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Biomedical subjects

I R Edwards

Publications and source records attributed to I R Edwards.

At least 73 records · Page 4Linked to original sources
PubMed1988

Pharmacokinetics and sputum penetration of enoxacin after twice daily oral dosing for seven days.

The ability of enoxacin to penetrate into sputum and its distribution and elimination characteristics after dosing to steady state were determined in six subjects with permanent tracheostomies. At steady state the mean trough level of enoxacin in sputum was 1.75 +/- 0.70 mg/kg (mean +/- S.D.), and the corresponding level in plasma was 1.23 +/- 0.32 mg/l. The mean peak sputum concentration at steady state was 7.12 +/- 4.21 mg/kg with the corresponding level in plasma being 4.54 +/- 1.34 mg/l. The ratio of the mean trough concentration of enoxacin in sputum to that in plasma was 1.42 +/- 0.36, and the ratio of the mean peak concentrations was 1.67 +/- 1.07. The pharmacokinetics of enoxacin in sputum were similar to those in plasma, the only significant difference being between the mean times to reach peak concentration (T-max) which were 2.62 +/- 1.04 and 0.92 +/- 0.44 h in sputum and plasma respectively (P less than 0.01). After reaching steady state, the mean area under the plasma time-concentration curve (AUC) from 0 to 12 h (the dosing interval) was 26.6 +/- 5.9 mg/h/l, and the mean AUC (0-12) for sputum was 40.9 +/- 21.8 mg/h/kg. The mean apparent total clearance was 259.6 +/- 48.8 ml/min and the mean apparent volume of distribution was 169.6 +/- 30.51. Enoxacin exhibits a high degree of penetration into sputum which may prove useful in the treatment of bacterial infections of the respiratory tract.

Administration, Oral↗
PubMed1987

Cough associated with captopril and enalapril.

Thirty three reports of cough associated with captopril and 26 associated with enalapril received by the New Zealand intensive medicines monitoring programme were reviewed. The programme is a specialised part of the New Zealand postmarketing surveillance system. Review of these reports showed that the cough was an adverse reaction to the drugs, occurred even with low dose treatment, and was severe enough to warrant withdrawal of the drugs in most of the cases reported. A significant sex difference was shown, with women predominating. The reaction seemed to be a greater problem with enalapril, and in seven patients it occurred with both captopril and enalapril. Withdrawal of treatment resulted in rapid recovery, and no long term effects were shown. The pathogenesis of the reaction is unknown, but possible mediators include bradykinin and prostaglandins.

Captopril↗
PubMed1987

Nonlinear pharmacokinetic characteristics of 5-fluorouracil (5-FU) in colorectal cancer patients.

The nonlinear disposition kinetics of 5-fluorouracil (5-FU) were investigated in 6 patients with colorectal carcinoma. Each patient randomly received two single, intravenous doses of 5-FU (7.5 and 15 mg/kg) on separate days. Venous blood and urine samples were collected just prior to and for 5 h after drug administration. In addition to the kinetic studies, the in vitro whole blood/plasma concentration ratio and stability of 5-FU at 37 degrees C were determined in whole blood from normal volunteers and from 5 patients with colorectal carcinoma. A disproportionate increase in area under the curve and corresponding decrease in total body clearance with increasing dose was observed suggesting dose-dependent behavior of 5-FU. Doubling the dose was accompanied by a 36% decrease in nonrenal clearance but no apparent change in renal clearance. Therefore, the mechanism for dose-dependent elimination appears to be primarily associated with nonrenal processes. The mean 5-FU half-life following the high dose was nearly twice as long as that observed for the low dose (12.3 versus 6.2 min). The log-linear decline in plasma concentrations and increase in half-life with dose suggest the potential role of product-inhibition as an explanation for the observed nonlinearity in 5-FU elimination. The present study demonstrates that 5-FU degrades when incubated in whole blood. This most likely reflects metabolism in red blood cells or other blood-formed elements since 5-FU was stable in plasma. Although degradation in whole blood occurs, the estimated whole blood clearance does not contribute significantly to the observed total body clearance value. The findings suggest the possibility of pulmonary clearance of 5-FU.

Adult↗
PubMed1987

The effect of age on the pharmacokinetics of enoxacin.

We have studied the pharmacokinetics of enoxacin in two groups of subjects, 10 young (18-45 years) and 10 elderly adults (greater than 65 years) after a single oral dose of enoxacin (600 mg). Enoxacin was absorbed rapidly, peak plasma concentrations being reached within two hours in both groups. However, the peak plasma concentration of enoxacin was significantly higher in the elderly than in the young adults. The area under the concentration-time curve extrapolated to infinity was also significantly greater in the elderly compared with the young subjects, and the apparent renal clearance was significantly less in the elderly than in the young adults. Consequently, the urinary elimination of unchanged enoxacin was significantly reduced in the elderly. The apparent volume of distribution in the elderly was significantly less than in the young adults. The elimination half-time of enoxacin was similar in the two groups.

Adult↗
PubMed1987

Captopril: 4 years of post marketing surveillance of all patients in New Zealand.

The Intensive Medicines Monitoring Programme (IMP), a specialised part of the New Zealand Post Marketing Surveillance system, has been used to monitor captopril since it was first approved for marketing for the treatment of hypertension and heart failure. Monitoring has consisted of (1) spontaneous reporting for which doctors have been encouraged to report all clinical events, (2) a specific event recording survey at the end of the first year and (3) a controlled patient survey of taste disturbance. The IMP gathers prescription information on about 85% of all patients. There were 4,124 patients at the end of the first 4 years. Reported events involved 4% of patients, the majority being cutaneous (1%) and gastrointestinal (0.7%). The event recording survey gave an overall rate of adverse events of 2.2 per patient year. The taste survey showed a remarkably high incidence of taste disturbance in the control population and only taste loss was significantly higher (P less than 0.01) for captopril. This ongoing study has so far demonstrated a low incidence of adverse effects due to captopril, which is reassuring in view of its increasing use for mild hypertension and early cardiac failure.

Adolescent↗
PubMed1986

Distribution of Pt in the urine and kidney of the cisplatin treated rat.

The urinary and renal distribution of Pt following the administration of cis-dichlorodiammine platinum II (cisplatin) to adult male Wistar rats was studied by gel filtration and ion exchange chromatography. Several low molecular weight (LMW) Pt-containing fractions with the same chromatographic properties as those found in urine incubated with cisplatin are present in the kidney cytosol within 15 min of the administration of cisplatin. The concentration of Pt in these fractions decreases rapidly and after 4 h most of the Pt in the kidney cytosol is in a high molecular weight (HMW) fraction which contains 2 subfractions. The smaller fraction (mol. wt. = 20 000), but not the larger (mol. wt greater than 250 000), is also present in the urine of the cisplatin-treated rat, but neither fraction is present in urine incubated with cisplatin and neither is formed by the interaction of cisplatin or the urinary LMW Pt-containing fractions with kidney cytosol in vitro. It is suggested that the smaller fraction may be derived from the filtration and reabsorption of plasma protein-bound Pt, whereas the larger fraction is more likely to be formed exclusively within the kidney cell.

Animals↗
PubMed1986

Time course of the binding of platinum to subfractions of the kidney cytosol in the cisplatin-treated rat.

In male rats treated with cis-dichlorodiammine platinum II (cisplatin, 5 mg/kg, s.c.), the accumulation of Pt in the kidneys occurred in two phases. Total renal Pt content peaked after 15 min and decreased rapidly, then increased to a second peak after 48 hr and thereafter decreased slowly during the next 6 days. Sephadex G-50 chromatography showed that in the kidney cytosol Pt was located in three subfractions; a high molecular weight (HMW) fraction (relative elution volume, Vr = 0.9-1.2), a heterogeneous low molecular weight (LMW) Pt-binding fraction (Vr = 1.2-2.2) and a LMW complex fraction (Vr = 2.2-2.7). Initially, most of the Pt was located in the HMW- and LMW complex fractions and the initial loss of Pt from the cytosol occurred from the latter fraction. In contrast, during the second phase much of the additional Pt accumulated in the LMW Pt-binding fraction, the Pt content of which paralleled that in the whole kidney. It is suggested that the LMW Pt-binding fraction may play a significant role in the accumulation and retention of Pt and may provide a site of detoxification during the second phase of influx of Pt into the kidneys.

Animals↗
PubMed1986

Post-marketing surveillance in New Zealand.

In early 1977, the Intensive Medicines Monitoring Programme (IMP) was instigated for selected medicines with novel chemistry or pharmacology and those expected to be widely used. Pharmacists are requested to record the patient and prescribing doctor's details along with the medicine dose and duration of the prescription. Doctors are asked to send details of any unexpected clinical events. Doctors' spontaneous returns are low and have been supplemented by regular surveys. Now a new self-carboned prescription form has recently been introduced upon which doctors indicate if events have occurred. Since trial introduction of the new system the rate of event reporting in the test areas has increased 15-fold. In view of this, the duplicate prescription system will be introduced to the whole country over the next 3 years. In the past, the IMP has been used to follow up signals of new adverse events, to establish adverse drug reaction profiles and to establish risk-benefit indications.

Evaluation Studies as Topic↗
PubMed1985

Analysis of 5'-deoxy-5-fluorouridine and 5-fluorouracil in human plasma and urine by high-performance liquid chromatography.

A relatively simple and sensitive high-performance liquid chromatographic (HPLC) method is described for measuring the two anticancer drugs 5'-deoxy-5-fluorouridine (5'dFUR) and 5-fluorouracil (5-FU) in human plasma and urine. The procedure for plasma includes solvent extraction using ethyl acetate-isopropyl alcohol (85:15) followed by silica gel column chromatography to separate these compounds from constituents normally occurring in plasma. The analysis by reversed-phase HPLC is performed on a phenyl column using an aqueous mobile phase with ultraviolet detection (280 nm). The overall recovery from plasma was 61% and 65% for 5'dFUR and 5-FU, respectively. The sensitivity limit of the assay for both compounds was 50 ng/ml of plasma. Analysis of these compounds in urine did not require the silica column chromatography isolation step.

Chromatography, High Pressure Liquid↗
PubMed1985

Mianserin.

Explore the source record for details and available documents.

Agranulocytosis↗
PubMed1985

Factors affecting the kinetics of two benzothiazine non-steroidal anti-inflammatory medicines, piroxicam and isoxicam.

The pharmacokinetics of isoxicam and piroxicam were compared in 12 young adults (less than 40 years) and 12 elderly subjects (greater than 65 years). After a single oral dose of 200 mg isoxicam or 20 mg piroxicam blood samples were taken for 168 h and the plasma drug concentrations determined by HPLC. The elimination half life of piroxicam for the adults was 57.1 +/- 16.4 h (mean +/- SD; harmonic mean 52.9 h) and for the elderly subjects was 57.8 +/- 22.1 h (harmonic mean 52.1 h). The corresponding values after isoxicam were 34.3 +/- 13.6 h (harmonic mean 31.6) for the adults and 39.1 +/- 22.7 h (harmonic mean 33.5) for the elderly subjects. Similarly no differences were noted in either the AUC0-infinity after piroxicam (adults 154.1 +/- 52.2 micrograms . h/ml, elderly 163.6 +/- 99.1 micrograms . h/ml) and isoxicam (adults 642.7 +/- 241.9 micrograms . h/ml, elderly 787.9 +/- 613.1 micrograms . h/ml) or the apparent oral clearance of piroxicam (adults 2.39 +/- 0.80 ml/min, elderly 2.51 +/- 0.90 ml/min) and isoxicam (adults 5.84 +/- 2.04 ml/min, elderly 5.59 +/- 2.12 ml/min). One adult and two elderly subjects exhibited slower elimination of both medicines than the remainder of each group. However determination of the oxidation phenotype using sparteine metabolism showed that this was not a likely determinant of the reduced clearance.

Adolescent↗