the same as in adults. The mean apparent volume of distribution of total drug (Vz) was 0.280 l/kg. The corresponding volume of distribution of unbound drug (Vu1 + Vu2) was 1.74 l/kg, which indicates considerable extravascular drug binding. The plasma protein binding of flucloxacillin (mean 86.3%) was significantly correlated with gestational age and the bilirubin/albumin concentration ratio. Bioavailability after oral administration, when corrected for changes in terminal half-life, was 47.7%, which is only slightly lower than that reported in adults. Since the plasma concentrations after both i.v. and oral administration were well above the MIC-values generally reported for Staphylococcus aureus, and since few side-effects were observed, intravenous injection or, in selected cases, orl administration of flucloxacillin appears to be a reliable therapy for the treatment of infections due to sensitive strains of S. aureus in premature newborn infants.

Administration, Oral↗
PubMed1987

Comparison of the pharmacokinetics of cephradine and cefazolin in pregnant and non-pregnant women.

The pharmacokinetics of cephradine, a cephalosporin with a low degree of protein binding, was studied in 12 women after oral and intravenous administration of the drug during and after pregnancy. Six of the 12 women also received a cephalosporin with a high degree of protein binding, cefazolin, intravenously during and after pregnancy. For both drugs most pharmacokinetic parameters were altered in pregnancy. The area under the plasma concentration-time curve (AUC) following intravenous administration was smaller for both drugs during as compared to after pregnancy (mean change 39% for cephradine and 31% for cefazolin). Half-lives of both drugs were significantly shorter during compared with after pregnancy (mean change 26% for cephradine and 35% for cefazolin). Consequently, total body clearance was increased during pregnancy. A significant negative correlation between length of gestation and total clearance per kg bodyweight was seen for cephradine. The bioavailability of oral cephradine did not differ significantly during compared with after pregnancy. It is concluded that the dosage of both cefazolin and cephradine should be increased when treating infections in pregnant women in order to obtain the same antibacterial effect as when treating non-pregnant women.

Absorption↗
PubMed1986

Occupational fluoride exposure and plasma fluoride levels in man.

The individual fluoride exposure and the corresponding body fluid levels were studied in 41 workers in an aluminum plant in Sweden. During the shift (8 h) personal air samplings were performed and plasma fluoride levels determined. Pre- and post-shift urine fluoride excretion were also measured. The average total fluoride exposure was 0.91 mg/m3 of which 34% was gaseous fluoride (mean value 0.31 mg/m3). The mean fluoride plasma level before the shift was 23 ng/ml (1.2 microM/l) and increased on average to 48 ng/ml (range 14-151 ng/ml) at the end of the shift. The plasma levels found were in no case remarkably high. There was a high correlation between fluoride renal clearance and urinary flow (r = 0.481; n = 38; P = 0.00232). A high fluid intake during the shift will thus increase the capacity of the kidney to excrete fluoride and decrease the levels of fluoride in the body. There was a significant correlation between the amount of gaseous fluoride and the area under the plasma concentration-time curve (r = 0.459; n = 40; P = 0.0029) and also the amount of fluoride excreted (r = 0.530; n = 40; P = 0.0004). When fluoride exposure and body burden are to be studied on an individual basis these two parameters give better quantitative information and are to be recommended instead of urine fluoride concentration measurements. The prevention of fluoride inhalation by using a safety-mask during the shift was also demonstrated. The workers who used a safety-mask during the whole shift reduced the inhalation of fluoride to 30 to 40% compared to those who did not use any mask.

Adult↗
PubMed1985

Pharmacokinetics and distribution of flucloxacillin in pacemaker patients.

The pharmacokinetics of flucloxacillin in plasma and tissue fluid after i.v. infusion of 1 g was analyzed according to an open two-compartment model in 19 patients with bradyarrhythmias (mean age 70.8 years) admitted for implantation or replacement of a permanent pacemaker system. After the first infusion of flucloxacillin (5 min), the distribution phase was rapid (t 1/2 alpha = 0.13 h). The plasma half-life of elimination (t 1/2 beta) was 1.51 h, which is almost twice as long as reported in healthy volunteers. Total plasma clearance (93.1 ml/min) was also lower than is usually found in healthy individuals, due to low renal clearance of flucloxacillin (60.2 ml/min). The total apparent volume of distribution during the beta-phase (Vdarea) was 0.172 l/kg and distribution in the central compartment (Vc) 0.064 1/kg. In each patient plasma protein binding and drug distribution to plasma water, proteins and blood cells in whole blood were determined. Binding in plasma to proteins was 91.0% and distribution to blood cells in whole blood 13.8%. The mean distribution volume of free flucloxacillin during the beta-phase (Vd beta free) was 2.18 1/kg, which exceeds total body water, suggesting possible intracellular distribution and substantial tissue binding. Plasma concentrations of flucloxacillin after the fourth dose (1 g t.i.d.) were very similar to those obtained after the first infusion and those predicted from the single dose kinetics. The concentration of flucloxacillin in fluid from the pacemaker pockets in 5 patients averaged 12.1 micrograms/ml and 9.5 micrograms/ml at 1 and 5 h, respectively, which was more than ten times the MIC-values for Staphylococcus aureus and S. epidermidis.(ABSTRACT TRUNCATED AT 250 WORDS)

Adult↗
PubMed1983

Renal excretion of fluoride during water diuresis and induced urinary pH-changes in man.

Fluoride renal clearance (CF) was studied in young healthy subjects with standard clearance technique following administration of 3 mg F as a 30-min constant infusion. High urinary flow rates were induced and experiments were performed under both urinary alkaline and acidic conditions. The data showed that a high urinary flow resulted in maximum fluoride clearance. High water diuresis may therefore be an important part in the treatment of acute fluoride intoxication.

Adult↗
PubMed1983

Busulfan kinetics.

Busulfan kinetics were studied in patients with chronic myelocytic leukemia after oral doses of 2, 4, and 6 mg. The plasma concentration-time data could be fitted to a zero-order absorption one-compartment open model. The elimination rate constant averaged 0.27 +/- 0.05 hr-1 (SD). The plasma AUC was linearly related to the dose. The lag time for the start of absorption, the time absorption ends, and the absorption rate constant showed some interindividual variations. About 1% of busulfan is excreted unchanged in urine over 24 hr.

Adult↗
PubMed1983

The relationship between plasma fluoride, urinary excretion rate and urine fluoride concentration in man.

The fluoride concentration in urine is commonly used for monitoring fluoride exposure, e.g., in aluminium plants. Hitherto this parameter does not seem to have been related to the actual fluoride concentration in plasma following fluoride exposure. In the present study the fluoride concentration in urine, the urinary excretion rate of fluoride and the fluoride concentration in plasma have been studied in five volunteers after intake of 10 mg of fluoride in the form of sodium fluoride (NaF) tablets. In pharmacokinetic analyses of the data calculation of the half-life of fluoride from plasma data and from the urinary excretion rate yielded almost identical results; 5.78 hours (plasma) and 5.11 hours (urine). It was found that plasma fluoride levels were correlated with the fluoride concentration in urine (r = .7532; n = 70), but even more with the urinary excretion rate of fluoride (r = .9651; n = 63). The data suggest that plasma fluoride levels or urinary excretion rates of fluoride may give a more correct picture of occupational fluoride exposure than fluoride concentrations in urine.

Adult↗
PubMed1983

Appearance of pethidine and norpethidine in cerebrospinal fluid of man following intramuscular injection of pethidine.

The plasma and cerebrospinal fluid (CSF) concentrations of pethidine and its main metabolite in plasma, norpethidine, were determined in 20 patients undergoing minor surgery who had received pethidine chloride as premedication in a standard dose of 100 mg intramuscularly. The disposition of pethidine and norpethidine in plasma was followed for 3-8 h after administration. The rate of transfer of the drug and its metabolite from plasma to CSF was assessed on the basis of a single sample of CSF taken from each patient. Pethidine appeared within less than 18 min in the CSF, reaching a maximum after about 90 min. After that, the pethidine concentration ratio CSF/plasma was relatively stable at 0.4-0.5. This is in agreement with the concept that the concentration of a drug in CSF is correlated with the concentration of unbound drug in plasma at equilibrium. Norpethidine which was present in rapidly increasing concentrations in plasma after a delay of 30 min, appeared in CSF in a slower and more erratic fashion as compared to the parent compound. However, after 240 min, the CSF/plasma concentration ratio was similar for pethidine and norpethidine. Thus, transfer from plasma to CSF occurs relatively rapidly. There is little evidence for a functionally significant blood-brain barrier for pethidine and norpethidine.

Adult↗
PubMed1983

Drug binding to plasma proteins during human pregnancy and in the perinatal period. Studies on cloxacillin and alprenolol.

Plasma protein binding of one acidic drug, cloxacillin, and one basic drug, alprenolol, was determined by equilibrium dialysis at +37 degrees C during pregnancy and the 1st postnatal week in 12 women and their newborn infants and in 7 nonpregnant women (controls). A significant increase in fraction free cloxacillin in maternal plasma occurred during pregnancy already from the 2nd trimester compared to the controls (p less than 0.01) and was most pronounced at delivery (median values 0.126 and 0.069, respectively). A similarly increased fraction free cloxacillin was found in cord blood (median value 0.108) which further increased during the 1st postnatal week (range 0.112-0.164). In maternal plasma the binding capacity returned to the values of the controls during the same time period. The binding of cloxacillin was significantly correlated with the concentration of albumin (p less than 0.01). High correlation was also found between binding of the basic drug alprenolol and concentration of orosomucoid (p less than 0.005). This was most obvious in the newborn infants with low concentrations (range 0.1-0.3 g/l) and in the mothers during the puerperium with high concentrations of orosomucoid (range 0.7-2.5 g/l). On the basis of plasma protein binding data in the mother and her child, a maternal to fetal plasma concentration ratio was calculated. For cloxacillin this ratio was close to unity (1.03), while it was significantly above unity for alprenolol (1.72). At equilibrium, therefore, the total plasma concentration of alprenolol in the mother can be expected to exceed the concentration in her infant.

Adolescent↗
PubMed1982

Prolactin response following intravenous and oral sulpiride in healthy human subjects in relation to sulpiride concentrations.

Sulpiride (100 mg) was administered intravenously and orally to healthy human subjects. Serum concentrations of sulpiride and prolactin were followed for 36 h. Both routes of drug administration resulted in a pronounced and sustained increase in serum prolactin concentration. The prolactin response was positively correlated to the prolactin baseline value. The concentrations of prolactin remained at an elevated plateau for 9--36 h after drug treatment despite low drug concentrations. The level of this plateau was directly related to the normal circadian secretion of prolactin. The sustained prolactin elevation may be due to high affinity and strong binding of the compound to the regulating receptors or the formation of an active sulpiride metabolite. Prolactin and sulpiride concentrations were significantly correlated during the initial phase after intravenous sulpiride. Following intravenous and oral sulpiride the area under the concentration-time curve (AUC) for prolactin was similar despite a considerable difference in the sulpiride concentration.

Administration, Oral↗
PubMed1982

Comparative disposition of pethidine and norpethidine in old and young patients.

Pethidine was given as a single intravenous dose for premedication before minor surgery. Two groups of subjects were studied, old patients aged more than 65 years, and young patients aged 18-30 years. Blood samples were taken at fixed intervals for 30 h after the injection, and the plasma concentrations of pethidine and its major metabolite norpethidine were analyzed by gas chromatography. In comparison with the young the old patients had a lower plasma clearance for pethidine (9.13 +/- 2.50 versus 16.18 +/- 5.15 ml/min/kg), slower elimination rate beta (0.101 +/- 0.036 versus 0.211 +/- 0.146), and a larger AUC (1935 +/- 554 versus 1092 +/- 277 h . ng/ml) but a similar volume of distribution (5.69 +/- 1.54 versus 5.38 +/- 1.75 l/kg). Norpethidine appeared later and reached its peak concentration later in the old patients than in the young. In several old patients it was still present at a plateau level after 30 h. The present study emphasizes that both parent drug and active metabolite must be taken into consideration when drug therapy is evaluated. The data do not provide pharmacokinetic support for a reduction in the dose of pethidine if it is given as a single intravenous dose. However, when repeatedly administered, it is advisable to reduce the total daily dose.

Adolescent↗
PubMed1982

Drug distribution in whole blood of mothers and their newborn infants: studies of cloxacillin and flucloxacillin.

The distribution of cloxacillin and flucloxacillin in whole blood from seven newborn infants and their mothers was determined in vitro by equilibrium dialysis at 37 degrees C. Seven healthy, non-pregnant women of reproductive age served as controls. The distribution of the penicillins to erythrocytes was the same in the infants as in the adults. It was significantly lower in the presence of plasma albumin than when plasma was replaced by isotonic phosphate buffer. The plasma protein binding of cloxacillin and flucloxacillin in 22 infants was significantly lower than in the controls, but was slightly higher than in the mothers. A significant correlation between binding of cloxacillin and flucloxacillin in the same individual suggested that the two drugs were bound to similar sites. During the first postnatal week binding in infant plasma decreased. This change was correlated with an increase in the bilirubin levels. In the mothers, the binding increased during the first week after delivery. On the basis of the distribution data, maternal to fetal plasma and whole blood concentration ratios at equilibrium were calculated. These ratios were lower for flucloxacillin (medians 0.770 and 0.821, respectively) than for cloxacillin 0.996 and 1.094). Accordingly, at equilibrium somewhat higher levels of flucloxacillin should appear on the fetal than on the maternal side, whereas the concentrations of cloxacillin would be expected to be approximately the same.

Blood Proteins↗
PubMed1982

Pethidine binding to blood cells and plasma proteins in old and young subjects.

The distribution of 3H-pethidine in whole blood was compared in old (63-86 years; n = 11) and young (19-25 years, n = 12) subjects using equilibrium dialysis. The plasma protein binding was 52.7 +/- 3.3% (mean +/- SD) in the old subjects and 51.8 +/- 3.1% in the young: the difference was not statistically significant. Studies on isolated plasma protein fractions showed that the main pethidine-binding protein was alpha 1-acid glycoprotein. Accordingly, the degree of pethidine binding is likely to be affected by inflammatory disease rather than by age. The distribution of pethidine to blood cells showed no age-related difference; the ratio between whole blood and plasma concentrations was 0.99 in old and 0.98 in young subjects. In whole blood from old and young subjects, 43% and 41% of pethidine was present in erythrocytes, 27% and 26% in plasma water whereas 30% and 29% was bound to plasma proteins. The mean ratio between pethidine in cells and plasma water (2.01) indicates binding of the drug in or on the blood cells. These in vitro results do not support the previous theory that a decrease in intracellular pethidine distribution in old age was the reason for the reported higher plasma levels. A slower elimination rate remains the most likely explanation for the increased plasma concentration of pethidine in old patients.

Adult↗
PubMed1982

Renal clearance of fluoride in a steady state condition in man: influence of urinary flow and pH changes by diet.

In order to study fluoride renal clearance, four subjects were given 3 mg fluoride as sodium fluoride tablets every 6 hrs for 60 hrs during two separate periods - during production of acid urine induced by a protein rich diet and during production of alkaline urine obtained by giving a vegetarian diet. Plasma and urine were collected every third hour for 72 hours during each experiment. In the protein rich diet period urinary pH was significantly lower than when the subjects were maintained on the vegetarian diet. Lower urinary output of fluoride during the protein rich diet experiment was recorded, however, the difference was not significant. Plasma fluoride at steady state was almost the same during both experiments. Renal fluoride clearance was significantly correlated to urinary pH in both types of experiments. When renal fluoride clearance was plotted versus urinary flow, the correlation was only significant during alkaline conditions. The average renal clearance was not significantly different between the two sets of experiments. It may be concluded, that pH and diuresis both influences fluoride renal clearance. Moreover, the results suggests that dietary components as such, influence renal clearance of fluoride in some way or another.

Adult↗