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Biomedical subjects

M Orme

Publications and source records attributed to M Orme.

At least 19 recordsLinked to original sources
PubMed1991

Oral contraceptive steroids--pharmacological issues of interest to the prescribing physician.

Oral contraceptive steroids (OCS) are well absorbed from the gastrointestinal tract in humans. However, while the progestogens are almost completely bioavailable, ethinylestradiol (EE2) is subject to extensive first pass metabolism consisting chiefly of conjugation with sulfate in the gut wall. Both EE2 and progestogens are well absorbed in patients with an ileostomy or with diseases such as cystic fibrosis or Crohn's disease. However in patients with celiac disease (gluten-sensitive enteropathy) the gut wall is less able to conjugate EE2 and thus its bioavailability is increased. The bioavailability returns to control values as the disease is improved following gluten withdrawal. Other drugs that are conjugated with sulfate, such as vitamin C and paracetamol, compete for available sulfate when coadministered with OCS leading to high plasma levels of EE2. Enzyme-inducing agents such as rifampicin, phenobarbitone, phenytoin and carbamazepine reduce blood levels of the OCS leading to contraceptive failure. In the case of anticonvulsants (but not rifampicin) this can be easily overcome by increasing the dose of OCS used. Broad-spectrum antibiotics are reported to cause failure of contraception by interfering with the enterohepatic circulation of EE2 but limited systematic studies show no evidence of such an interaction. Nevertheless practitioners are advised to recommend the use of alternative contraceptive precautions for women receiving broad-spectrum antibiotics concurrently with their OCS preparation.

Anti-Bacterial Agents↗
PubMed1991

The pharmacokinetics of ethynylestradiol in the presence and absence of gestodene and desogestrel.

Single doses of ethynylestradiol (30 micrograms) were given alone and in combination with either gestodene (75 micrograms) or desogestrel (150 micrograms) to 10 healthy female volunteers. The doses of steroids were given both orally and by i.v. infusion over 5-7 minutes. Blood samples were taken at regular intervals over 24 hours. The area under the plasma concentration versus time curve (AUC) for oral EE2 alone was 867 +/- 338 pg/ml x h, for oral EE2 in the presence of gestodene it was 795 +/- 206 pg/ml x h and for oral EE2 in the presence of desogestrel it was 614 +/- 132 pg/ml x h. With either gestodene or desogestrel present, the AUC of EE2 was not significantly different from that found when EE2 was given alone. In addition, there was no significant difference between EE2 + gestodene and EE2 + desogestrel. Comparing the relative oral and iv doses, the bioavailability of EE2 (alone) was 59.0 +/- 13% (n = 6), for EE2 plus gestodene it was 62.1 +/- 10% and for EE2 in the presence of desogestrel it was 62.1 +/- 4.4%. The clearance of EE2 (alone) was 19.9 +/- 5.5 l/h and in the presence of gestodene it was 19.4 +/- 9.6 l/h. The clearance of EE2 in the presence of desogestrel appeared slightly greater at 27.7 +/- 8.9 l/h but none of these clearance values were significantly different from each other. The urinary excretion of 6-beta-hydroxy cortisol was similar after all 6 doses of EE2. These data strongly suggest that following single dose administration, neither gestodene nor desogestrel have any inhibitory effect on the metabolism of EE2 or alter its kinetics to any clinically significant extent.

Administration, Oral↗
PubMed1991

The lack of interaction between temafloxacin and combined oral contraceptive steroids.

In view of the considerable debate concerning the possible failure of contraception in women taking broad spectrum antibiotics, we have examined a group of 12 women aged 22-32 in a controlled study. Each woman had been on long-term therapy with oral contraceptive steroids (OCS) containing ethynylestradiol (EE2) and levonorgestrel (Ng) for at least 6 months and all were in good general health. Blood samples were taken about 11.0 hours after dosing with their OCS on days 5, 6, 7 and 8 of their contraceptive cycle, for measurement of EE2, Ng, FSH and LH by radioimmunoassay. In addition blood samples were taken on days 19, 20 and 21 of the contraceptive cycle for assay of progesterone concentrations in plasma. The study was repeated in the next cycle of use of their OCS during which they took temafloxacin, a broad spectrum quinolone antibiotic in a dose of 600 mg twice daily for 7 days starting on day 1 of the cycle. All women completed the study satisfactorily as judged by diary cards, tablet counts and plasma temafloxacin concentrations. In the early part of the study some nausea and headaches were seen due to taking temafloxacin on an empty stomach but these effects were not seen when the antibiotic was later given with food. There was no evidence of any interaction between temafloxacin and the OCS. The plasma concentration of EE2 was 61.4 +/- 21.1 pg/ml in the control cycle and 68.5 +/- 26.6 pg/ml in the temafloxacin cycle.(ABSTRACT TRUNCATED AT 250 WORDS)

4-Quinolones↗
PubMed1990

The teaching and organisation of clinical pharmacology in European medical schools (W.H.O. Working Group on Clinical Pharmacology).

A World Health Organisation (European Regional Office) working party has been established to review the progress of clinical pharmacology in European countries. As part of this review a questionnaire on the teaching of clinical pharmacology was sent to the Deans of all 350 medical schools in the region. Very few replies were received from U.S.S.R., Greece and Portugal and these countries' returns were not analysed further. The overall compliance rate (excluding these countries) was 82% with a figure of 84% from Western Europe and 74% from Eastern Europe. An average time of 96 h (range 0-320) was devoted to pharmacology teaching in the medical curriculum in Western Europe with 124 (0-240) h in Eastern Europe. In contrast 28 h (0-210) was devoted to clinical pharmacology teaching in Western Europe and 27 h (0-90) in Eastern Europe. On average in Western Europe each medical school had 2 individuals trained in clinical pharmacology with 1.3 posts in the subject and the figures for Eastern Europe were 2.3 and 1.1 respectively. However these figures hide a wide variance in the teaching of clinical pharmacology. Particularly in Western Europe there are a number of medical schools in Italy, Spain and the Federal Republic of Germany (FRG) where clinical pharmacology is not taught and there is a dearth of individuals trained in the subject. Every effort to encourage clinical pharmacology and its teaching should be made, particularly in these countries.

Curriculum↗
PubMed1990

Clinical pharmacology and primary health care in Europe--a gap to bridge. The WHO Working Group on Clinical Pharmacology in Europe.

A group of senior European clinical pharmacologists presents a position paper on the possible role of clinical pharmacology (CP) in bridging the gap between academic drug evaluation and drug prescribing in primary health care (PHC). As a teaching, research and service discipline CP has developed in academic or other major hospitals while 80% of all drugs are prescribed in PHC. CP therefore has to extend its functions to PHC. Examples are given of how joint ventures between clinical pharmacologists and PHC physicians may improve the quality of drug research and increase the clinical relevance of drug information in PHC, thereby contributing towards rational drug utilization in PHC. Colleagues in PHC are invited to respond to this call for collaboration.

Drug Prescriptions↗
PubMed1990

The interaction of phenytoin and carbamazepine with combined oral contraceptive steroids.

Patients taking oral contraceptive steroids (OCS) are known to suffer contraceptive failure while taking anticonvulsants such as phenobarbitone, phenytoin and carbamazepine. We have studied the single dose kinetics of ethinyloestradiol (EE2); 50 micrograms, and levonorgestrel (Ng); 250 micrograms in groups of women before and 8-12 weeks after starting therapy with phenytoin (n = 6) and carbamazepine (n = 4). The area under the plasma concentration-time curve (AUC) was measured over a 24 h period for each steroid and significant reductions were seen with both anticonvulsants. Phenytoin reduced the AUC for EE2 from 806 +/- 50 (mean +/- s.d.) to 411 +/- 132 pg ml-1 h (P less than 0.05) and for Ng from 33.6 +/- 7.8 to 19.5 +/- 3.8 ng ml-1 h (P less than 0.05). Carbamazepine reduced the AUC for EE2 from 1163 +/- 466 to 672 +/- 211 pg ml-1 h (P less than 0.05) and for Ng from 22.9 +/- 9.4 to 13.8 +/- 5.8 ng ml-1 h (P less than 0.05). These changes are compatible with the known enzyme inducing effects of phenytoin and carbamazepine. Patients taking these anticonvulsants will need to be given increased doses of OCS (equivalent to 50-100 micrograms EE2 daily) to achieve adequate contraceptive effects.

Adolescent↗
PubMed1990

Adverse effects of captopril in hospital outpatients with hypertension.

Hypertensive patients prescribed captopril while attending a hospital hypertension clinic were studied, to identify the benefits of the drug, its adverse effects and factors predisposing to them. One hundred and eighty two patients were followed for a mean of 18 months; 24 received captopril alone, and 158 combinations of captopril and other antihypertensive drugs, especially loop diuretics (91/158), or thiazide diuretics (57/158), or other vasodilators (57/158). The mean final dose of captopril was 67 mg/day. Blood pressure (BP) was effectively controlled in 73% of patients (mean fall in systolic BP 29 mmHg, CI 24 to 34, P less than or equal to 0.001; mean fall in diastolic BP 18 mmHg, CI 16 to 20, P less than or equal to 0.001). Blood urea and creatinine rose slightly in all patients (urea by 0.9 mmol/l [13%], CI 0.5-1.3, P less than or equal to 0.001 and creatinine by 9 mumols/l [8%], CI 4-13, P less than or equal to 0.001). Twenty six patients were withdrawn from captopril therapy: 6 because of poor control of their blood pressure, two because it was no longer necessary and 12 (7.7%) because of extrarenal adverse effects--10 for rashes, one each for gastric upset and impotence. Captopril was withdrawn in a further 6 patients, because of deteriorating renal function. Factors discriminating those at risk of renal dysfunction were high doses of captopril, concomitant high dose diuretic therapy and undiagnosed renovascular disease.

Adult↗
PubMed1990

The chemotherapy of onchocerciasis. XIV. Studies with mebendazole citrate.

Twenty patients from an area of vector control in the savannah region of northern Ghana with moderate to heavy infection with Onchocerca volvulus were randomised to receive two priming doses of levamisole 150 mg on two occasions followed either by mebendazole-citrate (500 mg) given daily or twice daily for 14 days. The two dose levels produced a similar effect on skin microfilariae (80-88% reduction) with a very mild systemic clinical reaction: low levels were maintained over 42 weeks. Both regimes were embryotoxic for O. volvulus; an effect which was transient in the single dose group but persisted for more than three months in the twice daily dose group. Mebendazole-citrate appeared to be absorbed more predictably than has been observed previously for mebendazole. The degree of systemic exposure as determined by measurement of AUC (0-24 h) was 2.5 times greater for the twice daily dose as compared to the single dose and this fact was reflected in the efficacy of the two dose regimes against the adult female worms at three months.

Adult↗
PubMed1989

The teaching of clinical pharmacology in Europe and North America.

A recent survey conducted under the auspices of the WHO shows that on average in European medical schools only 28 hours of teaching are devoted to clinical pharmacology, whereas over 100 hours are devoted to pharmacology. In many schools no clinical pharmacology is taught, and there is a lack of trained individuals and posts in clinical pharmacology. In North America there is a similar lack of clinical pharmacology teaching.

Europe↗
PubMed1989

Healthy volunteer studies in Great Britain: the results of a survey into 12 months activity in this field.

1. A survey has been conducted amongst 459 members of the Clinical Section of the British Pharmacological Society to ascertain facts about the administration of drugs to healthy volunteers over the period October 1986 to September 1987. 2. A response rate of 87.1% was obtained with 114 individuals being involved in healthy volunteer studies. After exclusion of duplicate returns from the same unit 98 questionnaires were analysed. 3. Drugs were given in the year under review to 8163 healthy volunteers for research purposes. Minor adverse effects were reported in 565 (6.9%), moderately severe adverse effects in 45 (0.55%) and potentially life threatening adverse effects in 3 (0.04%). No lasting sequelae were reported. 4. Drugs were given to 7607 healthy student volunteers as part of class teaching practicals. Minor adverse effects were reported in 6.0% of student exposures but no moderately severe or life threatening adverse effects were reported. 5. The risk involved in healthy volunteer studies is very small indeed but some suggestions are made as a result of the questionnaire to improve further the safety of these studies.

Drug Evaluation↗
PubMed1987

The disposition of amodiaquine in man after oral administration.

A method is described for the simultaneous determination of amodiaquine (AQ) and desethylamodiaquine (AQm) in plasma, urine, whole blood and packed red cells. After oral administration of AQ (600 mg) to seven healthy subjects, absorption of AQ was rapid, reaching peak concentrations in plasma, whole blood, and packed cells at 0.5 +/- 0.03, 0.5 +/- 0.1 and 0.5 +/- 0.1 h respectively (mean +/- s.e. mean). The apparent terminal half-life of AQ was 5.2 +/- 1.7 h. AQ was detectable for no longer than 8 h. AQ underwent rapid conversion to AQm, which reached peak concentrations in plasma, whole blood and packed cells at 3.4 +/- 0.8, 2.3 +/- 0.5 and 3.6 +/- 1.1 h respectively. AQm was still detectable at the end of the sampling period (96 h) when the plasma concentration was 29 +/- 8 ng ml-1. The area under the plasma concentration vs time curve (AUC(0, infinity] for AQ was 154 +/- 38 ng ml-1 h; the corresponding value for AQm was 8037 +/- 1383 ng ml-1 h. There were no significant differences in the values for AUC of AQ between plasma, whole blood, or packed cells. The whole blood to plasma concentration ratio for AQm was 3.1 +/- 0.2, and the AUC (0.24) for AQm in whole blood (6811 +/- 752 ng ml-1 h) was significantly greater than that in plasma (2304 +/- 371 ng ml-1 h), P less than 0.001. The recovery of AQm from urine collected 0-24 h was 6.8 +/- 0.8 mg (n = 6).(ABSTRACT TRUNCATED AT 250 WORDS)

Administration, Oral↗