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Biomedical subjects

P Crome

Publications and source records attributed to P Crome.

At least 55 records · Page 3Linked to original sources

Pharmacokinetics of dextropropoxyphene and nordextropropoxyphene in young and elderly volunteers after single and multiple dextropropoxyphene dosage.

1. The pharmacokinetics of dextropropoxyphene (D) and nordextropropoxyphene (ND) have been studied in 12 healthy young (21-28 years) and 12 healthy elderly (70-79 years) male and female subjects. Each received 65 mg D and plasma D and ND concentrations were measured by h.p.l.c. with electrochemical detection for up to 7 days and again after 65 mg D, 3 times daily for 1 week. 2. There were no significant differences in median D and ND half-life, AUC, Cmax and tmax between the male and female subjects in either group. Within the groups the mean D half-life (h) was longer in the young after multiple dosing (mean +/- s.d.:13.2 +/- 5.2 and 23.7 +/- 11.3, P less than 0.05, paired t-test) but there were no other significant differences. 3. Between the groups, the median single and multiple dose D and ND half-lives were all significantly longer (P less than 0.02) and the median D AUC for both single and multiple doses was significantly higher (P less than 0.01 and P less than 0.05, respectively, Mann-Whitney U-tests) in the elderly. 4. There was no relation between multiple dose Cmax and other parameters such as single dose D half-life. However, across the groups D and ND half-lives after both single and multiple dosage correlated significantly with estimated creatinine clearance, the correlation being strongest with ND (r = -0.76 and -0.84, respectively).

Adult↗

Plasma nitrendipine concentrations in elderly normotensive volunteers after single and multiple dosing.

An acute and chronic dosing pharmacokinetic study of the calcium antagonist nitrendipine was carried out in 8 normotensive volunteers (mean age 80.1 +/- 3.4 years) to investigate if drug accumulation occurred in the elderly. Subjects received 10 mg nitrendipine once daily by mouth for 8 days. Plasma nitrendipine concentrations before administration and at 0.5, 1, 2, 4, 6 and 8 hours after dosing were measured after the first and last dose. Comparison of the pharmacokinetic data from Days 1 and 8 failed to show any evidence of nitrendipine accumulation in these elderly subjects.

Aged↗

Clinical pharmacokinetic considerations in the elderly. An update.

There are numerous studies of drug handling in the elderly, but it is difficult to assess the significance of changes seen in vitro, or after single-dose administration, because they are often compensated by other mechanisms at steady-state. However, a knowledge of these studies is important as the results alert the investigator to possible treatment problems. The high incidence of adverse drug reaction in the elderly population leaves no doubt that improvements in therapy are needed. Research has been directed at seeking patterns of abnormality in the elderly on which to base recommendations for alterations in dosage regimens. The major shortcoming of this approach has been the failure to distinguish between the effect of chronological age on drug pharmacokinetics, and drug kinetics in elderly people with multiple pathology. The latter concern appreciates the variety of factors involved and the importance of treating each patient as an individual: presentation of mean data is confusing and misleading. The objective of drug treatment in any age group, but particularly in the elderly, is to administer the smallest possible dose which gives adequate therapeutic benefit throughout the entire dosage interval with the minimum of side effects. For most drugs the safe starting dose in the elderly is one-third to half that recommended in the young. Vigilance for potential side effects with plasma concentration monitoring, if available, should help keep toxicity to a minimum. When other medications are added or changed, the possibility of interaction should be anticipated. Methods for individualisation of dosage regimens and the use of sustained-release formulations in the elderly are discussed. Dosage alteration in the elderly in terms of reduced dose frequency, rather than dose size, may help improve compliance. A knowledge of the pharmacokinetics of a drug helps determine which approach will be most beneficial.

Age Factors↗

Pharmacokinetics of flupirtine in elderly volunteers and in patients with moderate renal impairment.

The pharmacokinetics of flupirtine after a single oral dose of 100mg have been studied in patients with moderate renal impairment and in healthy elderly subjects aged 66-83 years. Mean elimination half-life of flupirtine was higher in elderly patients than in younger normal subjects, and this was associated with an increased maximum serum concentration and reduced clearance. The mean half-life in patients with renal impairment was higher than in normal subjects. There was no correlation between observed elimination half-life and degree of renal impairment, but the creatinine clearance of most patients fell in a narrow range between 43 and 60 ml/min. In the light of these results and until further information is available, it would be prudent to start treatment of patients who are elderly or have evidence of renal impairment with half the dose of flupirtine recommended for younger patients with normal renal function.

Age Factors↗

Chlortenoxicam pharmacokinetics in young and elderly human volunteers.

The pharmacokinetics of chlortenoxicam, a new non-steroidal anti-inflammatory drug, have been compared in young and elderly healthy human volunteers. Chlortenoxicam was found to have a relatively short mean elimination half-life of about 4 hours, with considerable inter-subject variability, but there was no significant difference between young and elderly subjects. There was no evidence of accumulation with repeated administration. No unchanged chlortenoxicam was found in urine from any subject, suggesting that it undergoes extensive metabolism in man.

Adult↗

Pharmacokinetics of phenylethylmalonamide (PEMA) in elderly men.

The pharmacokinetics of phenylethylmalonamide (PEMA) were studied in 6 elderly men after oral administration of a single 400 mg dose. Peak PEMA serum levels were obtained within 4 h of intake, half-life values ranged from 30.7-57.9 h in these elderly men. The elimination half-life was twice as long when compared to a study previously performed in young volunteers.

Aged↗

Influence of age, sex and body weight on the dapsone acetylation phenotype.

The acetylation of dapsone (DDS) was determined by estimation of the ratio of monoacetyldapsone (MADDS) to DDS concentrations in plasma following a single dose of DDS in 337 white British subjects (193 female; 144 male). The percentage of slow DDS acetylators in the whole group was 60.3%. There was no statistically significant difference in this proportion between 191 elderly subjects (age greater than 65 years) and 143 young subjects (age less than 30 years). Although there was a small (66.3%) but significant (P = 0.033) preponderance of slow acetylators in the young male group there was no difference in the distribution of acetylator phenotypes between the sexes among either the elderly group or in the whole population studied. No correlation was found between absolute body weight and MADDS/DDS ratios.

Acetylation↗

Bed blocking in Bromley.

A point prevalence survey of all acute beds in the Bromley district found that more than one in 10 patients were classified by their doctors as bed blockers (one in five in the medical wards). There were appreciable clinical and demographic differences distinguishing bed blockers from patients whose stay had been prolonged and who were judged as still requiring acute beds. Social and administrative problems also contributed to bed blocking so that further action by geriatricians, psychogeriatricians, and social workers was required to reduce the numbers. A substantial proportion of bed blockers, however, were highly dependent and could be transferred only to long stay wards or nursing homes. Bed blocking seems inevitable in wards that are attempting to cope with the steadily increasing proportion of elderly patients according to traditional models of acute care.

Age Factors↗

Comparison of pharmacokinetic profiles of single and multiple doses of a slow release Oros oxprenolol delivery system in young normotensive and elderly hypertensive subjects.

Oxprenolol in an Oros 8/130 sustained release osmotic pump system (equivalent to 120 mg oxprenolol hydrochloride in a conventional formulation and releasing 8 mg h-1) was given to eight normal young subjects (mean age 23 years) and eight elderly hypertensive patients (mean age 77 years). The plasma concentration-time profiles of oxprenolol were determined over 32 h using gas liquid chromatography after the initial dose and following seven doses. The elderly patients had a significantly higher AUC and maximum plasma oxprenolol concentration following both the first and final doses studied. It is unlikely that this difference is due to a prolonged absorption phase in the elderly patients. Reduced drug clearance seems the most probable explanation.

Adult↗

Pharmacokinetic profile of controlled release ketoprofen in elderly patients.

The pharmacokinetics of ketoprofen following the administration of the first and final dose of a controlled release formulation (200 mg ketoprofen) once daily for 10 days to nine elderly patients have been studied. Plasma ketoprofen concentrations were measured by h.p.l.c. The data were compared to previously reported studies in young male volunteers. Mean +/- s.d. peak plasma concentrations (5.6 +/- 1.75 micrograms ml-1 and 6.3 +/- 2.7 micrograms ml-1 on day 1 and day 10, respectively) were higher than those reported in young volunteers given similar treatment, but similar to those reported in young volunteers following 50 mg four times daily of conventionally formulated ketoprofen, and markedly lower than reported following a single 100 mg dose of ketoprofen. The half-life for drug release (mean +/- s.d.) from the controlled release formulation (8.5 +/- 7.4 h) and accumulation upon repeated dosing (28%) were essentially the same as reported for young volunteers. The area under the plasma concentration-time curve was about 65% greater than reported in young volunteers following administration of controlled release ketoprofen. This increase in exposure to ketoprofen is probably partly due to the lower volume of distribution in the elderly and partly due to a reduced renal excretion of the glucuronide metabolite of ketoprofen. It was concluded that controlled release ketoprofen may be administered in standard doses (200 mg once daily) to elderly patients whose elimination processes are not severely impaired (i.e. severe renal failure or hepatic disease).(ABSTRACT TRUNCATED AT 250 WORDS)

Aged↗

Digoxin and cimetidine: investigation of the potential for a drug interaction.

The potential for a pharmacokinetic interaction between digoxin and cimetidine was investigated in a series of studies. In a single-dose cross-over study in healthy volunteer subjects cimetidine increased the area under the plasma digoxin concentration curve and the peak plasma digoxin concentration. In a repeated-dose study in healthy volunteer subjects taking digoxin 0.25 mg daily, co-administration of cimetidine resulted in an average increase in plasma digoxin concentration of 0.15 ng/ml. In a repeated-dose study in healthy volunteer subjects taking digoxin 0.5 mg daily, co-administration of cimetidine resulted in an average increase in plasma digoxin concentration of 0.19 ng/ml. In a repeated-dose study in patients receiving long-term digoxin therapy for atrial fibrillation co-administration of cimetidine had no significant effect on plasma digoxin concentrations. We have shown that co-administration of cimetidine and digoxin in volunteer subjects causes a statistically significant but small increase in plasma digoxin concentration but no such increase was found in patients. We conclude that it is doubtful that this interaction is of any clinical significance.

Adult↗

Pharmacokinetics of dextropropoxyphene and nordextropropoxyphene in elderly hospital patients after single and multiple doses of distalgesic. Preliminary analysis of results.

The plasma elimination half-life of dextropropoxyphene and its metabolite nordextropropoxyphene was investigated in seven elderly hospital patients after the administration of both single and multiple doses of Distalgesic. The mean elimination half-life of dextropropoxyphene after multiple dosing was 35.7 h (range 24.0-50.6 h) and the mean half-life of nordextropropoxyphene was 53.3 h (range 25.1-76.3 h). The half-lives of both dextropropoxyphene and nordextropropoxyphene are much longer than those reported by other investigators in younger subjects.

Acetaminophen↗

Activated charcoal in tricyclic antidepressant poisoning: pilot controlled clinical trial.

1 A randomised clinical trial was carried out to assess the effects of activated charcoal in the management of suspected tricyclic antidepressant poisoning. 2 Forty-eight patients entered the study, twenty receiving supportive care plus activated charcoal (10 g) and twenty-eight supportive care alone. 3 Drug screening showed that only seventeen patients had taken tricyclic antidepressants alone. 4 Activated charcoal had no effect on either the rate of lightening of coma or the fall in plasma antidepressant concentration in the 'pure' tricyclic antidepressant poisoning group. 5 No serious side-effects of activated charcoal were reported.

Adolescent↗

In vitro and in vivo evaluation of two preparations of activated charcoal as adsorbents of aspirin.

1 The adsorptive capacities of two preparations of activated charcoal have been studied both in vitro and in vivo using aspirin as a test compound. 2 The in vitro adsorptive capacities of the charcoal preparations were 477 mg of acetylsalicylic acid/g effervescent charcoal ('Medicoal'); 359 mg/g untreated standard charcoal ('Norit-A') and 482 mg/g reheated charcoal ('Norit A'). 3 In vivo both charcoal preparations significantly reduced peak salicylate concentrations and salicylate availability, to a similar extent (analysis of variance P less than 0.001). 4 Both charcoal preparations have similar capacities for adsorbing aspirin both in vitro and in vivo.

Adsorption↗