Pharmacokinetics of intranasal drug administration: the influence of some biological factors.
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Administration, Intranasal↗
Biomedical subjects
F Larsen
Publications and source records attributed to F Larsen.
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↗
The effect of the CCK receptor antagonist CR 1409 on bile reflux pancreatitis in the opossum.
Availability of specific cholecystokinin (CCK) receptor antagonists has the potential for contributing to delineation of the role of CCK in the development of pancreatitis and, perhaps, development of new therapeutic agents for treatment of the disorder. The purpose of this study was to evaluate the effect of a potent CCK receptor antagonist, CR 1409, on bile reflux pancreatitis. The opossum pancreatic duct enters the common duct in such a position that it is possible to ligate the common duct distal to the pancreatic duct, resulting in bile refluxing into the pancreatic duct and producing pancreatitis. CR 1409 was administered to opossums at the time of distal common duct ligation and at the time of cystic- and common ducts ligations. In a separate group, CR 1409 administration was begun 24 hours following onset of pancreatitis. Control experiments were performed, in which CR-1409 was not administered. Serum amylase, pancreas gland weights, inflammation, and systemic venous insulin, glucagon, and CCK concentrations were evaluated. Bile duct ligation resulted in significant hyperamylasemia, pancreas gland edema, inflammation, hyperglucagonemia, hypercholecystokinemia, and hypoinsulinemia. CR 1409, administered at the onset of pancreatitis, significantly decreased amylase concentrations, gland weight, and inflammation, when compared to control values. Hormonal changes associated with pancreatitis were also significantly altered by CR 1409 administration. When administered 24 hours following onset of pancreatitis, CR 1409 was not effective in altering the pancreatitis produced by bile duct ligation. The results suggest that CCK plays a permissive or contributory role in the inflammatory process and in associated hormonal changes during development of bile reflux pancreatitis in the opossum.
Amylases↗
Influence of concentration and injection volume on the bioavailability of subcutaneous growth hormone: comparison of administration by ordinary syringe and by injection pen.
In order to study whether the bioavailability of subcutaneously injected growth hormone (GH) is dependent on the concentration/volume injected, the relative GH bioavailability was evaluated in 14 GH-deficient patients. In a cross-over study the patients received, in random order two separate subcutaneous GH injections (Norditropin) 4 IU administered by means of an ordinary syringe (4 IU ml) and an injection pen with cartridge (Nordiject 24) (12 IU/ml). Blood samples were drawn over a 14 hr period and assayed for serum concentrations of GH and IGF-I. The mean value (+/- S.D.) of the relative absorption fraction (Fpen/sy) was 1.09 +/- 0.39. Mean values of Cmax were 8.6 ng/ml +/- 4.8 and 8.3 ng/ml +/- 7.5 for syringe and pen respectively. Corresponding values for Tmax were 311 min. +/- 131 for syringe and 309 min. +/- 104 for pen. Although a considerable interindividual variation was seen, the relative absorption fraction did not differ significantly from 1 (2 P = 0.78). Further there was no significant difference in neither Cmax (2 P = 0.39) nor Tmax (2 P = 0.55). IGF-I serum profiles tended to be higher following syringe compared to pen injection (2 P = 0.054). On the basis of this study we conclude that in this dosage regimen. GH bioavailability following pen injection equals that of injection by syringe (i.e. no effect of a three fold increase/decrease in GH concentration/volume respectively).
Adult↗
Rapid and simple preparation of plasmids suitable for dideoxy DNA sequencing and other purposes.
Plasmid DNA released from bacteria by boiling in the presence of lysozyme and Triton x-100 and without further purification can be sequenced by the dideoxy method using T7 DNA polymerase, when conditions during alkali denaturation and subsequent ethanol precipitation are adjusted to remove contaminants. The samples remain in the same microcentrifuge tubes from the harvesting of the bacteria until the splitting of the sample into four aliquots for the termination reactions. Less background label is observed with end-labelled primers (radioactivity or fluorescence), but even when radioactive nucleotides are incorporated during the sequencing reactions, 250 bases or more can be read from template prepared from 1.5 ml bacterial culture. The DNA can also be cut by restriction enzymes; the purification procedure described thus provides the rapid preparation of plasmids for a variety of purposes.
Base Sequence↗
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↗
Psychosocial function before and after gastric banding surgery for morbid obesity. A prospective psychiatric study.
UNLABELLED: The objective of this study was to measure psychosocial functioning in morbid obese patients before and after horizontal gastric banding surgery, and to analyse the relations between the changes in psychosocial functioning and preoperative variables and degree of weight loss. METHODS: One hundred and three patients undergoing horizontal gastric banding surgery from 1982-85 were personally interviewed and rated by the author on DSM-III axis 1, 2 and 5, the CPRS, demographic data and precoded clinical scales. The interviews and ratings were completed in the last week before the operation. In addition the patients completed questionnaires concerning psychic symptoms (SCL-90) and quality of life. Twenty-five patients also completed the questionnaires six months before the operation. The patients were followed up after one and three years. RESULTS: There were 66 women and 24 men with a mean age of 35.4 years. Their mean preoperative weight was 121.8 kg corresponding to a Broca Index of 1.72 and a Body Mass Index of 41.5. They had a mean SCL-90/GSI score of 0.99. Fourty-one percent got a diagnosis on DSM-III axis 1 and 22% a diagnosis on axis 2. Thirty-seven percent had made at least one contact with health services before the operation due to psychiatric problems. There were no strong relations between the relative preoperative weight and any other preoperative variable. The follow-up rate was 93%. The patients had a mean weight loss of 34.9 kg after one year and 31.5 kg three years after the operation. On group level the course and outcome of psychosocial functioning was a beneficial one. These changes were highly statistically significant and evident after one year, with only slight differences to the three years follow-up. The degree of weight loss explained a modest but statistically significant part of the variance in most of the psychosocial outcome variables when the preoperative level of the variable and the preoperative weight were controlled for. The degree of psychiatric contact in the follow-up period seemed to reflect another dimension. It was not related to the changes in the other psychosocial outcome variables, nor to the degree of weight loss, but was highly correlated to the degree of preoperative psychiatric contact. A group of patients with negative psychosocial outcome was identified. This group was characterized by a higher frequency of preoperative psychiatric help-seeking, than the rest of the patients. This pattern was most evident in a subgroup of 19% of the patients, who had a negative psychosocial reaction in spite of a sufficient weight loss.(ABSTRACT TRUNCATED AT 400 WORDS)
Adult↗
Personality changes after gastric banding surgery for morbid obesity. A prospective study.
89 morbidly obese patients completed the Basic Character Inventory before and 1 and 3 years after horizontal gastric banding surgery. The aim of the study was to compare preoperative scores of personality traits with those of a normal population, and to examine any change in scores on the different personality traits at the follow-up tests. There was a uniform tendency to higher scores on the Oral cluster traits (Self-doubt, Insecurity, Sensitivity, Dependence, Compliance and Emotional instability) among the patients compared to normals. There was a general significant decrease in the post-operative scores on the Oral cluster traits present already at the 1 year follow-up, most pronounced for Self-doubt, Insecurity and Sensitivity. On the other hand there was a significant increase in the postoperative scores on the Obsessive traits: Parsimony and Orderliness. As a group these patients did not show any adverse changes in their personality traits, on the contrary they seemed less neurotic and possibly exerted more control of their situation after the operation and weight loss.
Adult↗
Plasma concentrations of bromazepam following peroral and sublingual administration.
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Administration, Oral↗
Comparison between personality disorder diagnoses in DSM-III and DSM-III-R: reliability, diagnostic overlap, predictive validity.
97 nonpsychotic consecutive day patients were diagnosed by the axis 1 and 2 in the DSM-III and DSM-III-R system, and their treatment response during their stay was measured by the Health Sickness Rating Scale. The interrater reliability was equally good for both diagnostic systems. On axis 1, there were only minor differences between DSM-III and DSM-III-R. On axis 2, the frequency of schizotypal disorder was reduced by 40% and the frequency of histrionic disorder by two-thirds. The number of schizoid disorders increased from zero to five. Of the DSM-III schizotypals who lost this diagnosis in DSM-III-R (n = 8), 4 got a new diagnosis of schizoid personality and 4 maintained their borderline diagnoses. In DSM-III-R there was a sharper demarcation between patients with severe and nonsevere personality disorder with regard to treatment outcome, indicating an increased validity of these categories. There was also a sharper demarcation between borderline versus histrionic and schizotypal, and between schizotypal and schizoid diagnoses.
Adult↗
Bilateral giant hydroureteronephrosis--a case report with a review of the literature.
Giant hydronephrosis and hydroureteronephrosis are rare conditions, but must be kept in mind in especially children and in young-to-middle-aged adults with long-standing, often symptomless, enlargement of the abdomen. A case of bilateral giant hydroureteronephrosis due to calculi in the ureters is reported. Despite renal insufficiency the patient denied any treatment, but survived 42 months after the primary diagnosis. For diagnostic purposes intravenous pyelography, ultrasonography and computerized tomography are preferable. Supplementary ante- and retrograde pyelography is valuable in locating stenosis or calculi.
Female↗
Organic brain syndrome and long-term exposure to toluene: a clinical, psychiatric study of vocationally active printing workers.
This study addresses the prevalence of organic brain syndrome (OBS) among long-term toluene-exposed rotagravure workers who are still working. The prevalence of OBS in 22 workers exposed to toluene for a minimum of 12 years and 19 unexposed control subjects, matched for age and employment status, was assessed with a comprehensive clinical psychiatric interview. There was a significantly greater prevalence of mild chronic encephalopathy and organic affective syndrome in the toluene-exposed group.
Adult↗
Pharmacokinetics of midazolam and alpha-hydroxy-midazolam following rectal and intravenous administration.
1. In an open cross-over trial, plasma concentrations of midazolam were measured in eight healthy male volunteers following administration of 0.3 mg kg-1 body weight given by the rectal and intravenous routes. 2. Maximum plasma concentrations of 92-156 ng ml-1 (mean 118 ng ml-1) were recorded from 20 to 50 min (mean 31 min) after rectal application. The rectal bioavailability was 40-65% (mean 52%) and the terminal half-life was 114-305 min (mean 161 min). 3. A substantial first-pass hepatic effect was observed following rectal administration. 4. No systemic or local intolerance was noted. 5. In conclusion, the rectal route of administration provides a rapid and reliable absorption of midazolam.
Administration, Rectal↗
[A compulsory course in psychiatry. An evaluation of the theoretical and practical aspects].
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Education, Medical↗
The isolation and characterisation of a cDNA clone for human lecithin:cholesterol acyl transferase and its use to analyse the genes in patients with LCAT deficiency and fish eye disease.
We have isolated cDNA clones coding for human lecithin:cholesterol acyl transferase (LCAT) from a liver-specific cDNA library by the use of two oligonucleotide probes based on the protein sequence. The clones span the sequence coding for the entire secreted LCAT, the 3' untranslated sequence and 12 amino acids of the signal peptide. The peptide sequence contains the conserved active site of serine lipases within a hydrophobic domain, flanked by a possible amphipatic alpha-helix. Only one gene for LCAT could be detected in genomic blots. We have used the cDNA as a probe to analyse the LCAT gene in patients suffering from LCAT deficiency and fish eye disease. No rearrangements or abnormal gene fragments were detected in these patients.
Amino Acid Sequence↗
Interrater reliability of the DSM-III diagnoses in two Norwegian studies on psychiatric and super obese patients.
Two Norwegian psychiatrists classified independently according to DSM-III, 45 patients drawn at random from two populations: one of psychiatric patients (N = 161) and one of super obese surgical patients (N = 71). They interviewed the patients and listened to each other's audio-taped interviews afterwards. In the total group, on axis I the overall agreement was 78 percent (kappa = 0.74). On axis II, the overall agreement was 81 percent (kappa = 0.68). The study shows that by using the DSM-III, two Norwegian psychiatrists obtained good diagnostic reliability.
Adult↗
Experiences with the DSM-III in a psychiatric consultation/liaison service.
375 patients referred to consultation/liaison service at a general hospital from the neurological and internal medical department were diagnosed according to the DSM-III criteria for axis I and II. The sample represents all the patients referred from the two departments in a two year period. The phenomenological approach of the DSM-III and its reliability, is an advantage over older classification systems in the psychiatric consultation/liaison work. The system was easily applicable in this setting, leaving only 4 percent with "Diagnoses deferred" on both axes. From the consultation/liaison psychiatrist's point of view, special problems seemed to exist concerning the categories "Somatoform disorders" and "Psychological factors affecting physical condition", and the concepts of the axis II.
Adjustment Disorders↗
Influence of furosemide and body posture on transthoracic electrical impedance in AMI.
Transthoracic electrical impedance (TEI) is related to thoracic fluid content. In order to analyze this relation, we studied the acute effects of changes in body posture and of intravenous administration of furosemide on TEI in patients with different diuretic regimens. The TEI was measured using a tetrapolar electrode system, and a 100 microA constant current at 100 kHz. The measurements were performed repeatedly during the first two days in 15 consecutive patients with acute myocardial infarction (AMI) and without overt left heart failure, as evaluated from clinical data and bedside catheterization. It was concluded that TEI appears to be a sensitive, noninvasive means of evaluating changes in thoracic fluid content in AMI.
Body Water↗