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PubMed1987

Plasma levels and pharmacokinetics of single and multiple dose of tetrazepam in healthy volunteers.

The pharmacokinetics of tetrazepam (Myolastan, Musaril), were studied in 12 healthy volunteers. Tetrazepam was given orally as a single dose of 50 mg and repeated administration for 5 consecutive days of 50 mg at 12-h intervals, in tablet form. Tetrazepam was measured in plasma using a selective and sensitive GLC method. Tetrazepam is rapidly absorbed after oral administration with a peak plasma level of 0.49 +/- 0.10 mg/l at 0.94 +/- 0.47 h. The drug is widely distributed in the organism with an apparent volume of distribution of 6.7 +/- 2.1 l/kg. Tetrazepam is eliminated with a half-life of 22 +/- 4 h and can be classified as a benzodiazepine with medium half-life value. This medium half-life is the result of the high hepatic clearance of the drug in spite of its large distribution volume. Since in this study 6 male and 6 female volunteers were studied it was possible to compare the pharmacokinetic profile in the two groups. No significant differences were observed. No differences were observed between the pharmacokinetic values after a single dose or after repeated administration.

Administration, Oral↗
PubMed1995

The impact of rheumatoid arthritis on life activities.

OBJECTIVE: To examine the proportion of valued activities performed by persons with rheumatoid arthritis (RA) and the change in this proportion over a 5-year period and to compare the performance and loss of valued activities of persons with and without RA. METHODS: Data were drawn from a longitudinal panel study of persons with RA. Valued activities were assessed using a standardized questionnaire. RESULTS: Over a 5-year period, persons with RA lost approximately 10% of the activities they had valued. Losses were noted in every domain of activity. The greatest losses were seen in work-related, service, nurturant, cultural and leisure, and social participation activities. Compared to persons without arthritis, persons with RA performed fewer valued activities at baseline, and lost more valued activities over the 5-year period. CONCLUSIONS: RA takes a considerable toll on the ability of people with the disease to perform valued life activities. Other research has shown that the loss of valued activities is a strong risk factor for the development of depressive symptoms among women with RA.

Activities of Daily Living↗
PubMed1984

Biotransformation and pharmacokinetics of tetrazepam in man.

The pharmacokinetics and the metabolism of tetrazepam (Musaril) were studied in 12 healthy volunteers. Tetrazepam was given orally as a single dose of 50 mg in tablet form (commercially available formulation). Tetrazepam and nortetrazepam were measured in serum using a selective and sensitive HPLC method. Urinary metabolites were identified after acid hydrolysis and thin-layer chromatographic separation. Tetrazepam is rapidly absorbed after oral administration with a lag-time of 0.45 +/- 0.10 h and reaches a peak serum level of 0.57 +/- 0.06 mg/l at 1.92 +/- 0.19 h after administration. The drug is largely distributed in the organism with an apparent volume of distribution of 225 +/- 40 l. The substitution of the phenyl moiety in the 5-position by a cyclohexenyl ring results in a different metabolism when compared to other benzodiazepines. This different metabolic pathway is the reason why only very small levels of active metabolites are present in serum. Therefore it seems reasonable, at least from the pharmacokinetic point of view, to attribute pharmacologic activity of tetrazepam mainly to the parent drug. Tetrazepam is eliminated with a half-life of 14.9 +/- 4.4 h and can be classified as a benzodiazepine with medium half-life value. This medium half-life is the result of the high hepatic clearance of the drug in spite of its large distribution volume. Since in this study 6 male and 6 female volunteers were studied it was possible to compare the pharmacokinetic profile in the two groups. No significant differences were observed.

Adult↗
PubMed1992

Commentary on "Quantifying the value of human life.

... In his article, "Quantifying the value of human life for cost accounting of safeguards," L. Eugene Arnold proposes a cost-benefit analysis to address three allocation issues concerning the very expensive program of blood monitoring proposed by Sandoz at the time it placed Clozaril...on the American market.... It is important to realize that the use of seemingly value-free procedures to arrive at answers to ethically complex questions does not eliminate the values that underlie the choice of variables to be analyzed. The analyses employed by the author to three ethical questions illustrate this point very well....

Clozapine↗
PubMed1995

Species specific pharmacokinetics of rolitetracycline.

Comparative studies on some selected pharmacokinetic parameters of rolitetracycline (effective antimicrobial activity levels) in sheep, pigs, rabbits, chickens and pigeons were carried out after intravenous administration of the drug at a dose of 5 mg/kg. The results revealed that a two-compartment open model was usually optimal. Interspecies differences in the rate (alpha) and the volume of distribution (Vda), the area under the serum concentration time curve (AUC) and the total body clearance (ClB) were small. The values of the elimination half-life (t1/2 beta) found in sheep, pigs, rabbits, chickens and pigeons were 1.51, 3.06, 2.18, 4.33 and 2.51 h respectively. These results and data in mice, rabbits and man taken from literature were analysed to determine any correlation to body mass (W). The log of the elimination half-life values (log t1/2 beta) of rolitetetracycline revealed a significant correlation with log values of (W) between animal species. This relationship was described by the equation t1/2 beta = 1.27.W0.29 (r = 0.93, P < 0.01, n = 5) for mammal species and t1/2 beta = 1.81.W0.24 (r = 0.78, P < 0.05, n = 7) for mammal and bird species.

Animals↗
PubMed1990

The pharmacokinetics of cotinine in plasma and saliva from non-smoking healthy volunteers.

Cotinine is a major metabolite of nicotine in man. Its disposition kinetics has been followed in plasma and saliva from nine nonsmokers, 23 to 56 years of age. Cotinine 5, 10 and 20 mg was given intravenously and orally to each subject, and plasma, saliva and urine samples were collected for 96 h. The kinetics of cotinine was best described by a multicompartment model with three distinct phases both in plasma and saliva. Regardless of the mode of administration, there was no indication of dose-dependent kinetics. Mean total plasma clearance was 63.8 ml.h-1.kg-1 and mean renal clearance was 4.7 ml.h-1.kg-1, i.e. only 10% of the dose was excreted unchanged in the urine. The volume of distribution, as calculated from the plasma curves, was slightly greater than the body weight, 1.1 l.kg-1. The concentration of cotinine was 20 to 40% higher in unstimulated mixed saliva than in plasma during the absorption, distribution and elimination phases. As the clearance and distribution values in saliva were directly proportional to the corresponding values in plasma, similar terminal half-life values were obtained in the two body fluids, 15.5 and 16.8 h for plasma and saliva, respectively. Thus the kinetics of cotinine is linear after intravenous and after oral dosing, and salivary concentrations give the same information about cotinine disposition in the body as do plasma concentrations.

Adult↗
PubMed2001

To resuscitate or not: a dilemma in terminal cancer care.

One of the difficult dilemmas in terminal care is the decision on whether to start or withhold cardiopulmonary resuscitation (CPR). Is this decision made on purely medical grounds, or is it also influenced by the physician's personal characteristics or education? The aim of this study was to look at factors affecting this decision. A questionnaire was sent out to a stratified sample of 1180 Finnish doctors. The response rate was 62%. The physicians were asked whether they would (a) start CPR or (b) withhold CPR in a scenario describing the unexpected death of a young terminal cancer patient. Data were also collected on demographics, post-graduate training, experience of terminal care, general life values and attitudes, and experiences of severe illness in the family. The proportion of surgeons, internists, GPs and oncologists who said they would have started CPR was 16, 10, 19 and 14%, respectively. Among physicians aged under 35 years, from 35 to 49 years and over 49 years, the proportions of physicians choosing active CPR were 29, 14 and 13%, respectively (P<0.001). As for those with personal experience of terminal care, 13% indicated they would have started CPR compared with 23% of those who had no experience (P<0.01). Those who made a decision in favour of CPR showed a significantly (P<0.001) more negative attitude to withdrawing life-sustaining treatment and valued length of life to a much greater extent (P<0.01).

Adult↗
PubMed1992

Down-regulation and recycling of the nitrobenzylthioinosine-sensitive nucleoside transporter in cultured chromaffin cells.

The dynamics of the nitrobenzylthioinosine (NBTI)-sensitive nucleoside transporter were studied in cultured chromaffin cells. Photolabelling of transporters with [3H]NBTI induced a down-regulation of this protein from the plasma membrane with a half-life value of 2.31 +/- 0.61 h, measured by specific isolation of plasma membrane on polycationic beads. In this internalization step 50-60% of transporters were destroyed. The remaining labelled protein reappeared in plasma membranes and underwent a new disappearance cycle with a longer half-life period (34.65 +/- 3.9 h). A similar pattern of internalization and reappearance of nucleoside transporters was observed in cells cross-linked with non-labelled NBTI, with a half value of reappearance of 33 h. Chromaffin cells cultured in the presence of the protein synthesis inhibitor, cycloheximide, had a component of disappearance for NBTI binding sites with a half-life value of 24.6 +/- 1.4 h.

Affinity Labels↗
PubMed1994

Assessment of coping with muscular dystrophy: a methodological evaluation.

There is no published research on coping with muscular dystrophy among adults. In the present study, two questionnaires, the Reaction to the Diagnosis of Cancer Questionnaire (RDCQ) and the Mental Adjustment to Cancer scale (MAC), were modified in order to measure coping with muscular dystrophy (MD). A total of 60 people (16-64 years) with diagnosed MD answered the questionnaires in two interviews including semi-structured questions. The replies to these questions were analysed by two independent judges on the basis of the RDCQ and MAC categories for coping. The purpose was twofold: to investigate if cancer-coping categories could be used for the classification of interview answers concerning coping with MD, and to gain knowledge about specific coping with MD. Analysis indicated that 82% of replies to semi-structured questions concerned with emotion/appraisal-focused coping with MD can be described by means of RDCQ and MAC categories. Eight new categories were developed to classify the remaining 18%: Anticipation, Creation of new life values, Minimization, Establishment of control over everyday life, Secretiveness, Fear, Social comparison and Coping with heredity. In addition, 997 replies were classified to represent problem-focused coping. The judges reached good agreement with respect to the proportions of replies in the respective coping categories. However, kappa (kappa) values were within the range of fair to good agreement.

Adaptation, Psychological↗
PubMed1989

[The physical development of infants and young children. 4. Body mass--a longitudinal study].

As a result of a longitudinal study (performed 1979-1982) on the somatic development of 84 male and 91 female children from birth up to the third year of life, values of body mass expressed as distance values, increments, and growth velocity are presented. As compared to earlier investigations made in the G. D. R. and to studies from other countries differences of the dynamics of body mass development have been found: with the exception of the birth weight the body mass tends to be higher during the first six month of life in contrast to previous studies, whereas between the 9th to the 18th month of life lower values of body mass have been measured. Additional differences in the dynamics of body mass development between boys and girls are presented.

Body Height↗
PubMed1991

Stereoselective disposition and metabolism of disopyramide in pediatric patients.

Pharmacokinetics of disopyramide (DP) enantiomers was studied in six pediatric patients, 5 to 12 years old, with arrhythmias after i.v. and p.o. administrations of racemic DP. The enantiomers of DP and its active metabolite, mono-N-dealkyldisopyramide, in plasma and urine were determined using a chiral, high-performance liquid chromatography. Plasma protein binding of DP was measured by ultrafiltration. Because the protein binding of DP was not only concentration-dependent but also stereoselective (i.e., S-DP binds to protein more extensively than R-DP), unbound pharmacokinetic parameters were used for evaluating the kinetic behaviors of DP enantiomers. The pediatric age patients had the mean (+/- S.D.) systemic clearance of 15.0 +/- 3.8 and 12.7 +/- 3.9 ml/min/kg for unbound S- and R-DP, respectively, which were not only stereoselectively different (P less than .05) but also at least about twice greater than the reported normal adult values. The mean postinfusion elimination half-life values for unbound S- and R-DP (2.7 +/- 0.5 and 2.8 +/- 0.4 hr, respectively) in pediatric patients were shorter than those reported from normal adults (approximately equal to 4 to 5 hr). The mean nonrenal (i.e., hepatic) clearance for unbound S- and R-DP (11.1 +/- 4.1 and 8.1 +/- 3.9 ml/min/kg, respectively) were also stereoselectively different (P less than .01) and accounted for approximately equal to 70% of the unbound systemic clearance of the respective enantiomers.(ABSTRACT TRUNCATED AT 250 WORDS)

Administration, Oral↗
PubMedDate not supplied

Student dental hygienists' work values: a measure of an emerging profession?

The purpose of this study was to compare the work values of students in the School of Dental Hygiene and the Faculty of Dentistry at the University of Manitoba, Canada, both with each other, and with national sample of Canadian practitioners in both fields. The study was an outgrowth of a larger study measuring the work values of graduating students in six faculties selected to represent the occupational classification system of John Holland. The English version of the Canadian form of the Values Scale which measures 20 work and life values, was used in this study. Differences in values found between the student hygienists and practitioners in both dentistry and dental hygiene may indicate a growing desire for professional status by dental hygienists. Value differences found between practising dentists and hygienists may reflect a traditional hierarchical relationship between these occupations. Limitations of the study and future research questions are discussed.

Adult↗
PubMed1985

Elimination half-life of drugs: value and limitations.

A drug's half-life of elimination from plasma or serum has long been considered a familiar and important pharmacologic property. In fact, elimination half-life has limitations, and its value has been overestimated. Elimination half-life is a dependent variable, related directly to volume of distribution and inversely to clearance. Changes in drug distribution as well as in rate of clearance can alter elimination half-life. Half-life also has limitations as a predictor of a drug's duration of pharmacologic action after single doses, which is related more to distribution than to elimination or clearance. During multiple dosage, elimination half-life does have value in predicting the rate and relative extent of drug accumulation, as well as the rate of washout after termination of treatment. Clinicians should consider volume of distribution and clearance, in addition to elimination half-life, when evaluating the pharmacokinetic properties of drugs.

Half-Life↗
PubMed1981

Pharmacokinetics of metronidazole in patients with enteric disease compared to normal volunteers.

Tablets of 500 mg metronidazole were given to 24 patients with intestinal diseases and to 10 healthy volunteers. The diagnoses included coeliac disease, ulcerative colitis, jejunoileal shunt, ileostomy, and Crohn's disease. Both normal subjects and patients exhibited considerable variation in serum metronidazole concentrations. This applied particularly to the patients who had somewhat slower absorption and later occurrence of serum peaks than did the normal subjects. No major deviation occurred within any of the diagnostic groups. All but the ileostomy patients exhibited a lag before apparent absorption. The individual peaks occurred after 1.5-2.0 h and was 12.7 +/- 2.1 microgram/ml in all disease groups, except the ileostomy patients who exhibited a mean of 16.2 microgram/ml. In the healthy subjects, the mean peak was 12.1 +/- 4.6 microgram/ml. A major finding was the observation that the patients as a group had a higher total area under the serum curves (AUC) than the volunteers. The AUC of normal volunteers was 108.1 microgram . h . ml-1 compared to 260.5 microgram . h. ml-1 in the patients with ileostomy and 147.6 microgram . h . ml-1 for the others. The higher AUC values in the ileostomy group were associated with longer serum half-life values. The serum half-life was 8.3 in the normals, 11.9 with ileostomy and 7.2 h in the remainder. The normal individuals and the patients with ulcerative colitis had higher rates of absorption, those with coeliac disease or ileostomy lower absorption rates than was found elsewhere. The relative volume of distribution (the distribution coefficient) was the same in the healthy individuals as in each patients group, except for the ileostomy patients. The total body clearance was 1.94 liters/h in ileostomy, 3.68 liters/h in the other patients, and 5.43 liters/h in the normal subjects.

Adult↗
PubMed1976

The effect of different oral anticoagulants on diphenylhydantoin (DPH) and tolbutamide metabolism.

The effect of bishydroxycoumarin, phenprocoumon, warfarin and phenindione on the metabolism of diphenylhydantoin (DPH) and tolbutamide has been studied in 54 patients. The half-lives of DPH and tolbutamide in blood following i.v. injections were studied in 33 patients before and after one week of anticoagulant treatment. Bishydroxycoumarin increased the mean half-life values of DPH from 8.8 to 37.4 hours and of tolbutamide from 4.9 to 17.5. Phenprocoumon prolonged DPH half-life from a mean value of 9.9 to 14.0 hours but did not change the tolbutamide half-life. Warfarin and phenindione did not affect DPH or tolbutamide half-lives. Steady state concentration studies in 21 patients showed a rise in serum DPH during bishydroxycoumarin and phenprocoumon treatment but not during treatment with warfarin and phenindione. A rise in serum tolbutamide was noted during treatment with bishydroxycoumarin. These findings suggest that bishydroxycoumarin inhibits the betabolism of DPH and tolbutamide and that phenprocoumon inhibits DPH metabolism. No effect on DPH and tolbutamide metabolism could be demonstrated following administration of warfarin and phenindione.

Coumarins↗
PubMed1998

Pharmacokinetic drug-drug interaction study of delavirdine and indinavir in healthy volunteers.

The potential pharmacokinetic drug-drug interaction between delavirdine, a nonnucleoside analogue reverse transcriptase inhibitor, and indinavir, an inhibitor of HIV protease, was evaluated in healthy volunteers. Subjects received a single 800-mg dose of indinavir sulfate on day 1 (baseline). Delavirdine mesylate 400 mg was administered three times daily on days 2 through 10. On day 9, a single 400-mg dose and on day 10 a single 600-mg dose of indinavir were given along with morning doses of delavirdine. Pharmacokinetic evaluations of indinavir were made on days 1, 9, and 10, and of delavirdine on days 8, 9, and 10. Fourteen healthy male volunteers completed the study. Single doses of indinavir had no clinically important effects on the pharmacokinetics of delavirdine. Mean indinavir Cmax values for the 400-mg and 600-mg doses administered concomitantly with delavirdine were dose proportionally lower than that observed following the 800-mg dose administered alone. Mean Tmax values were similar and ranged from 1.0 +/- 0.3/hour for indinavir 800 mg administered alone to 1.3 +/- 0.4/hour for indinavir 600 mg administered with delavirdine. These results indicate that delavirdine had no clinically important effect on the rate of indinavir absorption. In contrast, the mean indinavir AUC0-infinity, value following the 400-mg dose administered with delavirdine was only 14% lower than the baseline value determined for the 800-mg indinavir dose (25,400 +/- 6960 nM hour versus 29,600 +/- 7920 nM hour), and the mean indinavir AUC0-infinity value for the 600-mg indinavir dose administered with delavirdine (42,700 +/- 9800 nM hour) was 44% greater than the baseline value. All differences among mean AUC0-infinity values were statistically significant. Mean indinavir half-life values were slightly longer when indinavir was given in a dose with delavirdine than when indinavir was administered alone. These results suggest that delavirdine inhibits metabolism of indinavir and support the possibility of a reduction in the magnitude or frequency of indinavir dosage when given in combination with delavirdine.

Administration, Oral↗
PubMed2002

Decision making in terminal care: a survey of finnish doctors' treatment decisions in end-of-life scenarios involving a terminal cancer and a terminal dementia patient.

GOALS: The physicians' decision-making process in terminal care is complex: medical, ethical, legal and psychological aspects are all involved, particularly in critical situations. Here, a study was made of the association of personal background factors with end-of-life decisions. METHODS: A questionnaire was sent to 300 surgeons, 300 internists, 500 health centre practitioners (GPs) and all 82 Finnish oncologists. The response rate was 62%. Two scenarios were presented: one involving a terminal cancer patient, the other a dementia patient. Sociodemographic factors, general life values and attitudes related to end-of-life care were asked. MAIN RESULTS: In the cancer case (Scenario 1) 17%, and in the dementia case (Scenario 2) 43% of all the respondents chose active treatment. In a logistic regression analysis of treatment decisions in Scenario 1, physician's age, specialty, marital status and attitudes to assisted suicide and withdrawal of life-sustaining treatment (LST) entered the model. In Scenario 2, the variables were physician's age, physician's own experience of severe disease in the family, attitude to withdrawal of LST and opinion of advanced directives. CONCLUSIONS: Doctors' end-of-life decisions vary widely according to personal background factors. The findings underline the importance of advance communication, making these decisions in accordance with the patient's wishes.

Adult↗
PubMedDate not supplied

The value and quality of life.

A medical view on 'the value of life' can be inferred from medical accounts of the quality of life: a life has value if it embodies certain qualities. Scales have been developed to quantify quality of life. While the term 'quality of life', is used frequently in everyday discourse, perceptions of what it might actually mean differ greatly and are often incompatible. This incompatibility can be illustrated through an examination and development of the Greek myth of Sisyphus. The different models that the author explores rest on 'significant toil', 'choice', 'happiness or well-being', or 'social factors' being the prerequisite for quality of existence. These models are incommensurable and, as intangible concepts, cannot be quantified. Decision-making in medicine does not require a complex evaluation of quality of life: it consists of the doctor's offer of treatment based on the best evidence, and the patient's consent to, or refusal of, that offer. Apart from the need to obtain consent, the main ethical constraint on the doctor is equity.

Decision Making↗